Enantioselective Synthesis of <i>cis</i>- and <i>trans</i>-2(<i>S</i>)-Amino-1-<i>d</i>-indane:  Debrominative [1,2]-Hydride Shift Rearrangement by Reduction of <i>cis</i>-2-Azido-1-bromoindane with LiAlD₄

Abstract

This article describes the synthesis of the racemic and optically pure forms of (1 R,2 S )- cis - and (1 S,2 S )- trans -2-Amino-1- d -indanes 2 {94% ee} and 3 {83% ee} (ee determined by 2 H NMR in chiral liquid crystal PBLG/CH 2 Cl 2, Courtieu, J. et al. J. Am. Chem. Soc. 1995, 117, 6520) prepared by LiAlD 4 reduction of (±)- and (1 S,2 S )- trans -2-azido-1-bromomoindane ( 11 ) {87% ee} and (±) and (1 R,2 S )- cis -2-azido-1-[(methanesulfonyl)oxy]indane ( 10 ) {83% ee}, respectively. Whereas the LiAlD 4 reduction of trans -2-azido-1-bromomoindane ( 11 ) led to cis -2-amino-1- d -indane 2 by a S N 2 pathway, exclusively, the reduction of cis -1-bromo derivative 12 gave only small amounts of the S N 2 product trans -2-amino-1- d -indane ( 3 ) (15%) accompanied by 2-amino-2- d -indane ( 4 ) (85%) in which the deuterium atom is incorporated in α position to the amino group. It was established that the primary amine 4 comes from a stereospecific [1,2]-hydride shift rearrangement. We propose that the azido group is reduced first, and the [1,2]-hydride shift rearrangement prevails over the competitive S N 2 substitution. The exclusive formation of trans -2-amino-1- d -indane ( 3 ) requires cis -2-azido-1-[(methanesulfonyl)oxy]indane ( 10 ) where the mesylate assisted by electrophilic Li + cation switches the deuteride attack to the ester carbon and the direct S N 2 substitution occurs before the azide is reduced.