WEBVTT 00:01.300 --> 00:01.970 J. MICHAEL MCBRIDE: OK, so we've been 00:01.967 --> 00:03.667 talking about electrophilic 00:03.667 --> 00:07.227 addition and the nucleophilic aspect of it. 00:07.233 --> 00:11.203 Today we'll extend that to talk about cycloaddition and 00:11.200 --> 00:13.630 also there'll be some practical applications with 00:13.633 --> 00:19.203 respect to epoxides and acetals and how they work. 00:19.200 --> 00:23.600 So first, about that problem I gave you last time, about 00:23.600 --> 00:26.100 drawing nice curved arrows to show the pinacol 00:26.100 --> 00:27.330 rearrangement. 00:27.333 --> 00:28.973 So, how does it start out? 00:28.967 --> 00:30.727 What's the first thing that happens? 00:30.733 --> 00:35.133 Wells, do you have an idea for acid catalysis here? 00:35.133 --> 00:36.773 What's the very first thing that happens? 00:43.567 --> 00:46.227 Too early in the morning? 00:46.233 --> 00:46.933 Chris, what do you say? 00:46.933 --> 00:48.203 STUDENT: The proton protonates. 00:48.200 --> 00:49.600 PROFESSOR: Protonates what? 00:49.600 --> 00:51.070 STUDENT: Probably OH. 00:51.067 --> 00:53.197 PROFESSOR: OK. 00:53.200 --> 00:57.230 So we'll protonate the OH, and then water can leave. Why is 00:57.233 --> 00:58.573 it good for water to leave, Chris? 00:58.567 --> 01:00.997 STUDENT: The pKa of hydronium is low, 01:01.000 --> 01:03.100 negative. 01:03.100 --> 01:06.200 PROFESSOR: Yeah, O3+ [correction: H3O+] 01:06.200 --> 01:10.070 is good at losing things, how about the other aspect of it? 01:10.067 --> 01:12.597 How about the thing that's leaving, other than the water? 01:12.600 --> 01:13.530 STUDENT: It's charged? 01:13.533 --> 01:15.573 PROFESSOR: Yeah, how about where the charge goes? 01:15.567 --> 01:16.397 STUDENT: Away. 01:16.400 --> 01:20.600 PROFESSOR: What's it going to be when the water leaves? 01:20.600 --> 01:22.200 The water will be neutral. 01:22.200 --> 01:22.470 Pardon me. 01:22.467 --> 01:23.927 STUDENT: It will go from a positive charge to a neutral 01:23.933 --> 01:24.203 charge in this case. 01:24.200 --> 01:27.730 PROFESSOR: The water will, but we care about the organic 01:27.733 --> 01:28.933 thing more than about the water. 01:28.933 --> 01:29.873 What will be left? 01:29.867 --> 01:30.867 STUDENT: Negative charge. 01:30.867 --> 01:33.167 PROFESSOR: No, no. 01:33.167 --> 01:36.927 The thing is a cation, if you lose neutral water, 01:36.933 --> 01:38.773 the charge will stay. 01:38.767 --> 01:39.627 Where will it be? 01:39.633 --> 01:41.403 STUDENT: On the carbon. 01:41.400 --> 01:43.500 PROFESSOR: Is that a good place for it to be? 01:43.500 --> 01:46.670 STUDENT: Yes. 01:46.667 --> 01:47.497 PROFESSOR: Why? 01:47.500 --> 01:48.370 Why is that good? 01:48.367 --> 01:49.197 STUDENT: It's tertiary. 01:49.200 --> 01:51.000 PROFESSOR: It's tertiary. 01:51.000 --> 01:55.330 All right, so we get a nice tertiary cation. 01:55.333 --> 01:59.503 What did anybody think about the next step here? 01:59.500 --> 02:01.200 Yeah, Kate. 02:01.200 --> 02:04.570 STUDENT: I thought that maybe there was a methide shift. 02:04.567 --> 02:06.667 PROFESSOR: A methide shift, good. 02:06.667 --> 02:09.797 So the methide could shift over, a rearrangement, and now 02:09.800 --> 02:11.500 you have this cation. 02:11.500 --> 02:14.600 Now, Kate, you're going to tell me about this cation. 02:14.600 --> 02:18.230 We started already with a very good cation, a tertiary 02:18.233 --> 02:21.903 cation, right, that's as good as they get with-- 02:21.900 --> 02:24.200 unless you have double bonds next door. 02:24.200 --> 02:24.970 OK. 02:24.967 --> 02:26.397 But, what's the driving force? 02:26.400 --> 02:27.800 Why should it go this direction? 02:27.800 --> 02:30.630 What's good about being on the right? 02:30.633 --> 02:37.003 STUDENT: It has to do with the fact the CO 02:37.000 --> 02:41.370 bond is a low LUMO. 02:41.367 --> 02:45.967 PROFESSOR: No, I don't think you could say 02:45.967 --> 02:48.097 the CO, it's true-- 02:48.100 --> 02:51.170 the CO bond is a lower LUMO. 02:51.167 --> 02:54.497 But to the extent that the oxygen, the reason it's low is 02:54.500 --> 02:56.530 because of the oxygen, right. 02:56.533 --> 02:59.033 And, that oxygen is withdrawing charge from the 02:59.033 --> 03:02.803 carbon, withdrawing electrons from the carbon, tending to 03:02.800 --> 03:05.700 make the carbon positive anyhow. 03:05.700 --> 03:09.070 So, if a carbon is already positive, it's not such a 03:09.067 --> 03:11.767 great place to put more positive charge. 03:11.767 --> 03:14.997 So, to the extent that that sigma bond is important, you'd 03:15.000 --> 03:16.370 think it'd go the other direction. 03:16.367 --> 03:19.797 The oxygen would be electron withdrawing and destabilize 03:19.800 --> 03:21.130 the cation. 03:21.133 --> 03:25.133 Can anybody see why it could be good to have 03:25.133 --> 03:26.173 the oxygen next door? 03:26.167 --> 03:28.227 It's certainly not that sigma bond. 03:36.867 --> 03:39.827 STUDENT: Isn't the unshared pair the reason? 03:39.833 --> 03:41.603 PROFESSOR: What about the unshared pair? 03:41.600 --> 03:45.470 STUDENT: They stabilize the positive charge. 03:45.467 --> 03:47.867 PROFESSOR: You know actually, I would say 03:47.867 --> 03:49.467 the other way around. 03:49.467 --> 03:54.297 The electrons are something real, right, and they get 03:54.300 --> 03:58.200 stabilized by mixing with the low vacant orbital that's 03:58.200 --> 04:00.170 associated with the positive charge. 04:00.167 --> 04:02.727 It's the electrons that get lower in energy. 04:02.733 --> 04:04.973 OK, but you're absolutely right, so you can draw a 04:04.967 --> 04:07.497 resonance structure like that, and that's why it's good to go 04:07.500 --> 04:08.930 to the right. 04:08.933 --> 04:10.803 OK, now, how do you get from there to the product? 04:17.333 --> 04:17.773 Jack? 04:17.767 --> 04:20.467 STUDENT: Hydrogen can go off. 04:20.467 --> 04:24.797 PROFESSOR: Yeah, you just lose a proton, right, and you've 04:24.800 --> 04:25.730 got the product. 04:25.733 --> 04:28.203 So, that's the mechanism of the pinacol rearrangement. 04:28.200 --> 04:33.130 It's all steps that you know well, but you have to think 04:33.133 --> 04:34.633 and put them together, so that's just 04:34.633 --> 04:36.603 an exercise in that. 04:36.600 --> 04:40.570 OK, now back to these simultaneous reactions that 04:40.567 --> 04:42.367 are involved in addition to alkenes. 04:42.367 --> 04:46.827 Simultaneous in the sense that there's both electrophile, 04:46.833 --> 04:48.503 which is what they're typically called, 04:48.500 --> 04:51.530 electrophilic additions, but, also a nucleophile that's 04:51.533 --> 04:53.203 participating at the same time. 04:53.200 --> 04:56.600 We saw this last time with dichlorocarbene which you 04:56.600 --> 04:59.970 remember came on edge on, and then rotated in order to make 04:59.967 --> 05:02.967 the two new bonds to give us cyclopropane. 05:02.967 --> 05:06.027 We saw it in hydroboration, where the vacant orbital on 05:06.033 --> 05:12.303 the B attacks, but at the same time the high HOMO B-H, mixes 05:12.300 --> 05:18.430 with the pi-star orbital. 05:18.433 --> 05:22.633 OK, so, now we're going to go on to a different kind of a 05:22.633 --> 05:25.833 way of making a cyclopropane with what's called the 05:25.833 --> 05:30.633 Simmons-Smith reagent, and then into epoxidation, adding 05:30.633 --> 05:33.933 just an oxygen to a double bond to give us 3-membered 05:33.933 --> 05:39.133 oxirane ring, and then ozonolysis which is a more 05:39.133 --> 05:44.333 dramatic kind of cycloaddition to give a ring, and then we 05:44.333 --> 05:48.703 probably won't get today to catalytic hydrogenation, and 05:48.700 --> 05:51.400 to polymerization and metathesis, 05:51.400 --> 05:53.430 where metals are involved. 05:53.433 --> 05:56.473 So, we'll do those others today. 05:56.467 --> 05:59.667 First, the so called Simmons-Smith 05:59.667 --> 06:01.897 reagent or a carbenoid. 