The stereochemistry of the SN2' reaction

The synthesis of (S)-(+)-3-chloro-1-butene-(Z)-1-d from 3-butyn-2-one was performed. The optically active, deuterium-labeled allylic chloride was then used as the substrate in a study of the stereochemistry of the S_N2' reaction with trimethylamine.

The synthesis was achieved by effecting an asymmetric reduction of 3-butyn-2-one with Alpine-Borane, reduction of the carbon-carbon triple bond with lithium aluminum hydride and quenching with D₂O, and conversion into the chloride by reaction with triphenylphosphine in hexachloroacetone.

Reaction of (S)-(+)-3-chloro-1-butene-(Z)-1-d with trimethylamine produced a mixture of three products: S_N2 product, cis-S_N2' product, and trans-S_N2' product. This mixture of unsaturated ammonium salts was reduced with diimide and dealkylated by refluxing with diazabicyclo[2.2.2]octane. Separation of the S_N2- and S_N2'-derived saturated ammonium salts, or of the corresponding amines was not possible.

Polarimetric measurements were obtained on the mixture of amines after reduction and dealkylation of the ammonium salts. An attempt was made to relate the readings observed to the maximum specific rotations of N,N-dimethyl-1-butanamine-1-d and N,N-dimethyl-2-butanamine. Such a relationship would have made a determination of the stereochemistry of the S_N2' process possible. Calculations based on various assumptions indicated that such a relationship was not obvious in the present case. No quantitative conclusion concerning the stereochemistry of the S_N2' reaction in question was possible, but the sign of rotation of the amine mixture indicated that it was, in all likelihood, syn.