Diastereoselective protonation of extended pyrrol-3-en-2-one enolates: an attempted ‘de-epimerisation’

The extended cyclic enolate derived from a simple pyrrol-3-en-2-one (butenolactam) was deuterated at the 5-position with very high diastereoselectivity if the nitrogen atom carries an α-methyl-p-methoxybenzyl group. A similar diastereoselective protonation was observed in a pyrrol-3-en-2-one formed by dearomatising cyclisation of a pyrrole. Protonation of an N-α-methyl-p-methoxybenzyl dihydroisoindolone lacked stereoselectivity.

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(S)-N-[1-(4-Methoxyphenyl)ethyl]acrylamideC12H15NO2Ee = 100%[α]D22=-159.7 (c 0.12, CHCl3)Source of chirality: derivative of commercial compoundAbsolute configuration: (S)

(S)-N-Allyl-N-[1-(4-methoxyphenyl)ethyl]acrylamideC15H19NO2Ee = 100%[α]D22=-86.0 (c 0.02, CHCl3)Source of chirality: derivative of commercial compoundAbsolute configuration: (S)

(S)-1-[1-(4-Methoxyphenyl)ethyl]-1,5-dihydropyrrol-2-oneC13H15NO2Ee = 100%[α]D22=-122.0 (c 0.15, CHCl3)Source of chirality: derivative of commercial compoundAbsolute configuration: (S)

(S)-1-[1-(4-Methoxyphenyl)ethyl]-3-methyl-1,5-dihydropyrrol-2-oneC14H17NO2Ee = 100%[α]D22=-124.2 (c 0.15, CHCl3)Source of chirality: derivative of commercial compoundAbsolute configuration: (S)

(S)-1-[1-(4-Methoxyphenyl)ethyl]-3,3-dimethyl-1,3-dihydropyrrol-2-oneC15H19NO2Ee = 100%[α]D22=-126.4 (c 0.15, CHCl3)Source of chirality: derivative of commercial compoundAbsolute configuration: (S)

(S,S)-1-[1-(4-Methoxyphenyl)ethyl]-3,3-dimethyl-1,3-dihydropyrrol-2-oneC14H17NO2Ee = 100%[α]D22=-95.1 (c 0.10, CHCl3)Source of chirality: diastereoselective deuterationAbsolute configuration: (S,S)

(S,S)-2-[1-(4-Methoxyphenyl)ethyl]-3-phenyl-2,3-dihydroisoindol-1-oneC23H21NO2Ee = 100%[α]D22=-193.3 (c 0.10, CHCl3)Source of chirality: diastereoselective cyclisationAbsolute configuration: (S,S)

(S,R)-2-[1-(4-Methoxyphenyl)ethyl]-3-phenyl-2,3-dihydroisoindol-1-oneC23H21NO2Ee = 100%[α]D22=+171.9 (c 0.08, CHCl3)Source of chirality: diastereoselective cyclisationAbsolute configuration: (S,R)