Intramolecular photochemical dioxenone-alkene [2+2] cycloadditions as an approach to the bicyclo[2.1.1]hexane moiety of solanoeclepin A

A synthesis of the bicyclo[2.1.1]hexane substructure of solanoeclepin A. (1 ), the most active natural hatching agent of potato cyst nematodes, was app roached via an intramolecular [2 + 2] photocycloaddition. Aldehyde 12 conta ining the dioxenone chromophore served as a useful starting material, allow ing the synthesis of a variety of photocycloaddition substrates via Grignar d addition or via a Nozaki-Hiyama-Kishi reaction. Photolysis of the unsubst ituted alkene 14 led to the expected crossed cycloadduct bicyclo[2.1.1]hexa ne 15 according to the so-called rule of five. However, several functionali zed alkenes 18, 20, and 31 exhibited a complete reversal of cycloaddition r egioselectivity, providing straight cycloadducts bicyclo[2.2.0]hexanes 21-2 6 and 4, respectively. Their structures were proved by a combination of ext ensive NMR measurements, X-ray analyses, and subsequent retro-aldol reactio ns. The latter de Mayo process allowed the formation of spiro[3.5]nonane 35 and spiro[3.4]octane 36 as well as the cyclobutanes 37 and 38. Finally, th e cyclization of the more rigid lactone precursor 28 occurred in high yield in the desired fashion with complete regio- and stereoselectivity to give 3 containing the core bicyclo[2.1. 1]hexane skeleton of the natural product .