I. The Disastereoselective Alkylation of Chiral 2-Oxazolidinone Imide Enolates. II. Efforts Directed Toward the Enantioselective Total Synthesis of Ferensimycin B

Citation

Mathre, David John (1985) I. The Disastereoselective Alkylation of Chiral 2-Oxazolidinone Imide Enolates. II. Efforts Directed Toward the Enantioselective Total Synthesis of Ferensimycin B. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/x5a5-z913. https://resolver.caltech.edu/CaltechTHESIS:02202019-093314396

Abstract

The diastereoselective alkylation of chiral 2-oxazolidinone imide enolates is described. The requisite chiral N-acyl 2-oxazolididones are prepared from readily available amino acid and amino alcohol precursors. The lithium and sodium enolates, derived from these chiral imides, react in a highly diastereoselective manner with a variety of electrophiles. Furthermore, the diasteromers are often separable by liquid chromateography affording products with a diastereomeric purity ≥ 99:1. Several methods are described for the non–destructive removal of the chiral auxiliary to afford enantiomerically pure alcohols, aldehydes, carboxylic acids, acid chlorides, esters, hydrazides, and ketones. Through the use of chiral imides 16 and 20 either of the enantiomeric products can be obtained.

[Structural formula. See abstract in scanned thesis for details.]

An approach to the enantioselective total synthesis of the poly- ether ionophore antibiotic ferensimycin B (2) is described. The synthesis employs the diastereoselective alkylation and aldol condensation of chiral 2-oxazolidinone imide enolates to both construct the carbon backbone and generate the necessary stereo- centers. This research has culminated in the preparation of the advanced intermediate 49.

[Structural formula. See abstract in scanned thesis for details.]

An enantioselective total synthesis of (R) and (S)-thiorphan [N-(1-oxo-2-mercaptomethyl-3-phenylpropyl)glycine] via a six-step sequence is reported. The key step, establishing the absolute stereochemistry, is the diastereoselective alkylation of the enolate derived from chiral 2-oxazolidinone imide 16 (R = PhCH₂) or 20 (R = PhCH₂) with benzyl bromomethyl sulfide. The level of alkylation diastereoselection is in excess of 95:5.

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