Design and synthesis of new chiral pyridine–phosphite ligands for the copper-catalyzed enantioselective conjugate addition of diethylzinc to acyclic enones

A series of new chiral pyridine–phosphite ligands have been prepared from (R)-pyridyl alcohols and BINOL-derived chlorophosphite, and successfully employed in the copper-catalyzed enantioselective conjugate addition of diethylzinc to acyclic enones. Using the simple and inexpensive CuBr2 as a precursor, the enantioselective additions to various substituted acyclic enones afforded products in high yields and good enantioselectivities (up to 92% ee).

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(R)-7-O-((S)-2,2′-O,O-(1,1′-Binaphthyl)-dioxo-phosphite)-2-phenyl-6,7-dihydro-5H-cyclopenta[b]pyridineC34H25NO3PDe >99%[α]D20=+78.1 (c 0.19, CHCl3)Source of chirality: asymmetric reductionAbsolute configuration: (Rc,Sa)

(R)-7-O-((R)-2,2′-O,O-(1,1′-Binaphthyl)-dioxo-phosphite)-2-phenyl-6,7-dihydro-5H-cyclopenta[b]pyridineC34H25NO3PDe >99%[α]D20=-221.5 (c 0.42, CHCl3)Source of chirality: asymmetric reductionAbsolute configuration: (Rc,Ra)

(R)-7-O-((S)-2,2′-O,O-(1,1′-Binaphthyl)-dioxo-phosphite)-2-chloro-6,7-dihydro-5H-cyclopenta[b]pyridineC28H20ClNO3PDe >99%[α]D20=+231.0 (c 0.16, CHCl3)Source of chirality: asymmetric reductionAbsolute configuration: (Rc,Sa)

(R)-7-O-((R)-2,2′-O,O-(1,1′-Binaphthyl)-dioxo-phosphite)-2-chloro-6,7-dihydro-5H-cyclopenta[b]pyridineC28H20ClNO3PDe >99%[α]D20=-206.1 (c 0.16, CHCl3)Source of chirality: asymmetric reductionAbsolute configuration: (Rc,Ra)

(R)-8-O-((S)-2,2′-O,O-(1,1′-Binaphthyl)-dioxo-phosphite)-2-phenyl-5,6,7,8-tetrahydroquinoineC35H27NO3PDe >99%[α]D20=+72.9 (c 0.20, CHCl3)Source of chirality: asymmetric reductionAbsolute configuration: (Rc,Sa)

(R)-8-O-((R)-2,2′-O,O-(1,1′-Binaphthyl)-dioxo-phosphite)-2-phenyl-5,6,7,8-tetrahydroquinoineC35H27NO3PDe >99%[α]D20=-290.7 (c 0.35, CHCl3)Source of chirality: asymmetric reductionAbsolute configuration: (Rc,Ra)

(R)-2-Chloro-6,7-dihydro-5H-cyclopenta[b]pyridin-7-olC8H8ClNOEe >99%[α]D20=-4.1 (c 0.39, CHCl3)Source of chirality: asymmetric reductionAbsolute configuration: (R)