Asymmetric Cu-catalyzed Henry reaction promoted by chiral camphor-derived β-amino alcohols with a thiophene moiety

Four chiral amino alcohols with a sulfur substituent were synthesized from d-(+)-camphor and utilized as ligands in Cu(I)-catalyzed asymmetric Henry reactions between nitromethane and various aldehydes. The reactions were carried out under mild conditions with excellent enantioselectivities and good yields without the exclusion of air or moisture. The highest enantioselectivity was observed (up to 96% ee) with ligand 3c in CH3NO2 at 0 °C.

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(1R,2S,3R,4S)-1,7,7,Trimethyl-3-(2-(4-tolythio)benzylamino)bicycle-[2,2,1]heptan-2-olC24H31NOSAbsolute configuration: (1R,2S,3R,4S)[α]D22 = +35.1 (c 0.77, CHCl3)Source of chirality: (1R,2S,3R,4S)-3-Amino-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol

(1R,2S,3R,4S)-1,7,7,Trimethyl-3-((thiophen-2-yl)methylamino)bicycle[2,2,1]heptan-2-olC15H23NOSAbsolute configuration: (1R,2S,3R,4S)[α]D22 = +36.4 (c 0.67, CHCl3)Source of chirality: (1R,2S,3R,4S)-3-Amino-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol

(1R,2S,3R,4S)-1,7,7,Trimethyl-3-((5-Methylthiophen-2-yl)-methylamino)bicycle[2,2,1]heptan-2-olC16H25NOSAbsolute configuration: (1R,2S,3R,4S)[α]D22 = +38.6 (c 0.83, CHCl3)Source of chirality: (1R,2S,3R,4S)-3-Amino-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol

(1R,2S,3R,4S)-1,7,7,Trimethyl-3-(Furan-2-ylamino)bicycle[2,2,1]-heptan-2-olC15H23NO2Absolute configuration: (1R,2S,3R,4S)[α]D22 = +44.3 (c 0.40, CHCl3)Source of chirality: (1R,2S,3R,4S)-3-Amino-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol