Additions of Enantiopure α-Sulfinyl Carbanions to (S)-N-Sulfinimines:  Asymmetric Synthesis of β-Amino Sulfoxides and β-Αmino Alcohols

Abstract

The addition of the lithium anions derived from (R)- and (S)-methyl and -ethyl p-tolyl sulfoxides to (S)-N-benzylidene-p-toluenesulfinamide provides an easy access route to enantiomerically pure beta-(N-sulfinyl)amino sulfoxides. Stereoselectivity can be achieved when the configurations at the sulfur atoms of the two reagents are opposite (matched pair), thus resulting in only one diastereoisomer, even for the case in which two new chiral centers are created. The N-sulfinyl group primarily controls the configuration of the carbon bonded to the nitrogen, whereas the configuration of the alpha-sulfinyl carbanion seems to be responsible for the level of asymmetric induction, as well as for the configuration of the new stereogenic C-SO carbon in the reactions with ethyl p-tolyl sulfoxides. An efficient method for transforming the obtained beta-(N-sulfinyl)amino sulfoxides into optically pure beta-amino alcohols, based on the stereoselective non-oxidative Pummerer reaction, is also reported.

Application of chiral sulfoxides in asymmetric synthesis

“…The behavior of enantiomerically pure sulfinylimines with chiral α-sulfinyl carbanions has been reported by Garcia Ruano et al 40 The highest Stereoselectivity is achieved when the configuration at the sulfur atoms of the two reagents are opposite (matched pair), affording only one diastereoisomer (Figure 15). For each pair, the major diastereoisomer has identical configuration at the new stereogenic carbon (R in both case), despite the opposite configuration of the sulfoxide used as nucleophile in each case.…”

Recent developments in chiral non-racemic sulfinyl group chemistry in asymmetric synthesis

“…The behaviour of enantiomerically pure sulfinyl imines with non racemic chiral α-sulfinyl carbanions has been reported by Bravo et al 54 The highest stereoselectivity is achieved when the configuration at the sulfur atoms of the two reagents are opposite (matched pair), affording only one diastereoisomer (Scheme 24). For each pair, the major diastereoisomer has identical configuration at the new stereogenic carbon (R in both case), despite the opposite configuration of the sulfoxide used as nucleophile in each case.…”

Synthesis of “Trioxaquantel”® Derivatives as Potential New Antischistosomal Drugs

“…Nevertheless, the formation of sulfinate 31 in good yield, followed by its rapid degradation, cannot be definitively ruled out. [46,47] In any case, this method was abandoned. In a next attempt, (Ϯ)-3 was quantitatively transformed into diastereomeric carbamates 32 by treatment with (-)-menthyl chloroformate in the presence of triethylamine (Scheme 10,b).…”