A Route to "all-cis" 2-Methyl-6-Substituted Piperidin-3-ol Alkaloids from syn-(2R,1′S)-2-(1-Dibenzylaminomethyl)epoxide: Rapid Total Synthesis of (+)-Deoxocassine

• Published in: European Journal of Organic Chemistry Vol. 2012; no. 1; pp. 62 - 65
• Main Authors: Geant, Pierre-Yves, Martinez, Jean, Salom-Roig, Xavier J.
• Format: Book Review Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.01.2012; WILEY‐VCH Verlag; Wiley; Wiley-VCH; Wiley-VCH Verlag
• Subjects: Alkaloids; Amination; Chemical Sciences; Chemistry; Chemistry, Organic; Epoxides; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Hydraz­ones; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; Total synthesis; ACID; Hydrazones; (-)-DEOXOCASSINE; (-)-CASSINE; Total synthesis; ENANTIODIVERGENT; Alkaloids; CYCLOADDITION; PROSOPIS; Amination; REDUCTION; LACTONES; CASSIA; STEREOSELECTIVE-SYNTHESIS; Epoxides; Intramolecular reaction; Nitrogen heterocycle; Lithium; Oxygen heterocycle; Ring cleavage; Hydrolysis; Chemical reduction; Alkaloid; All cis stereoisomer; Piperidine derivatives; Epoxide; Oxirane derivatives; Hydrazone; Chemical synthesis; Enolate; Nucleophile
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201101333

A general strategy leading to the synthesis of two cis‐2‐methyl‐6‐substituted piperidin‐3‐ols is described. syn‐(2R,1′S)‐2‐(1‐Dibenzylaminomethyl) epoxide (13) was used as common building block. The key step involved oxirane ring opening of 13 by the nucleophilic lithium aza‐enolate of hydrazones 12a and 12b. Subsequent hydrazone hydrolysis and intramolecular reductive amination afforded the alkaloid (+)‐deoxocassine and a new C‐6 ethyl analogue of this substance in good yields. The total synthesis of (+)‐deoxocassine and its new C‐6 ethyl analogue is reported. The key step of this synthetic pathway involves C–C coupling between syn‐(2R,1′S)‐2‐(1‐dibenzylaminomethyl)epoxide and an aza‐enolate of a hydrazone intermediate. This protocol is suitable to synthesize other “all‐cis” 2‐methyl‐6‐substituted piperidine‐3‐ol alkaloids.