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 (1R,2S)-cis- and (1S,2S)-trans-2-Amino-1-d-indanes 2 {94% ee} and 3 {83% ee} (ee determined by 2H NMR in chiral liquid crystal PBLG/CH2Cl2, Courtieu, J. et al. J. Am. Chem. Soc. 1995, 117, 6520) prepared by LiAlD4 reduction of (±)- and (1S,2S)-trans-2-azido-1-bromomoindane (11) {87% ee} and (±) and (1R,2S)-cis-2-azido-1-[(methanesulfonyl)oxy]indane (10) {83% ee}, respectively. Whereas the LiAlD4 reduction of trans-2-azido-1-bromomoindane (11) led to cis-2-amino-1-d-indane 2 by a SN2 pathway, exclusively, the reduction of cis-1-bromo derivative 12 gave only small amounts of the SN2 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 SN2 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 SN2 substitution occurs before the azide is reduced.