Efficient Palladium-Catalyzed Coupling of Baylis-Hillman Acetates with an Allylstannane

Abstract

Acetates of Baylis-Hillman adducts derived from ethyl acrylate, methyl vinyl ketone, and acrylonitrile were coupled with allyltributylstannane using Pd(PPh 3 ) 4 or Pd(dba) 2 as the catalyst at room temperature to afford the corresponding trisubstituted alka-1,5-dienes in good to high yields.The Baylis-Hillman reaction is an important carbon-carbon bond-forming reaction affording highly functionalized alkenes. 1 Baylis-Hillman adducts and their acetates are valuable synthetic intermediates for the synthesis of a variety of heterocycles. 2 They are also used as intermediates for the preparation of trisubstituted alkenes bearing various functional groups by nucleophilic substitution 3 or a cross-coupling reaction with organometallics 4-6 using palladium and rhodium as a catalyst or alkyl halides using zinc 7 and trialkylindium. 8 Organic compounds containing a terminal C=C bond moiety are important for the construction of target molecules, such as by metathesis. The allylation of Baylis-Hillman adducts and their acetates is one of the most important reactions for the preparation of the 1,5-diene system. Two methods for the allylation of Baylis-Hillman adducts or their acetates have been developed. 9 One is the zinc-mediated allylation of BaylisHillman acetates with excess allyl bromide and zinc and the other is the boron trifluoride-diethyl ether mediated allylation of Baylis-Hillman adducts at 0 °C. However, these two methods have their own disadvantages; limited scope and anhydrous conditions. Recently, palladium-catalyzed cross-coupling reactions have become one of the most powerful and reliable methods for C-C bond formation. 10 Among these, the Stille reaction has widely been applied in organic synthesis because of the availability and stability of organostannanes and their ample compatibility with most organic functional groups. 11 As a result of studies on palladium-catalyzed reactions of Baylis-Hillman adducts and their acetates, we report the cross-coupling reaction of Baylis-Hillman acetates 1 with allyltributylstannane using tetrakis(triphenylphosphine)palladium(0) [Pd(PPh 3 ) 4 ] or bis(dibenzylideneacetone)palladium(0) [Pd(dba) 2 ] as the catalyst at room temperature under argon to give the corresponding trisubstituted alkenes 2 bearing terminal C=C bonds in good to high yields (Scheme 1). Scheme 1The cross-coupling reaction of Baylis-Hillman acetate 1a with allyltributylstannane using the Pd(dba) 2 /Ph 3 P/LiCl system in N,N-dimethylformamide-water 12 gave the coupling product 2a after 19 hours at 80 °C in 87% isolated yield. Based on this result, systematic studies were conducted to optimize the conditions for the reaction of acetate 1a with allyltributylstannane by changing temperature, palladium catalyst, and solvent (CH 2 Cl 2 , H 2 O, DMF, THF, MeOH). We found that the optimum system is Pd(PPh 3 ) 4 in N,N-dimethylformamide at room temperature under an argon atmosphere. The acetate 1a reacted with allyltributylstannane in the presence of Pd(PPh 3 ) 4 (5 mol%) in N,N-dimethylformamide at room temp...