06:01.900 --> 06:06.000 We talked about CCl2, a carbene, last time, that's a 06:06.000 --> 06:10.670 free species, it's pretty reactive, but it floats free. 06:10.667 --> 06:12.067 It has an existence. 06:12.067 --> 06:15.197 These are called carbenoids, because they don't really give 06:15.200 --> 06:18.730 a free carbene, but they give a product as if it were a 06:18.733 --> 06:23.873 carbene, that is the CH2 in a 3-membered ring. 06:23.867 --> 06:31.067 The reagents as you can see, are methylene iodide, CH2I2, 06:31.067 --> 06:34.727 and the thing called zinc-copper couple, and I 06:34.733 --> 06:37.003 don't know where the name couple came from except that 06:37.000 --> 06:38.400 there two metals there. 06:38.400 --> 06:41.400 But it, turned out that having a little copper with the zinc 06:41.400 --> 06:42.770 made it work better. 06:42.767 --> 06:46.567 So, I don't know, anyhow, zinc is the operative group here, 06:46.567 --> 06:49.197 but copper clearly has something to do with it. 06:49.200 --> 06:52.900 This was developed at DuPont Central Research in 06:52.900 --> 06:55.370 Wilmington, Delaware, where Howard Simmons was the 06:55.367 --> 06:57.097 Director of Research. 06:57.100 --> 07:00.900 First, a word about metals and alkyl halides. 07:00.900 --> 07:04.270 So, you have a metal and an alkyl halide. 07:04.267 --> 07:07.797 Now, metals tend to be over on the left of the periodic 07:07.800 --> 07:13.170 table, what does that mean about their electrons? 07:13.167 --> 07:16.897 Are the highest valence electrons held tightly or are 07:16.900 --> 07:19.900 they able to give up electrons? 07:19.900 --> 07:21.070 Compared to most things. 07:21.067 --> 07:22.327 Do they have a high HOMO? 07:25.167 --> 07:27.427 Things that are on the left of the periodic table don't have 07:27.433 --> 07:31.203 such a big nuclear charge, given the row they are in, so 07:31.200 --> 07:33.630 they're relatively good at giving up electrons. 07:33.633 --> 07:35.633 How about RX? 07:35.633 --> 07:40.473 What makes it reactive, a halide on R? 07:40.467 --> 07:42.167 What's its characteristic reactivity? 07:42.167 --> 07:42.467 Ayesha. 07:42.467 --> 07:44.597 STUDENT: Low LUMO, sigma-star. 07:44.600 --> 07:47.130 PROFESSOR: Low LUMO, sigma-star. 07:47.133 --> 07:49.503 So, we have something that can give electrons and something 07:49.500 --> 07:52.830 that can take it, so it won't surprise you that you can get 07:52.833 --> 07:56.803 an electronic transfer from the metal, and it's just a 07:56.800 --> 07:58.770 metallic metal, it's not an ion in 07:58.767 --> 08:00.897 solution, it's just a metal. 08:00.900 --> 08:03.130 But, at the surface of the metal an electron could be 08:03.133 --> 08:04.903 transferred to RX. 08:04.900 --> 08:08.800 Now, where does that electron go in the RX? 08:08.800 --> 08:12.270 Ayesha, you got us on to this, tell us again, what orbital 08:12.267 --> 08:13.227 does it go into? 08:13.233 --> 08:14.073 STUDENT: Sigma-star. 08:14.067 --> 08:15.667 PROFESSOR: And what does star mean? 08:15.667 --> 08:16.427 STUDENT: Antibonding. 08:16.433 --> 08:18.173 PROFESSOR: That it's antibonding. 08:18.167 --> 08:19.727 So, what's, going to happen when you put an 08:19.733 --> 08:23.373 electron and get RX-? 08:23.367 --> 08:26.297 It's also a radical, it's got an odd number of electrons. 08:26.300 --> 08:30.700 What's the role of that last electron? 08:30.700 --> 08:31.570 What does the star mean? 08:31.567 --> 08:32.567 STUDENT: Antibonding. 08:32.567 --> 08:33.427 PROFESSOR: Antibonding. 08:33.433 --> 08:34.673 What happens? 08:36.433 --> 08:38.503 We put electrons in the antibonding orbital, 08:38.500 --> 08:39.270 what does it do? 08:39.267 --> 08:39.997 STUDENT: Breaks. 08:40.000 --> 08:43.500 PROFESSOR: Right, breaks the bond. 08:43.500 --> 08:46.170 So, a pair will go there, and now you got 08:46.167 --> 08:48.827 X- and the R radical. 08:48.833 --> 08:51.933 But, the R radical is generated right next to the 08:51.933 --> 08:58.073 metal, so you can get a making of a bond between that radical 08:58.067 --> 08:59.897 and an atom in the metal. 08:59.900 --> 09:01.070 OK. 09:01.067 --> 09:06.167 So, you get an alkyl-metal bond and X-. 09:06.167 --> 09:12.127 This is shown as if the metal is divalent, like zinc, so it 09:12.133 --> 09:15.503 makes a bond to R, and has a positive charge, and then it's 09:15.500 --> 09:17.400 associated with the X-. 09:17.400 --> 09:21.070 If it had been a monovalent metal like lithium, then it 09:21.067 --> 09:25.667 wouldn't have had the charge, it would be RLi, right. 09:25.667 --> 09:27.967 Two lithium atoms would have been involved. 09:27.967 --> 09:32.427 Another one would be Li+ that goes with X-, but at any rate, 09:32.433 --> 09:35.973 this is how you make alkyl-metal bonds 09:35.967 --> 09:37.197 in the first place. 09:39.767 --> 09:44.527 The next three slides suggest a plausible mechanism for this 09:44.533 --> 09:47.673 formation of the cyclopropane, but as we'll see, it's 09:47.667 --> 09:49.367 probably not correct. 09:49.367 --> 09:53.167 But, let's just take this as an opportunity to practice 09:53.167 --> 09:56.667 figuring out how mechanisms might work. 09:56.667 --> 10:04.267 So, we could react zinc with methyl chloride, and we get 10:04.267 --> 10:06.867 this reaction that was shown on the bottom of the previous 10:06.867 --> 10:11.197 slide, a metal-zinc bond and chloride, and I've shown it 10:11.200 --> 10:14.170 covalent between the chloride and the zinc. We 10:14.167 --> 10:17.797 showed +/- last time. 10:17.800 --> 10:21.800 This we're going to use as a model for the actual reaction, 10:21.800 --> 10:26.730 which had CH2I2 as the starting material with zinc. 10:26.733 --> 10:31.333 So, it gave I-Zn-CH2I, so we've simplified it here so we 10:31.333 --> 10:34.973 can draw orbitals that are a little simpler. 10:34.967 --> 10:39.967 That's the LUMO of that model compound and mostly it's a 4s 10:39.967 --> 10:43.367 orbital on the zinc, which is antibonding to the things on 10:43.367 --> 10:48.527 either side, which take away part of it, because you have 10:48.533 --> 10:50.833 antibonding nodes there, of course. 10:50.833 --> 10:53.433 So, that's the LUMO. 10:53.433 --> 10:59.603 The HOMO is mostly a p orbital on the zinc, 10:59.600 --> 11:02.430 actually the LUMO+1. 11:02.433 --> 11:06.503 Now, if you bend the zinc, you'll mix those 11:06.500 --> 11:08.800 two, they'll hybridize. 11:08.800 --> 11:13.570 So, if you bend it, that's the 4p on zinc, if you bend it, as 11:13.567 --> 11:16.497 it's approaching the transition state, where the 11:16.500 --> 11:18.830 zinc is going to be approaching the C-C double 11:18.833 --> 11:22.203 bond, then you hybridize that central one and you've got an 11:22.200 --> 11:23.970 orbital that looks like this. 11:23.967 --> 11:28.197 And, that's an sp hybrid, sp something or other on the 11:28.200 --> 11:36.330 zinc. Notice that that's the LUMO, so what's it well set up 11:36.333 --> 11:40.173 to do with respect to the alkene? 11:40.167 --> 11:42.067 What could it overlap with? 11:42.067 --> 11:42.397 Amy? 11:42.400 --> 11:45.100 STUDENT: The sigma bond HOMO 11:45.100 --> 11:49.470 PROFESSOR: Sigma is down in the middle of the carbons. 11:49.467 --> 11:51.197 STUDENT: Wouldn't the pi be better? 11:51.200 --> 11:53.470 PROFESSOR: The pi is sticking up where 11:53.467 --> 11:55.397 you need it to overlap. 11:55.400 --> 11:58.070 So that can overlap with the HOMO, and you're going to get 11:58.067 --> 12:00.697 a pair of electrons that's bonding between these two 12:00.700 --> 12:04.670 things, between the zinc and the two carbons. 12:04.667 --> 12:07.367 But, this is again one of those cases, so we have an 12:07.367 --> 12:11.097 electrophile on top, a LUMO, attacking an alkene, but we 12:11.100 --> 12:15.200 can also look at the HOMO on top, that's the electrons 12:15.200 --> 12:17.600 shifting into the bonding region. 