Diastereoselective Pomeranz–Fritsch–Bobbitt synthesis of (S)-(−)-salsolidine using (R)-N-tert-butanesulfinylimine as a substrate

The highly diastereoselective addition of methyl Grignard reagent to chiral (R)-N-tert-butanesulfinylimine 8 was the key step in the synthesis of (S)-(−)-salsolidine 1 of high enantiomeric purity. The resulting addition product, tert-butanesulfinylamide 9, was then subjected to cyclization via amine 10 and Pomeranz–Fritsch aminoacetal 11.

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(RS)-(−)-N-(3,4-Dimethoxybenzylidene)-2-methylpropanesulfinamideC13H19NO3S[α]D = −19.1 (c 0.185, CH2Cl2)Source of chirality: N-tert-butanesulfinylamideAbsolute configuration: (RS)

(RS,S)-(−)-N-[1-(3,4-Dimethoxyphenylethyl)]-2-methylpropanesulfinamideC14H23NO3SDe 98% [by chiral HPLC analysis][α]D = −100.0 (c 1.105, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (RS,S)

(S)-(−)-1-(3,4-Dimethoxyphenyl)ethylamine hydrochlorideC10H15NO2·HCl[α]D = −6.9 (c 0.7, MeOH)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-(−)-N-(2,2-Diethoxyethyl)-1-(3,4-dimethoxyphenyl)ethylamineC16H27NO4[α]D = −29.6 (c 0.8, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)