Asymmetric Synthesis and Properties of Sulfinimines (Thiooxime S-Oxides)

Abstract

Enantiomerically pure sulfinimines (thiooxime S-oxides 10), important building blocks in the asymmetric synthesis of amine derivatives, are prepared in good to excellent yields in one step from aromatic, heteroaromatic, and aliphatic aldehydes. This protocol involves treating commercially available (R)- or (S)-menthyl p-toluenesufinate (Andersen reagent 4) with LiHMDS, followed by the aldehyde, affording (E)-10 exclusively. The sulfinimines 10 are formed via a Peterson-type olefination reaction of silylsulfinamide anion 13 with the aldehyde. Anion 13 is generated by reaction of lithium menthoxide (12a) with bis(trimethylsilyl)sulfinamide 11, which is formed in the reaction of 4 with LiHMDS. The other product formed is O-(trimethylsilyl)menthol (12c), which is isolated in >80% yield for recycling. Two other less efficient methods for the asymmetric synthesis of 10 are discussed: (i) the asymmetric oxidation of sulfenimines 6 with chiral nonracemic oxaziridines and (ii) the reaction of metal aldimines, prepared from nitriles, with 4. All of these protocols fail with ketones.

Stereoselective Radical Addition of an Acetal to Sterically Tuned Enantiomerically Pure N-Sulfinyl Imines

“…30) The obtained structures were in good agreement with an X-ray structure of 1a 31) and those calculated for simpler N-sulfinyl imines. [32][33][34] Thus, in all of these N-sulfinyl imines, the azomethine substituents are trans to the N-S bond while the S-O bond and the CϭN bond are eclipsed.…”

Formation of Cyclic Sulfinates and Sulfinamides through Homolytic Substitution at the Sulfur Atom

“…Sulfinates [22,23] and sulfinamides [24][25][26] play pivotal roles in modern asymmetric synthesis as key precursors of chiral molecules. As part of our program devoted to new reactions involving sulfur-based moieties, [27][28][29][30] we became interested in the synthesis of cyclic sulfinates and sulfinamides because they are versatile synthetic intermediates, [31,32] and have elicited interest in medicinal chemistry.…”

Synthesis of Nonracemic α-Trifluoromethyl α-Amino Acids from Sulfinimines of Trifluoropyruvate

“…[15] The breakthrough in the field is probably represented by the work of Davis, [16] who disclosed a very convenient onepot method for the preparation of enantiopure sulfinimines. Thus, this methodology initially formed the basis for our attempted synthesis of the desired sulfinimine of trifluoropyruvate 1, but all our efforts met with failure.…”

“…Key: i) (Me 3 Si) 2 NLi, THF; ii) CF 3 COCOOEt However, it proved possible to prepare the key sulfinimines (S)-1a and (S)-1b efficiently by a different pathway; namely by Staudinger (aza-Wittig) reaction, [18] which is known to be an extremely useful tool for preparing imines with a strongly electrophilic character (Scheme 4). Thus, the p-tolylsulfinamide (S)-7, easily obtained as described by Davis, [16] was treated with PPh 3 /DEAD in dry THF at room temp., [19] affording in good yield (92%) the chiral Staudinger reagent (S)-8, formerly obtained only in racemic form and with low yields from Ph 3 PϭNH, p-Tol-SOCl, and triethylamine. [20] Enantiomeric (R)-8 was obtained from (R)-7 in identical fashion.…”

“…Neat DEAD (1.95 mL, 12.35 mmol) was added dropwise at 0°C, with stirring, to a solution of (S)-7 [16] (1.93 g, 12.35 mmol) and PPh 3 (3.24 g, 12.35 mmol) in dry THF (50 mL). The resulting dark red mixture was allowed to warm to room temp.…”