Enantioselective Synthesis of Highly Functionalized 4‐Piperidones by the Asymmetric Imino‐Diels–Alder Reaction of Chiral 2‐Amino‐1,3‐Butadienes

Abstract

Chiral2-amino-I ,3-butadienes 1 derived from commercially available (S)-2-methoxymethylpyrrolidine react with aromatic N-trimethylsilylaldimines and Nphenylaldimines in the presence of ZnC1, to give, after the reaction workup, 4-piperidones 4 and 6, respectively, with moderate to very high enantiomeric excesses. In addition, the absolute configurations of derivatives of 4 a and 4g were determined by circular dichroism and NMR spectroscopy on the Mosher ester, respectively. asymmetric

A Novel Approach to the Enantioselective Synthesis of Nuphar Alkaloids: First Total Synthesis of (−)-(5S,8R,9S)-5- (3-Furyl)-8-methyloctahydroindolizidine and Total Synthesis of (−)-Nupharamine

“…On the other hand, in the recent years, we have been interested in exploring the synthetic applications of chiral 2-amino-1,3-butadienes in asymmetric Diels−Alder cycloadditions. We have previously shown that chiral 2-aminodiene 3 reacts with aromatic N -trimethylsilylaldimines 4 in the presence of ZnCl 2 to afford, after mild hydrolysis of the [4 + 2] cycloadduct, 4-piperidones 5 with high to very high enantiomeric excesses (Scheme ) …”

The synthesis and biological activity of the marine metabolite cylindrospermopsin

“…In 1998, Barluenga et al described the synthesis of a similar A-ring model for cylindrospermopsin 1 (Scheme 12), 38 The approach taken was based upon their previously reported 39 methodology for the enantioselective synthesis of functionalised 4-piperidones by [4 + 2] cycloaddition of N-silylaldimines with chiral 2-aminobuta-1,3-dienes. For example, reaction of diene 102 with trimethylsilylaldimine 103 in the presence of ZnCl 2 gave 4-piperidone 104.…”

Cycloadditions in synthesis

“…424 Barluenga has used the diene 97 derived from (S)-2-methoxymethylpyrrolidine in syntheses of highly functionalised 4-piperidones. 425 Saito has extensively investigated the asymmetric hetero-Diels-Alder reactions of thiochalcones (e.g. 98) by examining thermal and Lewis acid catalysed reactions with di-(Ϫ)-menthyl fumarate, 426 with (S)-N-acryloyl-4-benzyl-1,3-oxazolidin-2-one under ytterbium() triflate, 427 dimethylaluminium chloride 428 or titanium() chloride 428 catalysis and with N-acryloyl-1,3oxazolidin-2-one using a homochiral copper() bis(imine) catalyst.…”