A Novel Route to Chiral trans‐6‐Alkyl‐2‐hydroxymethyl‐1,2,5,6‐tetrahydropyridines by Allylation of Chiral Imines and Ring‐Closing Metathesis − Total Synthesis of (−)‐3‐epi‐Deoxoprosopinine

Abstract

A novel route to enantiomerically pure trans-6-alkyl-2-hydroxymethyl-1,2,5,6-tetrahydropyridines is reported in five steps from Garner's aldehyde with overall yields higher than 35 %. This strategy is based on the allylation of chiral imino alcohols formed in situ followed by a ring-closing metathesis.

Recent Advances in the Total Synthesis of Piperidine Azasugars

“…However, ring-opening of the epoxide 140 was efficiently performed under basic conditions, and subsequent removal of the protecting groups provided the 1-deoxyidonojirimycin 144 as the unique diastereoisomer in 87 % overall yield from 140. Finally, stereoselective dihydroxylation of tetrahydropyridine 139 under modified Upjohn conditions afforded the diol 145 as a single diastereoisomer in 85 % yield, which was converted into 1-deoxygulonojirimycin (70) in good yield following the sequence previously described for other congeners. Thus, the three DNJ analogs 144, 11, and 70 were obtained in 31 %, 15 %, and 28 % overall yield, respectively, from d-Garner's aldehyde.…”

“…As a first step in this program, we have very recently described a synthesis of 5-deoxyadenophorine (146) [69] (Scheme 20) using a novel strategy [70] to build chiral trans-2,6-disubstituted-1,2,5,6-tetrahydropyridines.…”

“…O'Doherty et al have described an elegant access to various chiral azasugars based on the Sharpless AA and an aza-Achmatowicz rearrangement, as illustrated in Scheme 25 for the synthesis of 1-deoxygulonojirimycin (70). [86] Vinyl furan 184 was prepared by addition of furfural to an ethereal solution of TMSMgCl followed by acidic treatment of the resulting alcohol.…”

First Total Synthesis of (+)‐Adenophorine, a Naturally Occurring Inhibitor of Glycosidases

“…As part of our ongoing program involving the synthesis of alkaloids, we have developed an efficient route to chiral trans-6-alkyl-2-hydroxymethyl-1,2,5,6-tetrahydropyridines. [10] First Total Synthesis of the Glycosidase Inhibitor (+)-Adenophorine Scheme 1. Retrosynthetic analysis.…”

“…[10,11] In our strategy, the configuration of each stereogenic center has to be controlled during the building steps. We planned to construct the piperidine moiety and to introduce the three hydroxy groups diastereoselectively by applying key reactions as depicted in the retrosynthetic Scheme 1: diastereoselective allylation of imine 9, ring-closing metathesis reaction to build the trans-2,6-disubstituted 1,2,5,6-tetrahydropyridine skeleton 11, and an olefination step following the oxidation of the selenide 13.…”