Transition-metal-catalyzed asymmetric allylic substitution is a useful reaction in organic synthesis. [1] In the reaction with symmetric C nucleophiles such as dialkyl malonates, good yields and high enantioselectivities can now be obtained with an appropriate combination of a transition metal and a chiral ligand. [2][3][4][5] In contrast to the symmetric C nucleophiles, allylic substitution of 3-substituted allylic alcohols B with unsymmetrical C nucleophiles A is a tough and challenging task, because regio-, diastereo-, and enantioselectivities must be controlled (Scheme 1). In the last few years, research has focused on finding catalysts and chiral ligands that favor the formation of branched chiral products D and E in the allylic substitution of a-amino esters A with B.[ 6, 7] We have already reported Pd-mediated asymmetric allylic alkylation of diphenylimino glycinate 1 with several allylic acetates in the presence of the chiral phase-transfer catalyst (PTC) 6 to give the chiral products C with high enantioselectivity (up to 97 % ee).[6a] In contrast to the palladium catalyst, some transition metals, such as Ir, [3] Mo, [4] and W, [5] promote allylic alkylation at the more highly substituted terminus of the allylic substrate. Trost et al. recently reported that Mocatalyzed asymmetric allylic alkylation with azlactones occurs at the more substituted terminus with high regio-, diastereo-, and enantioselectivity.[8] However, there are no reports concerning the asymmetric synthesis of both diastereomers D and E as major products from the same starting materials and the same chiral ligand. We report here the first enantioselective allylic substitutions of 1 catalyzed by an iridium complex of chiral phosphite 10, and the diastereoselective synthesis of the products 4 and 5 by simply switching the base employed (Scheme 2).Our previous work prompted us to examine PTC 6 as a chiral catalyst in Ir-catalyzed allylic substitutions (Table 1). We first carried out the Ir-catalyzed reaction of 1 and benzoate 2 a in the presence of the chiral PTC 6, 50% KOH, [{IrCl(cod)} 2 ] (cod = cyclooctadiene), and (PhO) 3 P (entry 1). The reaction was complete after 8 h at room temperature and gave the branched products 4 a and 5 a as major products (40 % yield, 4 a:5 a = 75:25) but with low enantioselectivity (46 % ee). We next examined the effect of chiral ligands 7-10[9] in place of chiral PTC 6 on the enantioselectivity. The reaction of 1 with 2 a was carried out in the presence of 50 % KOH (3 equiv), [{IrCl(cod)} 2 ] (10 mol %), and chiral phosphites (20-40 mol %). In all cases, no linear product could be detected. Indeed, the Scheme 1. Transition-metal-mediated asymmetric allylic substitution.Scheme 2. Ir-catalyzed asymmetric allylic substitution of 1 with 2 a, a'. Table 1: Ir-catalyzed asymmetric allylic substitution of 1 and 2 a, a' with chiral PTC 6 or various chiral ligands 7-10. [c]

[reaction: see text]. A chiral phase-transfer catalyst has been applied to the asymmetric allylation of the tert-butyl glycinate-benzophenone Schiff base with various allylic acetates for the first time to give the allylated products in good yields and with comparable to higher enantioselectivity than for asymmetric alkylation at the same temperature (91-96% ee) without any chiral ligands for coordinating to the palladium.

Pd-catalyzed asymmetric allylic alkylation of the glycine imino ester 1a has been developed using a chiral quaternary ammonium salt 3d without chiral phosphine ligands. The proper choice of the achiral Pd ligand, P(OPh)3, is important to achieve high enantioselectivity. By this method with the dual catalysts, numerous enantiomerically enriched alpha-allylic amino acids 4a-h could be prepared with comparable to higher enantioselectivity than that of the conventional asymmetric alkylation of 1a. In addition, the Pd-catalyzed reaction of 1a with 1-phenyl-2-propenyl acetate 2i afforded the branch product 6 with high enantio- and diastereoselectivity (>95% de, 85% ee).

The asymmetric synthesis of beta-substituted alpha-amino acids with use of iridium-catalyzed allylic substitution was described. The Ir-catalyzed allylic substitution of diphenylimino glycinate with allylic phosphates proceeded smoothly even at 0 degrees C and gave branch products with high enantioselectivity (up to 97% ee), when chiral bidentate phosphite bearing the 2-ethylthioethyl group was employed. In addition, both diastereomers of the branch products were synthesized stereoselectively by simply switching the base employed. These methods were also applied to the asymmetric synthesis of quaternary alpha-amino acids.