1- Substituted 2-propenyl acetate, allylic alkylations

Phosphinous amides, based on proline and tetrahydroisoquinoline carboxylic acid, bearing a second donor center (50, Ar=Ph R =H, CH3,Tr, Ph R =H, CH3,Tr, Ph and 51, R =H,Tr R =H,Tr) (Scheme 40) have been developed for use in allylic alkylation and amination of substituted propenyl acetates, yielding the corresponding products in 87-98% (5-94% ee) and 29-97% (14-93% ee) respectively [55, 167]. With bidentate ligands of type 38 where R=(S)-PhMeCH, and with the bis(aminophosphanes) 52 (R=Ph) similar allylic alkylations have been also tested [168,169]. 

Thanks to the fundamental studies of Tsuji, Trost, and others, palladium-catalyzed allylic substitution has become a versatile, widely used process in organic synthesis [40]. The search for efficient enantioselective catalysts for this class of reactions is an important goal of current research in this field [41]. It has been shown that chiral phosphine ligands can induce substantial enantiomeric excesses in Pd-catalyzed reactions of racemic or achiral allylic substrates with nucleophiles [42]. Recently, promising results have also been obtained with chiral bidentate nitrogen ligands [43]. We have found that palladium complexes of neutral aza-semicorrin or methylene-bis(oxazoline) ligands are effective catalysts for the enantioselective allylic alkylation of l,3-diphenyl-2-propenyl acetate or related substrates with dimethyl malonate (Schemes 18 [25,30] and 19 [44]). 

Palladium(II)-allyl complexes with these ligands were found to be effective catalysts for allylic alkylations with stabilized carbanions. Under standard conditions, using 2 mol% of catalyst and a mixture of BSA and catalytic amounts of KOAc as base, racemic l,3-diphenyl-2-propenyl acetate smoothly reacted with dimethyl malonate or acetylacetone to afford optically active substitution products (Table 1). The phosphinophenyl-oxazoline with a phenyl group at the stereogenic center proved to be the optimal ligand for this substrate. After a remarkably short reaction time, the desired substitution products were isolated in essentially quantitative yields with enantiomeric excess of 97-99%. These values exceed the selectivities previously obtained with other ligands [41-43]. 

An interesting regiochemistry has been observed in the palladium-catalyzed allylic alkylation of ( )-3-substituted-2-propene acetate and 1-substituted 2-propenyl acetate. In this allylic substitution catalyzed by a palladium complex prepared from 1 in the presence of (/ )-MeO-MOP catalyst (P/Pd = 2/1), a selective substitution at the position originally substituted with acetate was observed (eq 62). Studies with 3-deuterio-2-cyclohexenyl acetate revealed that neutral phosphane Pd-complex is formed during the process. 

A highly enantioselective allylic alkylation occurs when l,3-diaryl-2-propenyl acetate reacts with differently substituted pyrroles and 4,7-dihydroindoles in the presence of a [Pd(C3H5)Cl]2-chiral alkene-phosphine ligand catalyst. Yields range from 64 to 97% with 81-97% ee. 

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