TiCl₄‐Promoted Asymmetric Aldol Reaction of Oxazolidinones and its Sulphur‐Congeners for Natural Product Synthesis

Abstract

Nature is incessantly affianced to construct bioactive and structurally intriguing compounds with magnificent three‐dimensional frameworks in the Universe. The inadequacy of these naturally occurring precious compounds prompted several minds of chemists to synthesise them in a laboratory for a thorough evaluation of their medicinal and clinical properties via a structure‐activity relationship study. Finding an optimised methodology to synthesise chiral natural products has always been challenging in synthetic organic chemistry, particularly the formation of asymmetric carbon‐carbon bonds adhering to the existing stereochemistry. In this context, chiral auxiliaries have proven to be effective tools for inducing chirality during the synthesis of chiral molecules. In fact, the chiral auxiliary will allow us to control the synthesis of many enantiomerically pure isomers in natural product synthesis. In this area, the significant contribution of the Evans’ chiral auxiliary in TiCl4‐mediated asymmetric aldol reactions to the installation of known configurations in organic synthetic chemistry motivated us to compile an exhaustive and systematic summary of the relevant research findings published in the last two decades.

Azide‐free Enantioselective Synthesis of Clinical Antibiotic (1R,2R)‐Chloramphenicol (Chloromycetin)

“…The N‐(N‐Boc glycinyl) oxazolidinone 2 , [10f] synthesized from chiral auxiliary 1 , served as the chiral synthon for the synthesis of the targeted chloramphenicol and its isomer. In the 1 H NMR spectrum of N‐(N‐Boc glycinyl) oxazolidinone 2 , the peak at δ 1.45 ppm corresponds to the tert ‐butyl group of glycine, and the signals between δ 7.43–7.11 ppm are attributed to the phenyl group of benzyl oxazolidinone, confirming its structure.…”

The Synthesis of 3-(R)- and 3-(S)-Hydroxyeicosapentaenoic Acid

“…In this paper, the total synthesis of both enantiomers of 2 is presented, using acetate aldol methodologies. This methodology is of current interest in the total synthesis of natural products [ 40 ]. Sufficient amounts of materials for conducting biological and biosynthetic studies are now available.…”

Evans’ Chiral Auxiliary‐Based Asymmetric Synthetic Methodology and Its Modern Extensions

“…The reaction features excellent and predictable syn ‐diastereoselectivities, [7a] which was referred as “Evans syn ” aldol. The value of this method was demonstrated by the application to the total synthesis of many nature products [14c–e] . Subsequently, the employment of N ‐acyloxazolidinones 2 for the asymmetric alkylation (Scheme 1b) [7b] and Diels‐Alder cycloaddition (Scheme 1c) [7c] was achieved.…”