Oxazoline‐Based Organocatalyst for Enantioselective Strecker Reactions: A Protocol for the Synthesis of Levamisole

Abstract

A chiral oxazoline-based organocatalyst has been found to efficiently catalyze asymmetric Strecker reactions of various aromatic and aliphatic N-benzhydrylimines with trimethylsilyl cyanide (TMSCN) as a cyanide source at -20 °C to give α-aminonitriles in high yield (96 %) with excellent chiral induction (up to 98 % ee). DFT calculations have been performed to rationalize the enantioselective formation of the product with the organocatalyst in these reactions. The organocatalyst has been characterized by single-crystal X-ray diffraction analysis, as well as by other analytical methods. This protocol has been extended to the synthesis of the pharmaceutically important drug molecule levamisole in high yield and with high enantioselectivity.

Oxazoline derivatives tagged with tosylated amino acids as recyclable organocatalysts for enantioselective allylation of aldehydes

“…organocatalysts 1-5 with varied chirality (Scheme 1). 15,17 We also synthesized catalyst (S,S)-6 (Scheme 2) by replacing the tosyl part of the catalyst (S,S)-4 with Boc to ascertain the role of the tosyl group in the allylation reaction.…”

“…However, there are nagging issues, such as the extremely low reaction temperatures, moderate yield and ee, and nonrecyclability of these catalysts, which need to be addressed. Bearing in mind the value of oxazolines, overall stability of the catalyst and our previous experience with tosylated amino acids 15 as organocatalysts in the enantioselective allylation reaction of aldehydes, herein we have synthesized a series of oxazoline-based organocatalysts, 16,17 (S,S)-1 to (S,S,R)-5, featuring sulfonamide groups with varying steric features and two to three chiral centers. Chiral centers in organocatalysts featuring congurations with different permutations and combinations were prepared for their possible role in inuencing the product enantioselectivity.…”

Biocatalytic Approach to Chiral β-Nitroalcohols by Enantioselective Alcohol Dehydrogenase-Mediated Reduction of α-Nitroketones

“…It is also one of the nonspecific immunomodulating agents that are used in clinical practice [35][36][37]. The known synthetic asymmetric approaches are based on the use of optically active phenylethylenediamine [38][39][40][41] or amino alcohol (S)-2a as intermediates [42].…”

Understanding the mechanism of procedure-controlled enantioselectivity switch in cinchona alkaloid thiourea catalyzed [3+2] cycloaddition: H-bonds controlled enantioselectivity

“…A variety of new chiral compounds have been synthesized as organocatalysts and showed high efficiency, excellent selectivity and great universality . Among these catalysts, the bifunctional systems [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41], which mimic the natural enzymes, can bind with the substrates on two sites, so are usually more effective. Lately cinchona alkaloid based aminothiourea catalysts, one kind of bifunctional catalysts, are applied in a series of asymmetric reactions and exhibit excellent stereoselectivity [42][43][44][45][46][47][48][49].…”