Asymmetric Synthesis and Reactions of cis-N-(p-Toluenesulfinyl)aziridine-2-carboxylic Acids

Abstract

cis-Aziridine-2-carboxylic acids, 2, precursors of the difficult to prepare syn-8-hydroxy-a-amino acid structural unit, are prepared in high diastereomeric purity by a Darzens-type reaction of the lithium enolate of methyl bromoacetate with enantiopure sulfinimines 1.The regio-and stereoselective ring-opening reactions of N-activated cis-and tra.ans-aziridine-2-carboxylic acids play increasingly important roles in strategies for the synthesis of natural and unnatural amino acids.lP2 While racemic aziridines are readily available, procedures for their synthesis in enantiomeric pure form are limited.3 This is particularly true for cis-aziridine-2-carboxylic acids, precursors of the difficult to prepare syn-8-hydroxy-a-amino acid structural unit found in many bioactive materiaha Preparations of nonracemic cis-aziridine-2-carboxylic acids include (i) cyclization of synthetic7 and naturally occurring 8-hydroxy-a-amino acids: (ii) the diastereoselective reaction of ammonia with nonracemic a-bromo-a,@-unsaturAbstract published in Aduance ACS Abstracts, March 15, 1994. (1) For examples of the application of aziridine-2-carboxylic acids to the Synthesis of a-amino acida see: (a) Baldwin, J. E.; Spivey, A. C.; Schodield, C. J.; Sweeney, J. B. Tetrahedron 1993,49,6309. (b) Legtem, J.; Thijs, L.; Zwanenburg, B. Recl. Trau. Chim. Pays-Bas 1992,111,16. (c) Shima, I.; Shimazaki, N.; Imai, K.; Hemmi, K.; Hashimoto, M. Chem.

Iodine(III)‐Mediated Preparations of Nitrogen‐Containing Sulfur Derivatives: Dramatic Influence of the Sulfur Oxidation State

“…Sulfinamides are easily oxidized by electrophilic oxidants, which make their lone pair relatively nucleophilic. [47] Alternatively, D could undergo a competitive three-atom rearrangement similar to the one evidenced by Reggelin and coworkers (path b). [61] In Reggelin×s case, the oxidation of sulfinamides by tert-butyl hypochlorite leads to a sulfonimidoyl chloride by initial N-halogenation, which is subsequently substituted by the alcohol with inversion.…”

Asymmetric Synthesis of α-Substituted-β-Amino Phosphonates and Phosphinates and β-Amino Sulfur Analogs

“…44a Interestingly, the exclusive (R)-absolute induction at C-2 in the formation of 63 and 64 is opposite to that found in the analogous carboxylic ester case, 45 and the same as that observed for the addition of phosphites 46 and a-phosphonates carbanions 7 to (S)-39. Whereas the selectivity for metal enolate additions to sulfinimines has been rationalized in terms of chairlike transition states where the metal is coordinated to both the sulfinyl oxygen and imine nitrogen, 45,47 transition-state rationales for phosphine and a-phosphonate carbanion additions to (S)-39 have these species reacting from the least hindered direction, that is, opposite to the p-tolylsulfinyl group. 7,46 This difference may reflect the greater steric bulk of metal phosphonate anions compared to enolates as well as their tetrahedral structure.…”

The 3‐(3‐Pyridine)propionyl Anchor Group for Protease‐Catalyzed Resolutions: p‐Toluenesulfinamide and Sterically Hindered Secondary Alcohols

“…This addition yields the N-alkylsulfinamide, which upon hydrolysis of the S À N link yields an amine. Enantioselective syntheses using p-toluenesulfinimine include preparations of amines, [31] a-and b-amino acids, [30] aziridines [32] and aminophosphonic acids. [33] This enzyme-catalyzed route to enantiopure p-toluenesulfinamide 1 using the 3-(3-pyridine)propionyl group compares well with current chemical routes to sulfinamides.…”