Bulky Monodentate Phosphoramidites in Palladium‐Catalyzed Allylic Alkylation Reactions: Aspects of Regioselectivity and Enantioselectivity

Abstract

A series of bulky monodentate phosphoramidite ligands, based on biphenol, BINOL and TADDOL backbones, have been employed in the Pd‐catalysed allylic alkylation reaction. Reaction of disodium diethyl 2‐methyl malonate with monosubstituted allylic substrates in the presence of palladium complexes of the phosphoramidite ligands proceeds smoothly at room temperature. The regioselectivities observed depend strongly on the leaving group and the geometry of the allylic starting compounds. Mono‐coordination occurs when these ligands are ligated in [Pd(allyl)(X)] complexes (allyl=C3H5, 1‐CH3C3H4, 1‐C6H5C3H4, 1,3‐(C6H5)2C3H3; X=Cl, OAc). The solid‐state structure determined by X‐ray diffraction of [Pd(C3H5)(1)(Cl)] reveals a non‐symmetric coordination of the allyl moiety, caused by the stronger trans influence of the phosphoramidite ligand relative to X−. In all of these complexes, the syn,trans isomer is the major species present in solution. Because of fast isomerisation and high reactivity of the syn,cis complex, the major product formed upon alkylation is the linear product, especially for monosubstituted phenylallyl substrates in the presence of halide counterions. In the case of biphenol‐ and BINOL‐based phosphoramidites, however, a strong memory effect is observed when 1‐phenyl‐2‐propenyl acetate is employed as the substrate. In this case, nucleophilic attack competes effectively with the isomerisation of the transient cinnamylpalladium complexes. The asymmetric allylic alkylation of 1,3‐diphenyl‐2‐propenyl acetate afforded the chiral product in up to 93 % ee. Substrates with smaller substituents gave lower enantioselectivities. The observed stereoselectivity is explained in terms of a preferential rotation mechanism, in which the product is formed by attack on one of the isomers of the intermediate [Pd{1,3‐(C6H5)2C3H3}(L)(OAc)] complex.

Better Performance of Monodentate P‐Stereogenic Phosphanes Compared to Bidentate Analogues in Pd‐Catalyzed Asymmetric Allylic Alkylations

“…A similar range of selectivity was observed when bulky monodentate phosphoramidites were used. [19] When the cationic precursor species were obtained from [PdCl(η 3 -2-Me-C 3 H 4 ), a], where the ratio Pd/P was 1:1, the reaction was slower (entries 1, 2, 7, 8) but the regioselectivity was similar. The use of the neutral complexes (Pd/P = 1:1) as precursors led to the same regioselectivity as that observed for the cationic complexes 3 (Pd/P = 1:2).…”

“…For example, some monodentate phosphoramidites show over 90 % ee in the allylic alkylation of 1,3-diphenylallyl acetate. [19] In the regioselectivity for asymmetric substrates like (E)-3- Table 1. Asymmetric allylic alkylation of rac-3-acetoxy-1,3-diphenyl-1-propene with dimethyl malonate catalyzed by Pd/Pstereogenic phosphane complexes.…”

Nonlinear Effects in Asymmetric Catalysis

“…(38); BSA = N,O-bis(trimethylsilyl)acetamide]. [115] The involvement of only one 142 a ligand in the catalytically active Pd species [Pd(C 3 H 5 )(142 a)(OAc)] was suggested.…”

Palladium-catalyzed desulfinylative C–C allylation of Grignard reagents and enolates using allylsulfonyl chlorides and esters

“…In the case of Pd(PPh 3 ) 4 -catalyzed reactions it seems that the (crotyl)Pd(ligand) intermediate does not make any great difference for the Nu insertion into the non-substituted (less steric hindrance) and the methyl substituted center of the (allyl)palladium moiety. For more than 30 years it has been known that the regioselectivity of allylic alkylation, [86][87][88][89][90][91][92][93][94][95] allylic vinylation, [96][97][98] and allylic arylation [99][100][101][102] depends on the nature of the catalyst. Although many more experiments should be carried out to approach a mechanistic interpretation of our results, we propose at this stage that (allyl)palladium intermediates 7 and 8 are formed by reactions of 2c or 2d with PdCl 2 (PhCN) 2 and Pd(PPh 3 ) 4 , respectively (Scheme 3).…”