On the utility of S-mesitylsulfinimines for the stereoselective synthesis of chiral amines and aziridines

Abstract

The synthetic utility of S-mesitylsulfinimines for the synthesis of chiral amines and aziridines was examined through their reactions with Grignard reagents, with the ylides derived from trimethylsulfonium iodide and S-allyl-tetrahydrothiophenium bromide and through an aza-Darzens manifold, affording convenient access to a diverse range of highly substituted chiral amines and aziridines in high yields and excellent stereoselectivities.

3-Arylaziridine-2-carboxylic Acid Derivatives and (3-Arylaziridin-2-yl)ketones: The Aziridination Approaches

“…There are chiral N-phosphinyl imines 2f1 , 2f2 [ 60 , 61 ] and chiral sulfimines 2f3 , 2f4 [ 62 , 63 , 64 ] presented ( Scheme 13 ). N-phosphinyl imines 2f1 have been successfully used in aza -Darzen reaction with enolates generated from esters 15b in ten examples of aziridines cis - 1a7 in 72–82% chemical yields and >80% de [ 60 ].…”

“…Corresponding 3-aryl and 3.3-diaryl products were obtained in moderately good cis -selectivity (71:29–98:2); eight examples of 3-aryl products cis - 1a7 were demonstrated. Isolated examples of S-mesitylsulfinyl imines 2f4 have been employed in aziridine cis - 1a7 synthesis [ 63 ]. Trisubstituted 3-aryl aziridine-2-carboxylates cis - 1a7 were obtained from substituted 2-bromoesters 15b and tert -butane sulfinyl aldimines 2f3 [ 64 ] in >60% chemical yields and >98% de (five examples).…”

“…There are chiral N-phosphinyl imines 2f1, 2f2 [60,61] and chiral sulfimines 2f3, 2f4 [62][63][64] Chemical yields are good (57-78%) and stereoselectivity excellent, >95% dr in 14 demonstrated examples [58]. However, in some cases depending of the imine aryl substituent structure (using imines 2e2) inversion of stereochemistry has been observed and aziridines trans-1b5 obtained [59].…”

“…There are chiral N-phosphinyl imines 2f1, 2f2 [60,61] and chiral sulfimines 2f3, 2f4 [62][63][64] Modified aza-Darzen type protocol allows to obtain trisubstituted spirocyclic 3-aryl aziridinyl ketones 1c3 (Scheme 14) from cyclic halogenated ketones 15c illustrated in the Scheme 14 [65]. Two protocols-one-step direct approach to ketones 1c3 (Scheme 14) and two-step synthesis through an addition product, namely, tertiary halogenide 16 (Scheme 14) -were realized.…”

Highly diastereoselective radical cyclisations of chiral sulfinimines

“…Initially introduced by Davis, 11 we have found that they offer selectivity near that of the hindered tert-butanesulfinimines, but offer complementary reactivity in Grignard additions, giving high diastereoselectivities in an open-transition state addition. 12 Furthermore, the mesityl group can be more easily removed, which can be useful for particularly sensitive substrates such as N-sulfinyl aziridines. 10,11 We recently reported a convenient one-pot procedure for the synthesis of mesitylsulfinimines in >99% ee using a phenyl alanine-based template, 13 and thus they are also readily available substrates.…”