12:17.600 --> 12:20.870 We can also look at the HOMO on top, and what does that 12:20.867 --> 12:25.097 look well set up to do? 12:25.100 --> 12:29.470 Matt, what do you say, with respect to the alkene? 12:29.467 --> 12:32.067 What orbital of the alkene could that react with? 12:32.067 --> 12:35.297 STUDENT: The double bond, I guess. 12:35.300 --> 12:36.830 PROFESSOR: What about the double bond? 12:36.833 --> 12:38.433 Which specific orbital of the double bond? 12:38.433 --> 12:39.673 STUDENT: The pi-star. 12:39.667 --> 12:41.967 PROFESSOR: pi-star, right, which is the vacant orbital, 12:41.967 --> 12:42.667 which is what you want. 12:42.667 --> 12:47.027 This a HOMO, the LUMO downstairs is what we want 12:47.033 --> 12:49.803 there, and you see those are well set up to react. 12:49.800 --> 12:52.770 We can do electron donation in the other direction, top to 12:52.767 --> 12:57.197 bottom, right, so were taking an electron pair from top to 12:57.200 --> 12:59.570 bottom, also previous slide, bottom to top, so we're 12:59.567 --> 13:02.567 forming two new bonds. 13:02.567 --> 13:07.467 We can draw curved arrows, like this and like that, and 13:07.467 --> 13:11.367 what we've done now is form this product where zinc is 13:11.367 --> 13:13.767 added at one side and methyl at the other. 13:17.833 --> 13:21.533 Now, remember this we just drew so the orbitals would 13:21.533 --> 13:22.603 look simpler. 13:22.600 --> 13:25.870 If we had been using that thing that had two iodines 13:25.867 --> 13:29.097 instead of one chlorine, then the product would have been 13:29.100 --> 13:32.900 this, within the same reaction, but that would have 13:32.900 --> 13:34.100 been the product. 13:34.100 --> 13:35.670 And now, what makes this reactive? 13:38.200 --> 13:42.500 Can you see where there might be a low LUMO in this? 13:42.500 --> 13:43.730 Any ideas? 13:46.833 --> 13:47.273 Cassie? 13:47.267 --> 13:49.567 STUDENT: The sigma-star orbital of the C-l. 13:49.567 --> 13:53.097 PROFESSOR: Sigma star in the carbon-halogen bond. 13:53.100 --> 13:56.430 That would be a low LUMO. 13:56.433 --> 13:59.133 How about the HOMO? 13:59.133 --> 14:02.233 Where would be an unusually high HOMO? 14:02.233 --> 14:08.473 Carbon with a halogen is unusually low, what's the 14:08.467 --> 14:10.767 analog that's unusually high? 14:10.767 --> 14:11.767 Carbon with what? 14:11.767 --> 14:12.497 STUDENT: The zinc atom. 14:12.500 --> 14:16.070 PROFESSOR: With a metal is unusually high. 14:16.067 --> 14:19.267 So, the carbon-zinc bond would be unusually high. 14:19.267 --> 14:25.967 Sigma Zn-C, and the LUMO is sigma-star C-Cl. 14:25.967 --> 14:29.597 I left one of the C's out. 14:29.600 --> 14:30.870 Can you see what can happen? 14:34.467 --> 14:38.467 So, you have a high HOMO attacking a C-X bond, where 14:38.467 --> 14:41.397 have we seen that before? 14:41.400 --> 14:47.200 What reaction has a high HOMO attack sigma-star C-X, where X 14:47.200 --> 14:47.530 is a halogen? 14:47.533 --> 14:49.573 STUDENT: Borohydration. 14:49.567 --> 14:50.897 PROFESSOR: Pardon me? 14:50.900 --> 14:51.900 STUDENT: Borohydration. 14:51.900 --> 14:53.830 PROFESSOR: I can't hear you. 14:53.833 --> 14:55.133 STUDENT: Borohydration. 14:55.133 --> 14:57.803 PROFESSOR: Hydroboration is such a case and I'd have to 14:57.800 --> 14:59.230 think about why this is an example. 14:59.233 --> 15:01.973 I had it even simpler example in mind. 15:01.967 --> 15:02.867 STUDENT: SN2. 15:02.867 --> 15:06.697 PROFESSOR: SN2 right, a backside 15:06.700 --> 15:08.230 attack by the high HOMO. 15:08.233 --> 15:13.773 We can have the HOMO attack the carbon, the iodide is the 15:13.767 --> 15:16.067 leaving group. 15:16.067 --> 15:20.897 That then would form the 3-membered ring. 15:20.900 --> 15:24.670 So that's a very plausible mechanism, it has two steps. 15:24.667 --> 15:31.527 First, you have the addition of zinc halide and the carbon 15:31.533 --> 15:36.503 group, and then in a second step, you do the SN2 type 15:36.500 --> 15:39.430 reaction to form the second bond. 15:39.433 --> 15:42.503 The first reaction formed the bond on the right between the 15:42.500 --> 15:47.630 two CH2's and the second reaction formed this one. 15:47.633 --> 15:50.103 But that probably is not the way it goes. 15:50.100 --> 15:53.200 It's probably not two transition states. 15:53.200 --> 15:55.330 We just guessed that. 15:55.333 --> 15:57.833 There was a quantum mechanical calculation of what the 15:57.833 --> 16:00.473 transition state for this should look like and they 16:00.467 --> 16:02.697 found something different. 16:02.700 --> 16:06.600 Although that mechanism is plausible, it probably occurs 16:06.600 --> 16:09.800 in a single step according to this calculation, with this 16:09.800 --> 16:13.630 bent transition state. 16:13.633 --> 16:16.173 This is the transition state where everything is happening 16:16.167 --> 16:18.767 at once, and let's look at what that is. 16:18.767 --> 16:21.797 First, we could look at how the thing moves through the 16:21.800 --> 16:22.670 transition state. 16:22.667 --> 16:25.367 You see, the carbons going closer, the iodine is going 16:25.367 --> 16:28.267 away from the carbon, and the zinc going away. 16:28.267 --> 16:29.027 Let's see what happens. 16:29.033 --> 16:33.503 Notice incidentally that the CH2 group is like this, and is 16:33.500 --> 16:35.000 rocking in. 16:35.000 --> 16:36.300 Where have you seen that before? 16:39.733 --> 16:46.473 Where the CH2 group approaches sideways and then rocks in? 16:46.467 --> 16:48.397 Seen that before? 16:48.400 --> 16:48.700 Ellen? 16:48.700 --> 16:50.200 STUDENT: The carbene with chlorines. 16:50.200 --> 16:55.500 PROFESSOR: A true carbene, CCl2 did exactly that in order 16:55.500 --> 16:57.630 to get the orbitals to match up. 16:57.633 --> 17:00.733 Let's look at the orbitals in the transition state for this 17:00.733 --> 17:05.003 on the way to making the cyclopropane. 17:05.000 --> 17:09.300 This is at the transition-state geometry. 17:09.300 --> 17:10.370 Here's the LUMO. 17:10.367 --> 17:13.867 What is that LUMO of the zinc reagent? 17:17.200 --> 17:18.600 What would you call that orbital? 17:18.600 --> 17:22.130 STUDENT: Sigma-star. 17:22.133 --> 17:24.373 PROFESSOR: Sigma-star between zinc and the iodine. 17:27.033 --> 17:30.403 That's the LUMO, and you can see it's well set up to mix 17:30.400 --> 17:31.830 with the pi HOMO. 17:31.833 --> 17:35.733 At the same time, this is the HOMO-2. 17:35.733 --> 17:38.573 It's very near the HOMO, so a very high-energy orbital. 17:38.567 --> 17:40.567 What's that well set up to overlap with? 17:40.567 --> 17:44.397 Matt, you're our expert on this? 17:44.400 --> 17:46.500 What about the alkene is well set up there? 17:46.500 --> 17:46.970 STUDENT: The pi-star. 17:46.967 --> 17:48.567 PROFESSOR: pi-star, right. 17:48.567 --> 17:51.567 Blue on the right, red on the left. 17:51.567 --> 17:54.567 We can do both of them at once and make the two new bonds and 17:54.567 --> 17:56.727 break the others. 17:56.733 --> 18:00.333 Here's the next reaction we want to talk about, which is 18:00.333 --> 18:03.333 an analogous reaction in the sense of forming two bonds at 18:03.333 --> 18:07.133 once with a reaction between an alkene and a 18:07.133 --> 18:09.733 percarboxylic acid . 18:09.733 --> 18:12.673 If we didn't have the red oxygen there, if that hydrogen 18:12.667 --> 18:15.927 were directly attached to the oxygen below, that group would 18:15.933 --> 18:17.903 be a carboxylic acid. 18:17.900 --> 18:23.270 This is called the peracid, per- means two oxygens linked 18:23.267 --> 18:26.027 together, which is of course not a very stable bond. 18:26.033 --> 18:27.833 Do you remember why it's not so stable to have two 18:27.833 --> 18:29.073 oxygens in a row? 18:34.100 --> 18:34.370 Natalie? 18:34.367 --> 18:35.867 STUDENT: Repulsion between the electrons. 