Recently, we reported an efficient palladium(0) catalyzed allylation of a non-stabilized nucleophile, lithium enolate of ethyl isobutyrate 2a, with monoepoxide of isoprene la, as a first step in the total synthesis of epiilludol (scheme 1).] The synthetic value of the regio-and stereoselective allylic alkylation of vinyloxiranes with nucleophiles such as malonates, 13-diketones, [~-ketoacids or 13-ketosulfones in the presence of palladium( 0) catalysts is well documented. 2 It takes place at the distal position of the hydroxyl function and forms the E-allylic alcohol as major stereoisomer. Neutral conditions are generally used because the in situ generated alcoholate is enough basic to deprotonate the pronucleophilic entity. EtO2C,,./R5 R4 /~-'* R1 1.1"/* PtI(OAc)2,2.5*/.clppe, RR4~R~3 THF, r.t. ,.
R1
la-e 2a-c 3-12 scheme 1
Only a few examples describe the addition of non-stabilized nucleophiles to r~-allylpalladium complexes) 2b Specially starting from vinyloxiranes, Trost noticed that a simple ketone, cyclopentanone, could participate in this type of allylation albeit in modest yield (29%), as well as Tsuji who described without details the same reaction from cyclohexanone silylenol ether. 4 On another hand, an allylic monosulfone was employed as a nucleophile in the indolizidine allo-pumiliotoxine 339B synthesis. 5 An alternative to reach the allylic alkylation of 1,3-dienes monoepoxides with simple ketone enolates is produced by the use of [3-ketoacids as nucleophiles