Catalytic asymmetric hydrogenation of indoles using a rhodium complex with a chiral bisphosphine ligand PhTRAP

Highly enantioselective hydrogenation of N-protected indoles was successfully developed by use of the rhodium catalyst generated in situ from [Rh(nbd)2]SbF6 and the chiral bisphosphine PhTRAP, which can form a trans-chelate complex with a transition metal atom. The PhTRAP–rhodium catalyst required a base (e.g., Cs2CO3) for the achievement of high enantioselectivity. Various 2-substituted N-acetylindoles were converted into the corresponding chiral indolines with up to 95% ee. The hydrogenations of 3-substituted N-tosylindoles yielded indolines possessing a stereogenic center at the 3-position with high enantiomeric excesses (up to 98% ee).

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide

(R)–N-Acetyl-2-butylindolineC14H19NOEe = 94%[α]D20=-94.0 (c 1.00, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: R

(S)-3-Methyl-N-(p-toluenesulfonyl)indolineC16H17NO2SEe = 98%[α]D20=+29.4 (c 1.06, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: S