18:35.867 --> 18:38.327 PROFESSOR: You have two pairs of electrons that are 18:38.333 --> 18:42.673 repelling one another across the bond. 18:42.667 --> 18:47.697 So, meta-chloroperbenzoic acid is a commonly used reagent for 18:47.700 --> 18:51.500 this, and the product, you see, gives the more stable carboxylic 18:51.500 --> 18:54.900 acid, and oxygen attached to the double bond. 18:54.900 --> 18:57.200 Our question is what the mechanism is. 18:57.200 --> 19:00.600 It's also interesting to wonder why you use 19:00.600 --> 19:04.170 meta-chloroperoxybenzoic acid. 19:04.167 --> 19:04.867 Why meta? 19:04.867 --> 19:06.527 Why not para? 19:06.533 --> 19:09.333 It just seems a weird choice. 19:09.333 --> 19:12.703 It's interesting why it's chosen. 19:12.700 --> 19:17.230 It's because it crystallizes very easily, and the crystals 19:17.233 --> 19:20.003 of it are very stable, so it could be stored for a very 19:20.000 --> 19:22.400 long time without any decomposition, even though 19:22.400 --> 19:25.870 essentially it's a rather unstable compound. 19:25.867 --> 19:28.727 It's that practical application that means that 19:28.733 --> 19:32.703 this particular one is the one that's often chosen, although 19:32.700 --> 19:36.800 others could be used as well, other R groups on the peroxy 19:36.800 --> 19:39.700 acid functionality. 19:39.700 --> 19:43.070 OK, so you see in this particular case which I took 19:43.067 --> 19:47.667 as an example from the Jones book, it was done at 25 19:47.667 --> 19:51.297 degrees in benzene for five hours and gave an 81% yield 19:51.300 --> 19:53.900 when R is n-hexyl, so it's a pretty good reaction. 19:56.400 --> 19:59.070 So, to look at what the orbitals are involved, let's 19:59.067 --> 20:06.397 just make that R group instead of meta-chlorobenzene, make it 20:06.400 --> 20:09.800 just the hydrogen, so this is peroxyformic acid, where the 20:09.800 --> 20:12.000 extra oxygen is obviously here. 20:12.000 --> 20:13.430 Had that hydrogen been here, it would 20:13.433 --> 20:16.633 have been formic acid. 20:16.633 --> 20:21.233 Let's just distort that to the geometry it has at the 20:21.233 --> 20:23.473 transition state. 20:23.467 --> 20:27.297 So you see the oxygen-oxygen length increased a little bit, 20:27.300 --> 20:30.900 and the hydrogen bent up a bit. 20:30.900 --> 20:33.970 Now we'll rotate it, so to get the idea of how we're going to 20:33.967 --> 20:38.097 look at it and rotate it back a bit. 20:38.100 --> 20:40.330 Now we're going to look at the orbitals it has, it has a 20:40.333 --> 20:43.833 bunch of occupied orbitals, of course. 20:43.833 --> 20:47.173 And, it has a bunch of unoccupied orbitals. 20:47.167 --> 20:50.927 But, we're particularly interested in its LUMO. 20:50.933 --> 20:53.503 What's the LUMO going to be? 20:53.500 --> 20:54.730 Elisa, what do you think? 21:00.600 --> 21:02.230 There're several possibilities, so come 21:02.233 --> 21:03.473 up with anything. 21:10.867 --> 21:12.367 Anybody else got an idea, Karl? 21:12.367 --> 21:13.527 STUDENT: Sigma-star O-O. 21:13.533 --> 21:17.373 PROFESSOR: Sigma-star O-O. Remember, that's an oxygen, 21:17.367 --> 21:20.397 big nuclear charge. 21:20.400 --> 21:22.830 Can you see any other thing that might be a low LUMO? 21:22.833 --> 21:23.203 Karl? 21:23.200 --> 21:24.870 STUDENT: Pi-star of C-O. 21:24.867 --> 21:27.097 PROFESSOR: Pi-star of C-O is also low. 21:27.100 --> 21:32.370 So in principle, either of those might be the reaction. 21:32.367 --> 21:35.967 So, that's really the problem often in choosing mechanisms, 21:35.967 --> 21:38.097 that there's several possibilities, and you have to 21:38.100 --> 21:40.900 consider them all, and if they're two possibilities, and 21:40.900 --> 21:43.270 then at the next step two more, and two more, it gets to 21:43.267 --> 21:44.527 be a pretty big number. 21:44.533 --> 21:47.003 But at any rate, those are the two that you might consider at 21:47.000 --> 21:52.130 the beginning and once you've tried these several paths, 21:52.133 --> 21:54.733 then you can see which one's going to give you the product 21:54.733 --> 21:57.903 that you know by experiment is actually the product, and it 21:57.900 --> 22:09.300 turns out to be this one, sigma-star O-O. How about the 22:09.300 --> 22:11.000 LUMO of this thing? 22:11.000 --> 22:14.770 Pardon me, that was the LUMO, here's the HOMO, actually it's 22:14.767 --> 22:18.827 not the HOMO, it's the HOMO-3, but do you see 22:18.833 --> 22:21.673 what it's made of? 22:21.667 --> 22:23.167 What's this big thing here? 22:23.167 --> 22:24.897 STUDENT: Unshared pairs. 22:24.900 --> 22:28.330 PROFESSOR: That's the p orbital on oxygen, the 22:28.333 --> 22:31.973 unshared pair, and it's mixed with this up here, which 22:31.967 --> 22:36.397 notice is three p orbitals in a row. 22:36.400 --> 22:42.400 So that's a p orbital on this oxygen and the pi electrons of 22:42.400 --> 22:46.230 the C-O double bond, mixing together in a bonding way here 22:46.233 --> 22:47.833 but antibonding here. 22:47.833 --> 22:52.173 That's why had this been red and that been blue, then this 22:52.167 --> 22:54.767 would have been a lower energy orbital, so this is the 22:54.767 --> 22:57.567 antibonding combination of those two, and it 22:57.567 --> 22:59.897 happens to be HOMO-3. 22:59.900 --> 23:03.770 So that's the HOMO that we're going to be interested in. 23:03.767 --> 23:07.697 So that's mostly, as we said, the pi on that oxygen, the p 23:07.700 --> 23:10.530 orbital, and also pi-allyllic. 23:10.533 --> 23:14.573 Remember allyllic is three p orbitals in a row all pointing 23:14.567 --> 23:17.127 in the same direction so they overlap side to side. 23:19.867 --> 23:22.067 And there we've turned it a little further just so you can 23:22.067 --> 23:24.667 see that it's those p orbitals. 23:24.667 --> 23:27.027 Now we're going to look at it as it interacts with the 23:27.033 --> 23:29.973 carbon-carbon double bond. 23:29.967 --> 23:33.067 The first interaction is going to be that LUMO of the 23:33.067 --> 23:35.597 oxygen-oxygen bond, sigma-star, that's the 23:35.600 --> 23:40.870 electrophile, that's the LUMO, and the high occupied orbital is 23:40.867 --> 23:47.167 going to be our old favorite, pi of the double bond. 23:47.167 --> 23:48.067 We'll do this. 23:48.067 --> 23:50.697 What does that reaction remind you of a little bit, when 23:50.700 --> 23:53.430 something comes in from one side, and the group leaves with 23:53.433 --> 23:56.703 its electrons from the other side? 23:56.700 --> 24:00.770 SN2 of course, so it's the same kind of reaction. 24:00.767 --> 24:05.767 So that's an SN2 attacking oxygen, not carbon of course. 24:05.767 --> 24:09.367 So, that's going to form a new bond, and the leaving group, 24:09.367 --> 24:11.197 notice, is a fairly good anion, 24:11.200 --> 24:15.470 carboxylate, better than RO-. 24:18.267 --> 24:19.867 Now, what makes this reactive? 24:19.867 --> 24:22.667 What could happen next? 24:22.667 --> 24:22.897 Elisa? 24:22.900 --> 24:25.270 STUDENT: You have a positive charge on the carbon. 24:25.267 --> 24:27.597 PROFESSOR: We've got a positive charge on carbon, so 24:27.600 --> 24:29.930 that's going to be a very low energy orbital there. 24:33.533 --> 24:38.503 Where could be a HOMO that would react with that? 24:38.500 --> 24:39.800 A high occupied orbital. 24:42.667 --> 24:43.067 Liang? 24:43.067 --> 24:43.997 STUDENT: The lone pair on oxygen. 24:44.000 --> 24:46.200 PROFESSOR: OK, it could be. 24:46.200 --> 24:49.200 That wasn't what I expected you to say, that's going to be 24:49.200 --> 24:51.000 what it is. 24:51.000 --> 24:52.530 What other possibility? 24:52.533 --> 24:53.233 Liang? 24:53.233 --> 24:57.003 [LAUGHTER] 24:57.000 --> 25:00.300 Liang, what other possibility is there when you look at this 25:00.300 --> 25:01.570 picture for a high HOMO? 25:06.167 --> 25:12.167 STUDENT: The negative charge on the-- 25:12.167 --> 25:14.227 PROFESSOR: Right, we got a negative charge up here. 25:14.233 --> 25:17.503 This oxygen looks to me like it has a higher HOMO 25:17.500 --> 25:19.230 than this one does. 25:19.233 --> 25:22.073 What advantages does yours have over the 25:22.067 --> 25:23.027 one that's up there? 