Photocycloaddition reactions regiochemistry

The intermediate 37 can be viewed as arising from interaction of the triplet excited state of the indole with the alkene partner so as to form the most stable triplet 1,4-biradical intermediate possible. Alternatively, 37 may arise from attack of the 2-position of the triplet-excited indole on the less-substituted, and hence less sterically hindered terminus of the alkene. Either way, the preferential formation of 37 means that with monosubstituted alkenes, the photocycloaddition reaction with AT-acylin-doles is regioselective, while with unsymmetrically 1,2-disubstituted alkenes the reaction will be nonregioselective, as was seen for the reaction between N-benzoylindole and methyl 3-methyl-2-butenoate shown in Scheme 19. Should it be desired, the opposite regiochemistry to that normally obtained with monosubstituted alkenes can be induced by tethering the alkene to the indole [52] the reaction of 1,2-disubstituted alkenes can be made regioselective in the same way [53]. Examples of this are shown in Schemes 20 and 21. 

A1 Qaradawi, S., Gilbert, A., and Jones, D. T., Factors influencing the reaction-mode selectivity and regiochemistry of intermolecular photocycloaddition reactions of ethenes to polysubstituted benzenes. Reel. Trav. Chim. Pays-Bas, 114, 485,1995. 

To clarify the effects of linking chains, Gilbert et al. investigated the photocycloaddition of 163-180, which produce various types of adducts [231,234-237] (Scheme 53). In some cases, not only the meta addition but also ortho and para addition and ene reaction took place. The observed regiochemistry was rationalized in terms of the stabilization of zwitterionic intermediates and the steric constraints. 

The presence of both electron-donor (alkoxy) and electron-acceptor (cyano or carbomethoxy) substituents at the 2- and 3-positions respectively of the pyridine ring, have unlocked its photocycloaddition chemistry, and in recent years several such reactions of these heteroarenes have been described. Previously reported additions of ethenes involved acrylonitrile derivatives, but similar processes are now described with vinyl ethers as the addend. In these systems, however, it seems that the regiochemistry of addition is very sensitive to steric influences. Thus, although the dihydroazocine (48) is formed selectively from the 3-cyano-... 

He found that this is also true in the [2 + 2] photocycloaddition between 1,1-disubstituted silyl enol ethers (e.g., 75a) [83a] and benzaldehyde, as in Scheme 43. The regiochemistry is largely determined on the basis of the most stable biradical, which, before closing, arranges itself so that the bulkiest substituents are trans to each other. Hence, in the cases of 1,1-disubstituted and trisubstituted silyl enol ethers, sterics is the determining factor in the stereoselectivity of the Patem6-Buchi reaction. 

---