Lewis Base Effects in the Baylis−Hillman Reaction of Arenecarbaldehydes and N-Arylidene-4-methylbenzenesulfonamides with α,β-Unsaturated Cyclic Ketones

Abstract

In investigations into the Baylis-Hillman reaction between arenecarbaldehydes and 2-cyclohexen-1-one or 2-cyclopenten-1-one, we found that te reaction is very complicated, because the Lewis bases, solvents, the substrates, and the ring-size of the α,β-unsaturated cyclic ketone can all significantly affect the Baylis-Hillman reaction rate and even the reaction product, In particular, the abnomal adducts 3 were formed along with the normal Baylis-Hillman adducts 2 on treatment of arenecarbaldehydes and 2-cyclopenten-1-one under Baylis-Hillman reaction conditions in the presence of Pbu^3 as a Lewis base. On the other hand, in Baylis-Hillman reactions between N-benzylidene-4-methylbenzenesulfonamides and 2-cyclohexen-1-one or 2-cyclopenten-1-one, we found that the reaction could be greatly accelerated in the presence of catalytic amounts of DMAP to give the normal Baylis-Hillman adducts 4 or 6 ingood or excellent yields. Moreover, appliation of Baylis-Hillman reaction conditions to N-arylidene-4-methylbenzenesulfonamide and 2-cyclopenten-1-one in the presence of Pbu^3 as a Lewis base provided the normal Baylis-Hillman adducts 6 in very high yields within 5 h. In the presence of Puu^3 or DBU as a Lewis base for reactions between N-arylidene-4-methylbenzenesulfonamides and 2-cyclohexen-1-one, however, the abnormal Baylis-Hillman adducts 3-aryl-2-(4-tolylsulfonyl)-2-azabicyclo[2.2.2]octan-5-ones 5 were fromed at the same time. In addition, in reactions between N-arylidene-4-methylbenzenesulfonamides and 2-cyclohepten-1-one or 2-cycloocten-1-one, the reactions were very sluggish in the presence of a range of Lewis bases, and the abnormal Baylis-Hillman adducts 7 or 9-derived from aldol condensations-were obtained in moderate yields together with the normal Baylis-Hillman adducts 7 or 9-derved from aldol condensations-were obtained in moderate yields together with the normal Baylis-Hillman adduct 4. When Baylis-Hillman reaction conditions were applied to N-arylidene-4-methylbenzenesulfonamides and 2-cycloocten -1- one in methanol, products 10 - derived from Michael additions of methanol to 9-were formed as the major products, along with traces of 9. In general, the ring-size of the α,β-unsaturated cyclic ketone can significantly affect the reaction products and rates, the Baylis-Hillman reaction and the aldol condensation reaction taking place at the same time for 2-cyclohexen-1-one or 2-cyclohepten-1-one. For large-sized α,β-unsaturated cyclic ketones such as 2-cycloocten-1-one, only aldol condensation reactions occurred. The substituent effects in all α,β-bunsaturated cyclic ketone substrates were also examined.