Diastereoselective Synthesis of S-tert-Butyl-β-(trifluoromethyl)isocysteine

Abstract

Both diastereoisomers of S-tert-butyl-beta-(trifluoromethyl)isocysteine have been synthesized stereoselectively by the sequential reactions of trifluoroacetimidoyl chloride with the lithium enolate of tert-butyl alpha-tert-butylthioacetate, followed by the diastereoselective reduction of the imino group with sodium borohydride in the presence of zinc(II) or di(ethylene glycol) dimethyl ether, and finally by the deprotection of N-aryl and tert-butyl ester groups.

Stabilization of a hydrophobic recombinant cytokine by human serum albumin

“…Consequently, chelated intermediates formation appeared far less efficient for iminoesters 1a , 1b than for ketoesters 2a , 2b , 2c . This is in contradiction with previous results described in the literature but nevertheless for less hindered imino and enaminoesters 34, 36. In our case, the stereochemical outcome of the reduction reaction affording the major anti diastereomer 5a , 5b could be explained assuming a predominantly non chelated Felkin Anh model: the presence of both hindered methylbenzyl moiety on the imino group and the quaternary carbon atom in the α‐position prevents the formation of the cyclic chelated intermediate.…”

“…However, the presence of the chiral imine part caused a global improvement of diastereoselectivity, comparatively to the corresponding ketoesters. We can also note that a ZnCl 2 /NaBH 4 mixture33, 34 instead of freshly prepared Zn(BH 4 ) 2 did not modified neither diastereoselectivity nor chemical yield (Entries 5 and 6).…”

Asymmetric reduction of β‐ketoesters and chiral β‐iminoesters: Impact of a α‐quaternary stereocenter

“…34,36 In our case, the stereochemical outcome of the reduction reaction affording the major anti diastereomer 5a-b could be explained assuming a predominantly non chelated Felkin Anh model: the presence of both hindered methylbenzyl moiety on the imino group and the quaternary carbon atom in the a-position prevents the formation of the cyclic chelated intermediate. Furthermore, with bulkier reducing agents, we observed a matched pair effect in the (R,S)-diastereomer 1 0 b (Entries 7 and 8 versus 11 and 12) which became a mismatched effect with chelating reducing agent (Entry 5 versus 10) (Scheme 3).…”

A novel conformationally restricted analogue of 3-methylaspartic acid via stereoselective methylation of chiral pyrrolidin-2-ones

“…15 Under these conditions cleavage of the 4-methoxyphenylethyl group occurred, to give in good yield the enantiomerically pure 3,4,4-trisubstituted pyrrolidin-2-ones 3a,b, both protected forms of a conformationally restricted analogue of b-methylaspartic acid, 1 (Scheme 1).…”