25:23.033 --> 25:24.203 STUDENT: It's closer. 25:24.200 --> 25:25.200 PROFESSOR: Pardon me? 25:25.200 --> 25:25.970 STUDENT: It's closer. 25:25.967 --> 25:28.997 PROFESSOR: It's closer, right. 25:29.000 --> 25:32.700 The electrophile is going to be what Elisa said, the p 25:32.700 --> 25:35.170 orbital on the carbon plus. 25:35.167 --> 25:38.797 But, the p orbital on the oxygen is going to be the 25:38.800 --> 25:43.170 nucleophile, and it has the advantage of being nearby. 25:43.167 --> 25:49.127 So that means we can do this and make a second bond, and of 25:49.133 --> 25:50.933 course the plus charge will move when 25:50.933 --> 25:53.573 we share the electrons. 25:53.567 --> 25:55.597 Now, what do we have for a LUMO here? 25:58.933 --> 26:00.503 If we're going to do another reaction? 26:06.133 --> 26:08.233 It's something to do with a positive charge. 26:08.233 --> 26:11.733 What particular orbital would you point to, if we had to 26:11.733 --> 26:14.473 choose a particular orbital? 26:14.467 --> 26:16.967 The charge is not an orbital. 26:16.967 --> 26:20.067 The charge makes an orbital low, makes the electrons in an 26:20.067 --> 26:22.227 orbital, low in energy nearby. 26:22.233 --> 26:24.873 But, what orbital will we look at? 26:24.867 --> 26:25.767 Jack, you got an idea? 26:25.767 --> 26:26.627 STUDENT: Pi. 26:26.633 --> 26:27.933 PROFESSOR: Pardon me. 26:27.933 --> 26:28.833 STUDENT: Pi. 26:28.833 --> 26:29.473 PROFESSOR: I couldn't hear. 26:29.467 --> 26:30.327 STUDENT: Pi. 26:30.333 --> 26:31.503 PROFESSOR: Which pi? 26:31.500 --> 26:33.600 STUDENT: The one with oxygen. 26:33.600 --> 26:35.730 PROFESSOR: A p orbital on oxygen? 26:39.000 --> 26:42.570 The p orbitals on oxygen are all filled with electrons. 26:42.567 --> 26:45.167 We're looking for a vacant orbital, right? 26:45.167 --> 26:48.167 It's true that the unshared pair on oxygen is lower in 26:48.167 --> 26:50.827 energy than it would normally be, but that 26:50.833 --> 26:53.833 doesn't make it reactive. 26:53.833 --> 26:56.903 For a pair of electrons to be reactive they have to be high 26:56.900 --> 26:59.000 in energy, not low. 26:59.000 --> 27:02.030 We want some vacant orbital that will be 27:02.033 --> 27:04.333 unusually low in energy. 27:04.333 --> 27:04.673 Chris? 27:04.667 --> 27:06.567 STUDENT: d orbital? 27:06.567 --> 27:08.097 PROFESSOR: The d orbital? 27:08.100 --> 27:10.670 No, you know, if you get to sulfur or something, if you 27:10.667 --> 27:12.967 get down in the next row of the periodic table, then there 27:12.967 --> 27:17.227 are d orbitals that are vacant in the valence shell, but on 27:17.233 --> 27:20.033 oxygen d is way up in the next shell. 27:20.033 --> 27:21.033 STUDENT: Sigma-star. 27:21.033 --> 27:22.373 PROFESSOR: Sigma-star. 27:22.367 --> 27:23.167 STUDENT: of C-O? 27:23.167 --> 27:26.997 PROFESSOR: It could be sigma star C-O. Any other 27:27.000 --> 27:28.170 possibilities? 27:28.167 --> 27:31.367 It could be sigma-star C-O. Any other possibilities? 27:31.367 --> 27:33.167 STUDENT: Sigma-star O-H. 27:33.167 --> 27:36.927 PROFESSOR: Sigma-star O-H. Right. 27:36.933 --> 27:39.473 That's the kind of thing you're thinking of, because 27:39.467 --> 27:45.067 when you have an O+ that's protonated, three bonds, one 27:45.067 --> 27:48.967 of them to a proton, what do you think of happening? 27:48.967 --> 27:53.597 Losing a proton, right, and that's that sigma-star O-H. So 27:53.600 --> 27:57.200 that's going to be our electrophile, that's where the 27:57.200 --> 27:59.670 electrons are going to go, into sigma-star O-H 27:59.667 --> 28:00.897 and break that bond. 28:00.900 --> 28:02.030 Where they going to come from? 28:02.033 --> 28:03.403 Where's the high HOMO? 28:03.400 --> 28:05.170 Liang, let's go back to you now. 28:05.167 --> 28:06.167 STUDENT: Negative charge. 28:06.167 --> 28:08.267 PROFESSOR: Now you've got the negative charge here. 28:08.267 --> 28:09.927 But there's something interesting about this 28:09.933 --> 28:11.133 negative charge. 28:11.133 --> 28:13.573 The reason that was a good place to put a negative 28:13.567 --> 28:16.767 charge, that carboxylate was a good leaving group, was that 28:16.767 --> 28:21.227 there was a carbonyl group, a C-O double bond next door. 28:21.233 --> 28:23.073 We can denote that-- 28:23.067 --> 28:26.427 so we're going to have an SN2 at H. We're going to attack, 28:26.433 --> 28:31.533 and notice where we're going to attack from, backside. 28:31.533 --> 28:33.873 These attacks are always backside to break a 28:33.867 --> 28:36.027 sigma-star. 28:36.033 --> 28:41.373 Now, the trouble with this O- is that it's not backside, 28:41.367 --> 28:44.297 it's out in the front. 28:44.300 --> 28:46.670 Can you see how we could get it into the back? 28:49.500 --> 28:53.100 How could we get this charge back near here? 28:55.967 --> 28:59.127 One way that Karl suggests is move the anion, it's not 28:59.133 --> 29:01.003 bonded after all. 29:01.000 --> 29:04.400 But, there's a cleverer way to do it. 29:04.400 --> 29:05.770 Not that you're not clever, Karl. 29:09.500 --> 29:10.770 Watch this. 29:13.367 --> 29:14.367 Does that suggest anything? 29:14.367 --> 29:17.097 That's why carboxylate is a good leaving group, because 29:17.100 --> 29:18.800 it's resonance-stabilized. 29:18.800 --> 29:20.070 But, what does that suggest? 29:22.300 --> 29:23.530 Sebastian? 29:25.600 --> 29:30.600 You don't need to use this anion, you can use this anion, 29:30.600 --> 29:33.830 because the charge is both places here. 29:33.833 --> 29:38.733 So we can draw that, put the charge over there, and a 29:38.733 --> 29:41.333 double bond here in front. 29:41.333 --> 29:46.073 So now we've got it where it needs to be. Now we can do the 29:46.067 --> 29:48.997 backside attack, move the proton over. 29:51.600 --> 29:55.070 We have those products, the carboxylic acid without it's 29:55.067 --> 29:59.027 oxygen, that extra oxygen that the peracid had, and oxygen 29:59.033 --> 30:01.973 added to the carbon-carbon double bond to give a 30:01.967 --> 30:06.427 3-membered ring, an oxirane as it's called, or an epoxide. 30:09.167 --> 30:10.767 The interesting thing about this-- 30:13.500 --> 30:15.830 Karl had the great idea, let's just move it to 30:15.833 --> 30:17.533 where it needs to be. 30:17.533 --> 30:21.033 But there's a reason I didn't want to move things. 30:21.033 --> 30:26.903 The reason is, that in fact, all those steps are not steps. 30:26.900 --> 30:31.000 They all happen at the same time. 30:31.000 --> 30:34.670 So in fact when you start with that material, and bring it up 30:34.667 --> 30:37.567 to the carbon-carbon double bond, all those 30:37.567 --> 30:38.827 things happen at once. 30:41.433 --> 30:44.473 It made sense looking at them one at a time, but in fact 30:44.467 --> 30:47.727 they can all happen at the same time. 30:47.733 --> 30:50.073 So you have minimal atomic displacement if you go 30:50.067 --> 30:55.767 directly from this to transfer the oxygen atom and get that. 30:55.767 --> 30:58.327 But, they don't happen strictly in parallel, just 30:58.333 --> 31:01.273 because they're all happening at the same time, doesn't mean 31:01.267 --> 31:04.097 that they're all half way done at the same time. 31:04.100 --> 31:06.570 Some are a little leading, some are a little trailing, 31:06.567 --> 31:08.497 but they're all happening together with 31:08.500 --> 31:10.230 minimal atomic motion. 31:10.233 --> 31:11.673 How do I know that? 31:11.667 --> 31:15.827 Because of this paper that was published in JACS in 1991. 31:15.833 --> 31:18.233 Now that's 20 years ago, and you can do much better 31:18.233 --> 31:20.003 calculations I'm sure now. 31:20.000 --> 31:22.570 But, this is when it was done and published and it's 31:22.567 --> 31:23.467 believable. 