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
see article for more reactions
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.
see article for more examples
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
ID: J54-Y2022