Novel Stereoselective Synthesis of Functionalized Oxazolidinones from Chiral Aziridines

Abstract

Enantiomerically pure N-(R)-alpha-methylbenzyl-4(R)-(chloromethyl)oxazolidinones (4R)-5a-k were synthesized in one step and high yields from various aziridine-2-methanols (S)-2a-k by intramolecular cyclization with phosgene. The alpha-methylbenzyl substituent on the nitrogen was easily cleaved to give both enanatiomers of 4-(chloromethyl)oxazolidinones (R)-7a and (S)-7a. (R)-7a was used for the efficient syntheses of (L)-homophenylalaninol analogues (S)-12a-j. We also applied the same methodology to prepare oxazolidinones 9a-c containing a heteroatom-substituted alkyl group at C-4 in high yields.

Molecular Basis for the Stereoselective Ammoniolysis of N‐Alkyl Aziridine‐2‐Carboxylates Catalyzed by Candida antarctica Lipase B

“…Hydrogenolysis or metal-ammonia reduction can remove the (R)-or (S)-methylbenzyl substituent. [15] For CAL-B-catalyzed reactions of secondary alcohols, the classical paradigm of exchange-of-substituents works well. The substituents bind in the large pocket and medium pocket (also called the stereoselectivity pocket) that form the alcohol-binding site.…”

Ring Expansions of Nonactivated Aziridines and Azetidines

“…Functionalized aziridines with a hydroxymethyl group 29 can be expanded to chloromethyl oxazolidinones 31 upon reaction with NaH and phosgene [34]. This reaction is of high synthetic relevance, since the starting substrates can be prepared quite easily in enantiomerically pure form.…”

Three‐Membered Heterocycles. Structure and Reactivity

“…Thus, in the presence of sodium iodide, Boc anhydride serves as a carbon dioxide surrogate in the conversion of the ( þ )-pseudoephedrine-derived aziridine 141 into oxazolidinone 143, in which the stereochemistry of the ring substituents is preserved [210,211]. Hydroxymethylaziridines (e.g., 144) can be bridged with phosgene into labile fused bicyclic oxazolidinone structures (i.e., 145), which undergo in situ nucleophilic attack by chloride to give chloromethyloxazolidinones (e.g., 146) in excellent yield [212]. Also, gaseous carbon dioxide itself can be trapped by aziridines at atmospheric pressure using lithium bromide as a catalyst, as shown by the conversion of arylaziridine 147 into the corresponding oxazolidinone 148.…”