31:23.467 --> 31:26.397 This is what they calculated for the geometry at the 31:26.400 --> 31:32.100 transition state, and they give in every case what the 31:32.100 --> 31:36.370 length of that bond, and what the bond angles are. 31:36.367 --> 31:39.397 Notice that that O-O is strongly stretched at the 31:39.400 --> 31:42.600 transition state, so it's really broken a lot, putting 31:42.600 --> 31:44.670 the electrons in the anti-bond. 31:44.667 --> 31:50.027 It's started to break, it's 1.87, where normally it was 31:50.033 --> 31:53.203 1.5, roughly. 31:53.200 --> 31:56.070 Notice that the O-H bond, remember that H is going to 31:56.067 --> 32:00.267 transfer from O1 to O3, at the transition state it is hardly 32:00.267 --> 32:01.067 stretched at all. 32:01.067 --> 32:05.197 It started at about one angstrom and it's 1.01 here at 32:05.200 --> 32:07.700 the transition state. 32:07.700 --> 32:11.170 It actually is going to do most of its motion after the 32:11.167 --> 32:13.197 transition state. 32:13.200 --> 32:17.830 I put KH/KD is about one, that is there's not a kinetic 32:17.833 --> 32:19.603 isotope effect on this. 32:19.600 --> 32:22.270 Does that surprise you that there's not a 32:22.267 --> 32:23.497 kinetic isotope effect? 32:25.667 --> 32:26.897 That deuterium and hydrogen are 32:26.900 --> 32:28.670 transferred at the same rate? 32:31.267 --> 32:35.067 What does it tell you, when there's a hydrogen isotope 32:35.067 --> 32:38.167 effect, a hydrogen-deuterium isotope effect? 32:38.167 --> 32:40.597 What does that tell you about the mechanism, about the 32:40.600 --> 32:41.500 transition state? 32:41.500 --> 32:44.500 STUDENT: That it's an intermediate. 32:44.500 --> 32:46.530 PROFESSOR: No, it doesn't tell you, it's an intermediate. 32:49.133 --> 32:51.433 STUDENT: That the deprotonation is 32:51.433 --> 32:52.833 the limiting step. 32:52.833 --> 32:55.633 PROFESSOR: The rate limiting step, the hydrogen is being 32:55.633 --> 32:59.203 transferred, not before, not after, but at the rate 32:59.200 --> 33:00.600 limiting step. 33:00.600 --> 33:03.570 But, in this case, the bond isn't much stretched at the 33:03.567 --> 33:07.967 transition state, so there's not an isotope effect, because 33:07.967 --> 33:12.797 most of the transfer of the hydrogen is happening later. 33:12.800 --> 33:16.130 This shows the motion, successive motions. 33:16.133 --> 33:21.603 Here's the transition state, then P1, P2 are subsequent 33:21.600 --> 33:24.500 stages on the reaction pathway. 33:24.500 --> 33:28.030 If you look at the motion of each atom, you see the 33:28.033 --> 33:30.833 hydrogen does most of its motion from this oxygen to 33:30.833 --> 33:35.473 this oxygen after the transition state. 33:35.467 --> 33:39.427 So, just because all these things are coordinated, you 33:39.433 --> 33:41.503 don't have distinct intermediates, you have only 33:41.500 --> 33:45.400 one transition state, but they don't all have to be 50% of 33:45.400 --> 33:47.270 the way from starting material to product at 33:47.267 --> 33:49.827 exactly the same instant. 33:49.833 --> 33:52.303 You can see how the others are moving as well. 33:52.300 --> 33:57.830 So, notice that after the transition state, the 33:57.833 --> 34:00.833 hydrogens are moving down a little bit, the carbons are 34:00.833 --> 34:03.533 moving up, the oxygen is moving in here to make the new 34:03.533 --> 34:06.633 bond, and so on, and the hydrogen is moving away. 34:06.633 --> 34:11.473 This thing, the carboxylate at the top is rocking away, 34:11.467 --> 34:14.027 breaking the oxygen-oxygen bond here, and 34:14.033 --> 34:17.933 forming the OH bond here. 34:17.933 --> 34:20.573 There's only one transition state, this is said to be 34:20.567 --> 34:23.827 concerted in the sense things are happening at the same 34:23.833 --> 34:26.903 time, not several distinct intermediates. 34:26.900 --> 34:28.730 But it's not synchronous, it's not all 34:28.733 --> 34:30.433 happening exactly in parallel. 34:33.667 --> 34:37.097 The name of this transition state, they called it spiro 34:37.100 --> 34:38.600 transition state. 34:38.600 --> 34:43.930 Spiro means two perpendicular rings sharing a common atom. 34:43.933 --> 34:47.733 Here it's O1, here's this five-membered ring here, and a 34:47.733 --> 34:50.733 three-membered ring here, but they're perpendicular to one 34:50.733 --> 34:52.403 another, they share an atom. 34:52.400 --> 34:56.370 That's what spiro means, to have two rings that are spiro, 34:56.367 --> 34:59.967 they share an atom and are perpendicular to one another. 34:59.967 --> 35:03.667 But, in fact, a very similar mechanism, in fact arguably 35:03.667 --> 35:06.827 the same mechanism, was proposed by Professor 35:06.833 --> 35:11.073 Bartlett, your grandfather, in 1950. 35:11.067 --> 35:14.767 This was before people thought so much about spiro and about 35:14.767 --> 35:17.397 the arrangement in space of orbitals as they do now. 35:17.400 --> 35:19.500 In fact, they didn't think about orbitals at 35:19.500 --> 35:21.630 all really in 1950. 35:21.633 --> 35:26.573 So, in a paper in 1950, he drew this structure, which 35:26.567 --> 35:30.067 shows the peroxycarboxylic acid twisted around, so the 35:30.067 --> 35:34.067 hydrogen can make it from here to here, and the oxygen then 35:34.067 --> 35:35.467 be transferred to that. 35:35.467 --> 35:39.297 So this picture is taken from that publication in 1950. 35:39.300 --> 35:42.630 You'll notice that the arrows were not at all carefully 35:42.633 --> 35:46.273 drawn, and it's not clear what they mean. 35:46.267 --> 35:50.597 This hydrogen in fact started attached to this oxygen, and 35:50.600 --> 35:54.030 is now moved over to this oxygen in the product, so I 35:54.033 --> 35:56.303 have no idea really what that arrow meant. 35:59.733 --> 36:02.373 But, that was old days, right, before people talked about 36:02.367 --> 36:05.467 orbitals and so on, 60 years ago. 36:05.467 --> 36:08.827 The problem is, how about now, how carefully do people draw 36:08.833 --> 36:10.273 such things now? 36:10.267 --> 36:13.367 Well, we could look at a modern textbook that has a 36:13.367 --> 36:16.227 drawing of this particular reaction, and 36:16.233 --> 36:17.973 draws it in that way. 36:17.967 --> 36:21.367 What I'd like you to think of for a problem is, compare the 36:21.367 --> 36:24.667 arrows in this textbook illustration, with the ones 36:24.667 --> 36:27.197 that we developed in the previous frame to show where 36:27.200 --> 36:29.470 HOMOs and LUMOs were interacting, and how electron 36:29.467 --> 36:33.227 pairs were shifting, and see if you can draw your own 36:33.233 --> 36:36.773 diagram that's more accurate than this textbook one is. 36:41.667 --> 36:45.627 Stereospecificity of this epoxidation, if the oxygen is 36:45.633 --> 36:49.273 really being transferred this way, all at once, the two new 36:49.267 --> 36:53.867 bonds have to be on the same face of the double bond. 36:53.867 --> 36:59.097 So, if you started with trans-2-butene and used this 36:59.100 --> 37:03.430 meta-chloroperbenzoic acid, and this is a specific example 37:03.433 --> 37:06.073 done in this solvent, dioxane, at 0 37:06.067 --> 37:08.027 degrees for 10 hours. 37:08.033 --> 37:12.373 Notice that these two methyl groups are on opposite sides 37:12.367 --> 37:15.867 of the 3-membered ring, just as they were on opposite sides 37:15.867 --> 37:18.967 of the pi bond here. 37:18.967 --> 37:23.967 This happens with 52% to 60% percent yield, but more 37:23.967 --> 37:31.467 significant, is that it's greater than 99.5% trans. 37:31.467 --> 37:34.727 This is an actual 52% to 60% yield, that's what they 37:34.733 --> 37:38.403 actually got of pure stuff and put it in the bottle. 37:38.400 --> 37:40.970 And you know, that if you have to distill stuff at the end 37:40.967 --> 37:47.097 and so on, you don't always get 100%. 