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Ni-Catalyzed Enantioselective Benzylation of Secondary Phosphine Oxide

Wen-Qiang Cai, Qi Wei and Qing-Wei Zhang*

*Department of Chemistry, University of Science and Technology of China, Hefei 230026, China, Email: qingweizustc.edu.cn

W.-Q. Cai, Q. Wei, Q.-W. Zhang, Org. Lett., 2022, 24, 1258-1262.

DOI: 10.1021/acs.orglett.2c00209



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Abstract

A nickel-catalyzed benzylic substitution of secondary phosphine oxide provides dialkylated P-stereogenic tertiary phosphine oxides with high enantioselectivities. The reaction was performed under mild conditions with commercially available benzyl chlorides and bench stable secondary phosphine oxides, exhibiting broad functional group tolerance.

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proposed mechanism



Enantioselective benzylic alkylation of secondary phosphine oxide

To a 4 mL vial containing a magnetic stirring bar was added Ni(cod)2 (2.8 mg, 10 mol%) and (S,S)-Me-Duphos (3.3 mg, 11 mol%) in mesitylene (2 mL), the mixture was stirred at r.t. for 10 minutes. then i-PrOH (5.0 equiv, 38.2 μL), K2HPO4 (43.5 mg, 2.5 equiv.) (or K2CO3 (34.5 mg, 2.5 equiv.) as noted), benzyl chloride (0.1 mmol, 1.0 equiv.) and secondary phosphine oxide (0.2 mmol, 2.0 equiv.) were added subsequently, the vial was capped and taken out of glovebox. The reaction was kept stirring at r.t. for 6 days, then the reaction mixture was filtered through a short pad of silica gel. The filtrate was concentrated at reduced pressure and purified by flash column chromatography to afford the desired product.


Key Words

phosphine oxides


ID: J54-Y2022