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Lewis Base Effects in the Baylis−Hillman Reaction of Arenecarbaldehydes and N ‐Arylidene‐4‐methylbenzenesulfonamides with α,β‐Unsaturated Cyclic Ketones
Author(s) -
Shi Min,
Xu YongMei,
Zhao GuiLing,
Wu XiaoFeng
Publication year - 2002
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/1099-0690(200211)2002:21<3666::aid-ejoc3666>3.0.co;2-9
Subject(s) - chemistry , lewis acids and bases , base (topology) , baylis–hillman reaction , organic chemistry , medicinal chemistry , stereochemistry , adduct , catalysis , mathematical analysis , mathematics
In investigations into the Baylis−Hillman reaction between arenecarbaldehydes and 2‐cyclohexen‐1‐one or 2‐cyclopenten‐1‐one, we found that the 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 abnormal 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 in good or excellent yields. Moreover, application 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 PBu 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 formed 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 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‐unsaturated cyclic ketone substrates were also examined. (© Wiley‐VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)