Design, synthesis and application of a new type of bifunctional Le-Phos in highly enantioselective γ-addition reactions of N-centered nucleophiles to allenoates

A novel class of bifunctional cyclic phosphine catalysts (Le-Phos) is reported, which showed good performances in enantioselective γ-addition reactions of N-centered nucleophiles and allenoates under mild conditions.


Synthesis and general data of catalysts (SP, R, S, RS)-L3
The general procedure was followed by using (SP, R, S, RS)-L3 borane complex (545 mg, 0.90 mmol) and Et2NH (2.0 mL). The resulting solution was stirred at 50 ℃ for 5 hours and then concentrated under vacuum. The residue was purified by silica gel flash chromatography (25% EtOAc in PE) to afford (SP, R, S, RS)-L3 as a white solid (426 mg, 80%).

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The general procedure was followed by using (RP, S, S, RS)-L4 borane complex (629 mg, 1.05 mmol) and Et2NH (2.0 mL). The resulting solution was stirred at 50 ℃ for 5 hours and then concentrated under vacuum. The residue was purified by silica gel flash chromatography (20% EtOAc in PE) to afford (RP, S, S, RS)-L4 as a white solid (492 mg, 80%).

Synthesis and general data of catalysts (RP, S, S, RS)-L5
The general procedure was followed by using (RP, S, S, RS)-L5 borane complex (

General procedure for the cascade reaction of 2-oxazolidones:
To a flame-dried glass tube with a magnetic stirring bar were added 2-oxazolidone 1a (8.7 mg, 0.10 mmol) and (SP, R, S, RS)-L4 (5.9 mg, 0.01 mmol), followed by the addition of dry 1,2-Dichloroethane (1.5 mL). [5] Then the allenoate 2a (28.0 mg, 0.20 mmol) was slowly added via syringe at room temperature under inert atmosphere. The reaction mixture was stirred for 24 h, and TLC show that the rection was completed.
The general procedure was followed using 1a (
The general procedure was followed using 1a (
The general procedure was followed using 1a (
The general procedure was followed using 1a (
The general procedure was followed using 1c (

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The general procedure was followed using 1d (

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The general procedure was followed using 1g (
The general procedure was followed using 1g (
The general procedure was followed using 1g (
The general procedure was followed using 4a (0.1 mmol) and 5n (

General procedure for variation of TsNH2 components.
To a flame-dried glass tube with a magnetic stirring bar were added TsNH2 (17.1 mg, 0.10 mmol) and (SP, R, S, RS)-L5 (7.4 mg, 0.02 mmol), followed by the addition of dry Et2O (1.5 mL). [5] Then the allenoate 2o (25.2 mg, 0.20 mmol) was slowly added via syringe at room temperature under inert atmosphere. The reaction mixture was stirred for 48 h, and TLC show that the rection was completed. Then Et2O was removed under reduced pressure. The residue was purified by column chromatography on silica gel (petroleum ether/ethyl acetate = 2:1) to afford 7ao (17.2 mg, 58% yield).