37:47.100 --> 37:51.330 If all they had said, was that a 60% yield, you'd worry, what's 37:51.333 --> 37:53.173 that other 40%? 37:53.167 --> 37:56.497 Could it be the cis isomer? 37:56.500 --> 37:59.300 In fact, that's not what it was, because they tested and 37:59.300 --> 38:04.300 found that there was no cis there, it was more than 99.5, 38:04.300 --> 38:08.270 the limits of their detection was trans, so it's a concerted 38:08.267 --> 38:11.767 syn addition, both new bonds from the 38:11.767 --> 38:15.097 same face of the alkene. 38:15.100 --> 38:18.130 And, you'd worry about this also, that this is the more 38:18.133 --> 38:20.933 stable isomer, where the methyls aren't running into 38:20.933 --> 38:21.773 one another. 38:21.767 --> 38:24.967 Maybe it wasn't specific, but you just got the one that was 38:24.967 --> 38:26.567 most stable. 38:26.567 --> 38:29.727 So, of course what they did is do the cis one as well, and 38:29.733 --> 38:34.873 that's also greater than 99.5%, cis now, not trans. 38:34.867 --> 38:37.167 It's clear that the reaction is stereospecific. 38:40.767 --> 38:45.167 They did that in order to prepare those epoxides for 38:45.167 --> 38:46.227 another purpose. 38:46.233 --> 38:49.233 It'd been prepared before, in 1936, by 38:49.233 --> 38:52.603 an alternative mechanism. 38:52.600 --> 38:55.230 It was two steps to do it, so it was a 38:55.233 --> 38:57.103 harder way to make it. 38:57.100 --> 38:59.030 They started with the reagent HOCl, hypochlorous acid. 39:02.000 --> 39:04.370 How do you think HOCl will react? 39:08.600 --> 39:09.830 Any ideas? 39:12.667 --> 39:15.267 What other reagent that we've talked about reacting does 39:15.267 --> 39:17.427 that remind you of? 39:17.433 --> 39:21.773 This is a chlorine, with an electronegative bond to it, 39:21.767 --> 39:23.067 bond to oxygen. 39:23.067 --> 39:27.397 What's the LUMO of that, do you think? 39:36.667 --> 39:37.097 Cassie? 39:37.100 --> 39:38.070 STUDENT: The O-Cl sigma-star. 39:38.067 --> 39:43.267 PROFESSOR: Right, O-Cl sigma-star, the same as Cl-Cl 39:43.267 --> 39:44.967 sigma-star. 39:44.967 --> 39:47.727 What kind of thing happens with Cl-Cl sigma-star 39:47.733 --> 39:51.203 remember, if you react it with an alkene? 39:54.333 --> 39:58.303 It forms a halonium ion, like that. 39:58.300 --> 40:01.230 The only difference is that in that case, it was Cl- that's 40:01.233 --> 40:06.033 leaving, in this case it's OH- that's leaving. 40:06.033 --> 40:09.273 But, that's drawn in brackets because it's just an 40:09.267 --> 40:11.667 intermediate, it's not something that you isolate, 40:11.667 --> 40:14.297 it's very reactive. 40:14.300 --> 40:17.630 Remember you made hydroxide, so what's going to be the next 40:17.633 --> 40:18.803 stage of the reaction. 40:18.800 --> 40:22.030 How will this react with hydroxide? 40:22.033 --> 40:24.033 How does the one that had a chlorine on 40:24.033 --> 40:25.333 it react with chlorine? 40:29.167 --> 40:32.067 It's an SN2 kind of reaction. 40:32.067 --> 40:34.997 In fact, you have water here that can also do it. 40:35.000 --> 40:39.970 It gives a 55% yield after distillation of this stuff, 40:39.967 --> 40:42.367 where you notice what happened was the oxygen attacked 40:42.367 --> 40:45.867 backside, opened this ring. 40:45.867 --> 40:50.327 So this methyl group is back, and this methyl group is back, 40:50.333 --> 40:53.073 since we started with cis. 40:53.067 --> 40:55.627 We've got correlated configurations 40:55.633 --> 40:57.033 at these two carbons. 40:57.033 --> 40:59.773 Notice it would have been just as easy for the oxygen to 40:59.767 --> 41:02.997 attack this carbon, it attacked this one, it could 41:03.000 --> 41:05.370 have attacked this one. 41:05.367 --> 41:08.827 So it came this way, it could have come this way. 41:08.833 --> 41:11.373 What's the relationship between the two products you 41:11.367 --> 41:12.897 would get if you did those two reactions? 41:20.867 --> 41:21.127 Ellen? 41:21.133 --> 41:21.833 STUDENT: Enantiomers. 41:21.833 --> 41:23.903 PROFESSOR: They're enantiomers. 41:23.900 --> 41:27.030 So you get not just this compound, but also it's 41:27.033 --> 41:29.403 enantiomer. 41:29.400 --> 41:32.770 But, you don't get ones where this methyl would be in front 41:32.767 --> 41:35.897 of the hydrogen in back, as shown there. 41:35.900 --> 41:39.330 There are four diastereomers, you only get two of them, you 41:39.333 --> 41:42.373 get the two enantiomers. 41:42.367 --> 41:45.227 So that's the first reaction, they did it, they got a 55% 41:45.233 --> 41:47.003 yield after distillation. 41:47.000 --> 41:52.100 Then they reacted it with KOH, notice it's 20 M KOH, pretty 41:52.100 --> 41:56.070 strong solution at 90 degrees, that's vigorous conditions, in 41:56.067 --> 41:57.867 water for two hours. 41:57.867 --> 42:01.697 How do you think OH- will react with this stuff? 42:01.700 --> 42:05.270 I want several possibilities. 42:05.267 --> 42:10.027 What could OH- attack in this molecule? 42:10.033 --> 42:10.503 Chris? 42:10.500 --> 42:11.500 STUDENT: Deprotonate the hydrogen. 42:11.500 --> 42:13.670 PROFESSOR: Deprotonate the hydrogen. 42:13.667 --> 42:15.327 What would have been another possibility? 42:15.333 --> 42:16.633 STUDENT: Attack the chlorine. 42:16.633 --> 42:18.803 PROFESSOR: It could've attacked-- 42:18.800 --> 42:21.330 done an SN2 here on the other one, but it's 42:21.333 --> 42:23.833 a little bit hindered. 42:23.833 --> 42:28.073 Generally proton transfers are pretty fast, so you were right 42:28.067 --> 42:29.197 the first time. 42:29.200 --> 42:33.170 The KOH takes off that and generates that anion. 42:33.167 --> 42:36.167 Now again, I've drawn that in brackets because it's just an 42:36.167 --> 42:37.397 intermediate. 42:37.400 --> 42:38.630 What does it do? 42:41.033 --> 42:45.073 What does this O- do? 42:45.067 --> 42:46.327 Chris, you just told me. 42:49.700 --> 42:50.170 What can it attack? 42:50.167 --> 42:54.567 STUDENT: The lone pair on the oxygen. 42:54.567 --> 42:58.967 PROFESSOR: It is the lone pair on the oxygen, that's the high 42:58.967 --> 43:00.667 HOMO, what's the low LUMO? 43:00.667 --> 43:04.927 STUDENT: The sigma-star carbon... 43:04.933 --> 43:07.773 PROFESSOR: Yeah, sigma-star carbon-chlorine. 43:07.767 --> 43:09.767 What would you call that kind of reaction, ever see a 43:09.767 --> 43:13.267 reaction like that before, where O- attacks carbon and 43:13.267 --> 43:14.527 chloride leaves? 43:17.900 --> 43:19.670 Noelle, did you ever see a reaction like that? 43:19.667 --> 43:21.697 STUDENT: SN2. 43:21.700 --> 43:22.400 PROFESSOR: Can't hear. 43:22.400 --> 43:23.400 STUDENT: SN2. 43:23.400 --> 43:25.700 PROFESSOR: It's SN2, right, and it's helped out because 43:25.700 --> 43:27.870 this is held very close to where it needs to 43:27.867 --> 43:29.567 be to do the reaction. 43:29.567 --> 43:32.127 OK, so we do that. 43:32.133 --> 43:34.733 Now, we form the epoxide. 43:37.933 --> 43:40.703 Notice the stereochemistry of this is interesting. 43:40.700 --> 43:45.000 The two carbons are on the same side of the ring, the 43:45.000 --> 43:49.000 same way they were on the same side of the pi bond here. 43:49.000 --> 43:52.130 But, the stereochemistry happened in sort of an 43:52.133 --> 43:53.973 interesting way. 43:53.967 --> 43:56.327 This is a 90% yield that they got in this 43:56.333 --> 43:57.803 in the second step. 43:57.800 --> 44:00.770 But, since they had to do two reactions from the starting 44:00.767 --> 44:04.897 material, the overall yield was only 45% from the original 44:04.900 --> 44:06.400 starting material. 44:06.400 --> 44:08.870 Do you remember what it was when they used 44:08.867 --> 44:13.667 meta-chloroperoxybenzoic acid in the previous example to 44:13.667 --> 44:16.667 make the same substance from the same starting material? 44:16.667 --> 44:17.827 You remember what the yield was? 44:17.833 --> 44:18.773 STUDENT: 60% 44:18.767 --> 44:20.997 PROFESSOR: Yeah, it was 60%. 