Synthesis and application of P,olefin type axially chiral ligands with sec-alkyl groups

Abstract

Palladium-catalyzed asymmetric allylic substitution with indoles using a chiral ligand 3b, which have fewer hindered substituents such as secondary alkyl groups than 1-adamantyl group, gave desired products (R)-9 with high enantioselectivities (up to 96% ee).

Chiral P,Olefin Ligands with Rotamers for Palladium-Catalyzed Asymmetric Allylic Substitution Reactions

“…When the reaction was carried out with 1,3-diphenylprop-2-enyl pivalate instead of the acetate, product (R)-11a was obtained at a similar level of enantioselectivity (98% ee; entry 13). Table 3 Palladium-Catalyzed Asymmetric Allylic Alkylation of Indoles in the Presence of (S)-6a a According to the observed stereochemical outcome as well as our previous relevant reports, 4,5 we propose a possible pathway for product formation (Scheme 4). We recently reported that the chiral ligands (aR)-1 with C(aryl)-N(amine) bond axial chirality gave (S)-products 10 in a Pdcatalyzed asymmetric allylic substitution reactions with malonates.…”

“…We also synthesized the aminophosphine 3, which has a lesshindered substituent, in this case a cyclohexyl group; this compound did not display axial chirality of the C(aryl)-N(amine) bond. 5 We also reported that analogues of aminophosphine (aR)-1c without an internal olefin group, such as the aminophosphine (aR)-4, were ineffective as chiral ligands in a Pd-catalyzed asymmetric allylic substitution reaction. 4a…”

“…2,3 We recently reported the synthesis of phosphine-olefin-type chiral ligands (aR)-1 and (aR)-2 with C(aryl)-N(amine) bond axial chirality (Figure 1). 4,5 In these ligands, one substituent of the nitrogen atom at the axially chiral C(aryl)-N(amine) bond was a bulky alkyl group, such as a 1-or 2-adamantyl group. We also synthesized the aminophosphine 3, which has a lesshindered substituent, in this case a cyclohexyl group; this compound did not display axial chirality of the C(aryl)-N(amine) bond.…”

Recent Advances in Enantioselective Pd-Catalyzed Allylic Substitution: From Design to Applications

“…One of these modified ligands, the N -1-adamantyl- N -cinnamylaniline derivative L106 was found to induce high enantioselectivities in the allylic alkylation of rac -1,3-diarylallyl acetates with a range of indoles ( Scheme 91 ). 328 …”

“…Pd-Catalyzed Allylic Substitution of 1,3-Diarylallyl Acetates with a Range of (a) Indoles and (b) Hydrazones Using Pd/L100 as Catalyst was found to induce high enantioselectivities in the allylic alkylation of rac-1,3-diarylallyl acetates with a range of indoles (Scheme 91). 328 Yamamoto and co-workers developed a helicene-derived phosphine-olefin ligand L107 324 that exerted efficient enantiocontrol (ee values up to >99%) in the allylic alkylation of rac-1,3-diphenylallyl acetate with dimethyl malonate, indoles and alkyl alcohols (Scheme 92).…”