CHEM 125b - Lecture 37 - Proving the Configuration of Glucose and Synthesizing Two Unnatural Products

Modern spectroscopic tools show not only the constitution, configuration, and conformation of glucose but also how it interconverts between isomeric hemiketal pyranose rings. One of mankind’s great accomplishments was determinining its constitution and especially its configuration before such spectroscopy. By 1887 Heinrich Kiliani had established the constitution of glucose as an aldohexose, and with help from Emil Fischer, he developed a method for homologating aldoses.

CHEM 125b - Lecture 36 - α-Reactivity and Condensation Reactions

As in many synthetic procedures, an important challenge in ketone alkylation is choosing reagents and conditions that allow control of isomerism and of single vs. multiple substitution. β-Dicarbonyl compounds allow convenient alkylation and preparation of ketones and carboxylic acids. The aldol condensation, in which an α-position adds to a carbonyl group to generate a β-hydroxy- or an α,β-unsaturated carbonyl compound, can be driven to completion by removal of water. The Robinson annulation reaction is an important example of conjugate addition to α,β-unsaturated carbonyl compounds.

CHEM 125b - Lecture 35 - Acyl Insertions and α-Reactivity

When a nucleophilic atom bearing a good leaving group attacks a carbonyl group, an adjacent Rgroup can migrate to the new atom, inserting it into the R-acyl bond. This mechanism can insert O, NH, or CH2 groups into the acyl bond with informative stereospecificity in the case of the Beckmann rearrangement of oximes. Although the migrating groups are formally anionic, relative migratory aptitudes show that they give up electron density during rearrangement.

CHEM 125b - Lecture 34 - Acids and Acid Derivatives

Reactions of carboxylic acids and their salts include nucleophilic substitution and decarboxylation to leave enols, free radicals, or alkyl halides. A review of the IR spectroscopy of acid derivatives includes the use of vibrational coupling in the structure determination of anhydrides and imides. Many acid derivatives can be interconverted by substitution through a tetrahedral intermediate, and differences in acidity can be used to drive such reactions toward completion. Reduction of acid derivatives illustrates the challenge of designing selective reactions.

CHEM 125b - Lecture 33 - Green Chemistry; Acids and Acid Derivatives

Green chemistry needs new asymmetric reactions and safer, more environmental Mitsunobu reactions. The Mitsunobu mechanism is general and reliable, but atom inefficient, generating almost 30 times as much weight of by-products as of the water it is designed to eliminate. Admirably green processes include autoxidation of aldehydes to carboxylic acids using only O2, and oxidation of alcohols by loss of H2 using a ruthenium catalyst.

CHEM 125b - Lecture 32 - Measuring Bond Energies: Guest Lecture by Prof. G. Barney Ellison

Spectroscopic determination of bond dissociation energies is relatively straightforward for many diatomic molecules, but for polyatomic molecules it requires merging the results from a variety of challenging experiments. Professor Ellison describes how such techniques as flowing-afterglow mass spectroscopy and negative-ion photoelectron spectroscopy together with data on free-radical kinetics and heats of formation have allowed precise determination of the O-H, C-H, and C-O bonds in methanol and other compounds.

CHEM 125b - Lecture 31 - Periodate Cleavage, Retrosynthesis, and Green Chemistry

The ability of periodic acid (HIO4) to cleave the C-C bond of vicinal diols and α-hydroxycarbonyl compounds allowed structure determination of sugars and their ketals before spectroscopy was available. Reduction of carbonyl compounds by organometallic or hydride reagents provides a range of schemes for synthesizing various alcohols, where preference may be dictated by the desire to avoid competing processes. Wittig olefination allows conversion of C=O to C=C with good control over constitutional isomerism.

CHEM 125b - Lecture 30 - Oxidation States and Mechanisms

A difficult exam question shows how visible and NMR spectroscopy related to long-term misassignment of the structure for the triphenylmethyl dimer. Evidence from 1970 shows that Friedel-Crafts propylation involves an SN2 mechanism, not a protonated cyclopropane. Assigning oxidation states from -4 to +4 to the carbon atoms of proposed starting material and product allows choosing whether a reagent that is oxidizing or reducing or neither is appropriate. Beyond belonging to the appropriate redox class, the reagent must have an appropriate mechanism.

CHEM 125b - Lecture 29 - Imines and Enamines; Oxidation and Reduction

Imines are pervasive in chemistry and biology, playing key roles both the in artificial Strecker synthesis of amino acids and their biosynthesis by L-glutamate dehydrogenase and by transamination. Imines are also involved in Stork’s α-alkylation and acylation of ketones by way of enamine intermediates. Oxidation and reduction in organic chemistry can involve actual electron transfer, when ion-radical intermediates are involved as in the formation of Grignard reagents or in the pinacol reduction.

CHEM 125b - Lecture 28 - Mechanism and Equilibrium of Carbonyl Reactions

This lecture aims at developing facility with devising plausible mechanisms for acid- and base-catalyzed reactions of carbonyl compounds, carboxylic acids, and their derivatives. When steric hindrance inhibits the A/D mechanism of Fischer esterification, an acid-catalyzed D/A mechanism can still occur. Substituent influence on the equilibrium constants for carbonyl hydration demonstrates four effects: bond strength, steric, electron withdrawal, and conjugation.

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