Synthesis of chiral pentacyclo-undecane macrocycles and their use in enantioselective Michael addition reactions

The synthesis of a new class of chiral cage annulated macrocycles with five donor atoms and C-1 symmetry is reported. The ability of the chiral hosts to catalyse enantioselective Michael addition reactions were investigated. The cage annulated hosts catalysed the addition of 2-nitropropane to chalcone with high enantioselectivities (up to 92% ee) but with lower turnover rates than previously reported systems. Using sodium methoxide as a base resulted in a classical catalytic reaction for the addition of 2-nitropropane to chalcone. The reaction did not proceed in the absence of the macrocycle. The pentacyclo-undecane (PCU) hosts however, were unsuccessful in catalysing the addition of methyl phenylacetate to methyl acrylate. The structures and energies of the macrocycles with sodium methoxide were calculated using a high level density functional theory (DFT) calculation, which indicates that the complexes should be stable at room temperature. According to the DFT optimised complexes, it appears as if the PCU macrocycles are effectively shielding the base from sterically demanding reagents. (C) 2004 Elsevier Ltd. All rights reserved.