Catalytic enantioselective C–H functionalization of indoles with α-diazopropionates using chiral dirhodium(II) carboxylates: asymmetric synthesis of the (+)-α-methyl-3-indolylacetic acid fragment of acremoauxin A

An enantioselective C–H functionalization of N-methoxymethyl (MOM)-protected 2,3-unsubstituted indoles with α-diazopropionates has been effected via catalysis by dirhodium(II) tetrakis[N-phthaloyl-(S)-triethylalaninate], Rh2((S)-PTTEA)4, providing α-methyl-3-indolylacetates in high yields and with enantioselectivities of up to 86% ee. The effectiveness of this protocol was demonstrated by the first catalytic asymmetric synthesis of the (+)-α-methyl-3-indolylacetic acid fragment of acremoauxin A, a potent plant-growth inhibitor. Furthermore, the Fujioka protocol using a combination of TMSOTf and 2,2′-bipyridyl was shown to be superior for the removal of the N-MOM group.

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(R)-2,4-Dimethyl-3-pentyl 2-(1-methoxymethyl-1H-indol-3-yl)propionateC20H29NO382% ee[α]D20=-20.3 (c 1.04, CHCl3)Source of chirality: enantioselective C–H functionalizationAbsolute configuration: (R)

(R)-2,4-Dimethyl-3-pentyl 2-(1H-indol-3-yl)propionateC18H25NO282% ee[α]D22=-40.4 (c 0.71, CHCl3)Source of chirality: enantioselective C–H functionalizationAbsolute configuration: (R)

(R)-2-(1H-Indol-3-yl)propane-1-olC11H13NO82% ee[α]D24=-23.3 (c 0.41, MeOH)Source of chirality: enantioselective C–H functionalizationAbsolute configuration: (R)

(S)-α-Methyl-3-indolylacetic acidC11H11NO283% ee[α]D25=+42.6 (c 0.12, CH2Cl2)Source of chirality: enantioselective C–H functionalizationAbsolute configuration: (S)