TARTROL-derived chiral phosphine–phosphite ligands and their performance in enantioselective Cu-catalyzed 1,4-addition reactions

By using (R,R,R,R)-2,3-dimethoxy-2,3-dimethyl-1,4-dioxane-5,6-bis-diphenylmethanol (TARTROL) as a chiral building block, a set of six modular phosphine–phosphite ligands (with a 1,2-phenylene backbone) were synthesized and evaluated in the Cu-catalyzed asymmetric 1,4-addition of Grignard reagents to cyclohexenone. Ligands with bulky substituents at the ortho- and para-positions to the chiral phosphite moiety were found to be the most selective affording the 1,4-addition products with enantioselectivities of up to 84% ee.

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(2R,3R,5R,6R)-5,6-Dimethoxy-5,6-dimethyl-1,4-dioxane-2,3-dicarboxylic acid dimethyl esterC12H20O8[α]58920=-140.6 (c 1.0, CHCl3), [α]54620=-166.0 (c 1.0, CHCl3), [α]40520=-324.7 (c 1.0, CHCl3), [α]36520=-413.8 (c 1.0, CHCl3).Absolute configuration: (2R,3R,5R,6R)

(2R,3R,5R,6R)-2,3-Bis(hydroxydiphenylmethyl)-5,6-dimethoxy-5,6-dimethyl-1,4-dioxaneC34H36O6[α]58920=+50.6 (c 1.0, CHCl3), [α]54620=+62.0 (c 1.0, CHCl3), [α]40520=+154.1 (c 1.0, CHCl3), [α]36520=+226.0 (c 1.0, CHCl3)Absolute configuration: (2R,3R,5R,6R)

(2R,3R,4aR,9aR)-7-(2,4-Di-tert-butyl-6-diphenyl-phosphino-phenoxy)-2,3-dimethoxy-2,3-dimethyl-5,5,9,9-tetraphenyl-hexahydro-[1,4]dioxino[2,3-e][1,3,2]-dioxaphosphepineC60H64O7P2[α]58920=+125.7 (c 0.5, CHCl3), [α]54620=+153.5 (c 0.5, CHCl3), [α]40520=+450.2 (c 0.5, CHCl3), [α]36520=+764.0 (c 0.5, CHCl3)Absolute configuration: (2R,3R,4aR,9aR)

(2R,3R,4aR,9aR)-7-(2-Diphenylphosphino-4,6-di-tert-pentyl-phenoxy)-2,3-dimethoxy-2,3-dimethyl-5,5,9,9-tetraphenyl-hexahydro-[1,4]dioxino[2,3-e][1,3,2]-dioxaphosphepineC62H68O7P2[α]58920=+79.5 (c 0.5, CHCl3), [α]54620=+99.8 (c 0.5, CHCl3), [α]40520=+296.5 (c 0.5, CHCl3)Absolute configuration: (2R,3R,4aR,9aR)

(2R,3R,4aR,9aR)-7-(2-Diphenylphosphino-6-tert-pentyl-phenoxy)-2,3-dimethoxy-2,3-dimethyl-5,5,9,9-tetraphenyl-hexahydro-[1,4]dioxino[2,3-e][1,3,2]-dioxaphosphepineC57H58O7P2[α]58920=+137.1 (c 0.5, CHCl3), [α]54620=+169.0 (c 0.5, CHCl3), [α]40520=+470.0 (c 0.5, CHCl3), [α]36520=+777.0 (c 0.5, CHCl3)Absolute configuration: (2R,3R,4aR,9aR)

(2R,3R,4aR,9aR)-7-(2-tert-Butyl-6-diphenylphosphino-phenoxy)-2,3-dimethoxy-2,3-dimethyl-5,5,9,9-tetraphenyl-hexahydro-[1,4]dioxino[2,3-e][1,3,2]-dioxaphosphepineC56H56O7P2[α]58920=+189.3 (c 0.5, CHCl3), [α]54620=+230.7 (c 0.5, CHCl3), [α]40520=+650.9 (c 0.5, CHCl3)Absolute configuration: (2R,3R,4aR,9aR)

(2R,3R,4aR,9aR)-7-(3-Diphenylphosphino-biphenyl-2-yloxy)-2,3-dimethoxy-2,3-dimethyl-5,5,9,9-tetraphenyl-hexahydro-[1,4]dioxino[2,3-e][1,3,2]-dioxaphosphepineC58H52O7P2[α]58920=+219.1 (c 0.5, CHCl3), [α]54620=+269.4 (c 0.5, CHCl3)Absolute configuration: (2R,3R,4aR,9aR)

(2R,3R,4aR,9aR)-7-(2-Diphenylphosphino-6-methyl-phenoxy)-2,3-dimethoxy-2,3-dimethyl-5,5,9,9-tetraphenyl-hexahydro-[1,4]dioxino[2,3-e][1,3,2]-dioxaphosphepineC53H50O7P2[α]58920=+113.3 (c 0.5, CHCl3), [α]54620+138.5 (c 0.5, CHCl3), [α]40520= +375.1 (c 0.5, CHCl3), [α]36520= +598.2 (c 0.5, CHCl3)Absolute configuration: (2R,3R,4aR,9aR)