Catalytic enantioselective Michael addition reactions of α-nitroesters to α,β-unsaturated ketones

Abstract

Enantioselective Michael additions of α-nitroesters 2a-d with α,β-unsaturated ketones were carried out in the presence of a catalytic amount of chiral Al-Li-(R,R′)-2,2′-dihydroxy-1,1′-binaphthyl (‘AlLiBINOL’) complex prepared in situ from LiAlH 4 and 2.45 equiv. of (R,R′)-BINOL. The enantioselectivity of the Michael addition proved to be extremely temperature dependent: Michael adduct 4a showed 7% e.e when the reaction was performed at RT, whereas 72% e.e. of the opposite enantiomer of 4a was found when the 1,4-addition was performed at −23°C. Solvent variation showed that tetrahydrofuran gave the highest selectivity (up to 80% e.e.), whereas the highest enantioselectivity for the opposite enantiomer was found in methylene chloride (up to 25%). X-Ray structure analysis of the AlLi 3BINOL 3 complex 6 in combination with 27Al NMR studies showed that ‘AlLiBINOL’ is a mixture of aluminium complexes in solution.