First asymmetric aminohydroxylation of acrylamides

The first examples of the asymmetric aminohydroxylation of acryl amides are reported. This was accomplished with chiral acrylamides as substrates, which undergo diastereoselective oxidative transformation within the so-called ‘second catalytic cycle’ with diastereomeric excesses reaching 100:0. The reaction relies solely on the stereochemical information provided by the enantiomerically pure starting materials. A stereochemical model for the observed asymmetric induction is provided.

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(2R)-N-(S)-[1-(Methyloxycarbonyl)ethyl]-2-hydroxy-3-(tosylamino)propanamideC14H20N2O6SEe: 100%[α]D = +21 (c 1.0, methanol)Source of chirality: diastereoselective catalysis

(2R)-2-Hydroxy-N-((S)-1-phenylethyl)-3-(tosylamino)propanamideC18H22N2O4SEe: 100%[α]D = −50 (c 0.3, acetone)Source of chirality: diastereoselective catalysis

(2S)-2-Hydroxy-N-((R)-1-phenylethyl)-3-(tosylamino)propanamideC18H22N2O4SEe: 100%[α]D = +48 (c 0.26, acetone)Source of chirality: diastereoselective catalysis

(2R)-2-Hydroxy-N-[(S)-1-(2-naphthyl)ethyl]-3-(tosylamino)propanamideC22H24N2O4SEe: 100%[α]D = −122 (c 0.5, acetone)Source of chirality: diastereoselective catalysis

(2R)-2-Hydroxy-2-methyl-N-((S)-1-phenylethyl)-3-(tosylamino)propanamideC19H24N2O4SEe: 100%[α]D = −23 (c 0.4, acetone)Source of chirality: diastereoselective catalysis

(2S)-2-Hydroxy-2-methyl-N-((S)-1-phenylethyl)-3-(tosylamino)propanamideC19H24N2O4SEe: 100%[α]D = −64 (c 0.7, acetone)Source of chirality: diastereoselective catalysis

(2R,3R)-2-Hydroxy-N1,N4-bis((S)-1-phenylethyl)-3-(tosylamino)succinamideC27H31N3O5SEe:100%[α]D = −141 (c 0.23, MeOH)Source of chirality: diastereoselective catalysis

(2S,3S)-2-Hydroxy-N1,N4-bis((S)-1-phenylethyl)-3-(tosylamino)succinamideC27H31N3O5SEe: 100%[α]D = −78 (c 0.1, DMSO)Source of chirality: diastereoselective catalysis