pi-Facial selectivities and proximal/distal regioselectivities in Diels-Alder reactions of unsymmetrical, cage-annulated 1,3-cyclohexadienes

Diels-Alder cycloaddition of hexacyclo[7.5.1.0(1.6).0(6.13).0(8.12).0(10.14 )]pentadeca-2,4-diene-7,15-dione (1) to ethyl propiolate proceeds with pi - facial selectivity to afford two cycloadducts, 4b and 5b (product ratio: 4b /5b=80:20). Thermal [4+2] cycloaddition of hexacyclo[7.5.2.0(1.6).0(6.13).0 (8,12).0(10.14)]hexadeca-2,4-diene-7,16-dione (2) to ethyl propiolate affor ds two isomeric cycloadducts, i.e. 6c and 6d (product ratio: 6c/6d=40:60). Cycloadducts 6c and 6d are formed with a high degree of endo pi -facial sel ectivity but with only modest proximal/distal regioselectivity. The corresp onding [4+2] cycloaddition of 2 (diene) to dimethyl acetylenedicarboxylate (dienophile) produced a single cycloadduct, 7b. These observations have bee n further examined by employing Hartree-Fock relative energies of transitio n states presumably formed enroute to the various products. Interestingly, filled orbital electrostatic repulsion between the incoming dienophile and the C=O groups in the diene substrate does not appear to be a significant f actor that might influence pi -facial selection in this [4+2] cycloaddition . Finally, thermal [4+2] cycloaddition of cyclopentadiene (diene) to dienop hile 3 proceeded with a high degree of pi -facial selectivity to afford a s ingle cycloadduct, 9b. (C) 2001 Elsevier Science Ltd. All rights reserved.