P d ( O A c ) 2 -M e d i a t e d O n e -P o t S y n t h e s i s o f T r i s u b s t i t u t e d A l k e n e s AAbstract: A simple and efficient stereoselective synthesis of Z-and E-isomers of trisubstituted alkenes has been developed by treating Baylis-Hillman (BH) acetates with palladium acetate and the stabilized ylide (ethoxycarbonylmethylene)triphenylphosphorane. Several ethyl acrylate and acrylonitrile-derived BH acetates were used as substrates, which yielded the corresponding trisubstituted alkenes stereoselectively in good yields.The Baylis-Hillman reaction, which involves the coupling of activated vinylic systems with electrophiles under the catalytic influence of a tertiary amine, gives rise to adducts with a new stereocenter (Baylis-Hillman adducts) and has proven to be a very useful carbon-carbon bond forming method in the synthesis of highly functionalized molecules. 2 These adducts have proved to be very useful multifunctional synthons for the preparation of trisubstituted alkenes, which have been widely found in various biologically active natural products such as pheromones and antibiotics. 3 The biological potential of these alkene moieties is largely dependent on their isomeric purity.In the past few years the scope of Baylis-Hillman chemistry has increased dramatically. 4 Basavaiah et al. reported on the Johnson-Claisen rearrangement of Baylis-Hillman adducts. 5 In a recent study, Narender et al. found that the BH adducts derived from substituted 2-chloronicotinaldehyde exhibited promising antimalarial activity against Plasmodium falsiparum. 6 Kim et al. have recently reported the synthesis of 5-arylpent-4-enoate derivatives by treating a BH acetate and a stabilized ylide to form a phosphonium salt followed by hydrolysis with aqueous KCN. They observed that ethyl acrylate derived adducts yielded stereoselectively the E-isomers whereas the acrylonitrile-derived adducts resulted in E/ Z-isomers. 7 It has been our long-standing endeavor to develop new methods to convert the BH adducts into highly functionalized trisubstituted alkenes efficiently with better stereoselectivity. 8 Herein we report the first, one-pot, Pd(OAc) 2 -mediated Michael addition of a stabilized ylide to BaylisHillman acetates to yield the corresponding trisubstituted alkene diesters with appreciable degrees of stereoselectivity.The Baylis-Hillman acetates 1-9 were prepared according to standard methods 2,5 by treating the aromatic aldehyde components with the corresponding ethyl acrylates/ acrylonitrile to give the corresponding adducts in good yields. The simple Baylis-Hillman acetate 1 derived from benzaldehyde and ethyl acrylate, when treated with (ethoxycarbonylmethylene)triphenylphophorane in the presence of palladium acetate (6 mol%) in benzene under reflux for 13 hours, afforded the Michael addition product, the alkene diester 1a, in good yield and with complete E-selectivity (Scheme 1).
Scheme 1When the Baylis-Hillman acetate derived from benzaldehyde and acrylonitrile was exposed to similar reaction conditions the...
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