44:21.000 --> 44:23.970 So nearly half again as much, at least a third again as 44:23.967 --> 44:26.697 much, and in just one reaction, you didn't have to 44:26.700 --> 44:28.700 do this distillation and so on, so it was much more 44:28.700 --> 44:29.930 convenient. 44:29.933 --> 44:33.573 That one, the oxygen just went straight on, and 44:33.567 --> 44:34.927 it was a syn addition. 44:34.933 --> 44:37.873 This one happens in an interesting way. 44:37.867 --> 44:41.667 First, it's a syn addition of the Cl+, both from the same 44:41.667 --> 44:45.567 side, but then there's this SN2 kind of reaction, and it's 44:45.567 --> 44:48.267 an inversion at this carbon. 44:48.267 --> 44:53.997 And, then here, there's an inversion at that carbon. 44:54.000 --> 44:57.800 So overall, it's still a syn addition, but by two 44:57.800 --> 45:00.470 inversions. 45:00.467 --> 45:02.397 So, that's interesting. 45:02.400 --> 45:05.900 This is somewhat reminiscent of what we talked about last 45:05.900 --> 45:08.700 semester, which is the Sharpless asymmetric 45:08.700 --> 45:10.400 epoxidation. 45:10.400 --> 45:12.370 I'll just run through this quickly, we've done it several 45:12.367 --> 45:13.297 times before. 45:13.300 --> 45:18.270 So, you lose the RO-, then a peroxy group comes up to the 45:18.267 --> 45:23.427 titanium. We get that intermediate and react it 45:23.433 --> 45:25.473 with allyl alcohol. 45:25.467 --> 45:31.897 The OH of the allyl alcohol replaces the RO, it replaces 45:31.900 --> 45:32.930 there, to get this. 45:32.933 --> 45:37.203 And, now this double bond is being held near this oxygen. 45:37.200 --> 45:40.030 The LUMO is the sigma-star up there, the same thing we've 45:40.033 --> 45:44.673 been talking about, and the HOMO is pi. 45:44.667 --> 45:46.897 So, we've made a bond. 45:46.900 --> 45:50.900 In fact, this pair of electrons probably then makes 45:50.900 --> 45:54.100 a bond between oxygen and this titanium, rather than the RO 45:54.100 --> 45:55.630 going away. 45:55.633 --> 45:58.933 But, at the same time, there's also the p on the oxygen 45:58.933 --> 46:03.403 attacking pi-star of C-C. This is exactly the same thing we 46:03.400 --> 46:07.830 just saw a few slides ago with peroxy benzoic acid. 46:07.833 --> 46:12.773 We make two bonds, and put the oxygen on from the same face. 46:12.767 --> 46:16.797 This particular arrangement makes the R configuration at 46:16.800 --> 46:19.730 this tetrahedral carbon. 46:19.733 --> 46:24.103 If we wanted to get the other one, we'd have to rotate this 46:24.100 --> 46:27.030 bond to be in front, and this to be in back, so that we 46:27.033 --> 46:31.573 could attack the other face, rotate it back like that. 46:31.567 --> 46:34.767 You'll notice that if you do that, those two groups in 46:34.767 --> 46:38.727 front are big, and they would run into one another. 46:38.733 --> 46:41.203 So you don't do that, you do the other one, and it gives us 46:41.200 --> 46:44.230 a specific enantiomer of the epoxide. 46:44.233 --> 46:46.373 But the relevance at this stage-- 46:46.367 --> 46:49.297 that we talked about last semester, the relevance at 46:49.300 --> 46:52.730 this stage is that it's essentially the same mechanism 46:52.733 --> 46:55.403 that's involved in the peroxybenzoic acid of the 46:55.400 --> 46:57.400 electrons forming the two new bonds. 47:00.467 --> 47:04.097 That was a chiral oxidizing agent. 47:04.100 --> 47:06.270 Now, this is a big time-- 47:06.267 --> 47:09.927 making epoxides from alkenes is really a big time 47:09.933 --> 47:12.073 operation, as is shown here. 47:12.067 --> 47:15.727 This is done with silver catalysis at 15 atmospheres of 47:15.733 --> 47:19.333 pressure and 250 degrees Celsius. 47:19.333 --> 47:22.933 Notice that the source of oxygen is O2 in this case, 47:22.933 --> 47:25.603 that's a really cheap source of oxygen. 47:25.600 --> 47:27.170 In fact, they do use O2. 47:27.167 --> 47:30.997 There are other people who do the same kind of thing who use 47:31.000 --> 47:34.900 air, but it turns out to be worthwhile to use O2 rather 47:34.900 --> 47:37.670 than air, because you get a higher yield. 47:37.667 --> 47:41.697 So what you get is an oxygen that's transferred like that, 47:41.700 --> 47:44.730 that's called ethylene oxide. 47:44.733 --> 47:51.033 That process generates 20 million tons a year, worth 20 47:51.033 --> 47:54.703 billion dollars, of making ethylene oxide. 47:54.700 --> 47:57.330 Just to give you an idea, here's an aerial view of New 47:57.333 --> 47:59.973 Haven, and down here is where most of you 47:59.967 --> 48:02.697 live on the old campus. 48:02.700 --> 48:05.770 If you had a bucket that would hold that much ethylene oxide 48:05.767 --> 48:08.797 as a liquid, it's a gas, but if you condensed it, it would 48:08.800 --> 48:09.370 be a liquid. 48:09.367 --> 48:11.497 That's how big the bucket would be. 48:11.500 --> 48:13.870 [LAUGHTER] 48:13.867 --> 48:17.797 I think it's 15 times as high as Harkness Tower and covering 48:17.800 --> 48:20.100 the entire old campus. 48:20.100 --> 48:21.830 So, that's a lot of material. 48:21.833 --> 48:29.833 Now that reaction gives 84% yield, the rest oxidizes, the 48:29.833 --> 48:34.333 rest of the original ethylene oxidizes to CO2 and H2O. 48:34.333 --> 48:36.433 Suppose you could adjust the conditions to 48:36.433 --> 48:38.603 make the yield higher. 48:38.600 --> 48:42.870 Suppose instead of 84%, you could increase it by 5%. 48:42.867 --> 48:46.167 If you could raise the yield by 5%, that would be worth 48:46.167 --> 48:49.267 more than a billion dollars a year. 48:49.267 --> 48:51.927 So, here's a way for you to make your fortune. 48:51.933 --> 48:55.273 Although, I will caution you that people have worked on 48:55.267 --> 48:58.997 this a lot to try to get every last percentage out of it. 49:03.100 --> 49:07.530 In fact, why make 20 million tons of ethylene oxide? 49:07.533 --> 49:12.773 Only 0.05% of it is used as ethylene oxide. 49:12.767 --> 49:18.127 It's a disinfectant that's used in some applications, 49:18.133 --> 49:20.103 it's a gas, and you can put it in to 49:20.100 --> 49:22.170 kill microbes or something. 49:22.167 --> 49:24.467 But, very, very little of it is used for. 49:24.467 --> 49:26.727 What do they use it for? 49:26.733 --> 49:31.973 2/3 of it is used to make that compound, just add water in 49:31.967 --> 49:35.167 the reaction that we were just talking about, 49:35.167 --> 49:36.627 to make that compound. 49:36.633 --> 49:38.503 Does anybody know what that compound is called? 49:38.500 --> 49:39.770 You could call it dihydroxyethane. 49:42.733 --> 49:46.173 But, it has a more common name. 49:46.167 --> 49:48.767 It's called ethylene glycol. 49:48.767 --> 49:49.767 It's antifreeze. 49:49.767 --> 49:52.527 So, a lot of it is used for antifreeze, but it's also used 49:52.533 --> 49:53.503 it for solvent. 49:53.500 --> 49:59.830 Also it's incorporated in polymers, the polyethylene 49:59.833 --> 50:02.833 terephthalate, the stuff that makes soft drink 50:02.833 --> 50:04.303 bottles, for example. 50:04.300 --> 50:06.970 It's used in making that. 50:06.967 --> 50:08.597 Glycol is an interesting word. 50:08.600 --> 50:14.170 The gly- is from Greek root that means sweet, like 50:14.167 --> 50:17.227 glucose, it's the same root. 50:17.233 --> 50:20.873 It's because ethylene glycol tastes sweet, although we 50:20.867 --> 50:24.727 don't taste it because it's poisonous, but the original 50:24.733 --> 50:26.533 people did, so that's why it's called glycol. 50:29.767 --> 50:34.767 That reaction, to change ethylene oxide into ethylene 50:34.767 --> 50:39.567 glycol, occurs either with base catalysis or acid 50:39.567 --> 50:45.367 catalysis, so since the focus of this lecture has been-- 50:45.367 --> 50:49.227 woops, this lecture is over. 50:49.233 --> 50:51.003 Sorry, I got carried away. 50:51.000 --> 50:53.070 We'll talk about the mechanisms next time. 50:53.067 --> 50:54.327 Thanks.