Copper-catalyzed asymmetric addition of Et2Zn to 2-cyclohexen-1-one and 2-carbamoyloxy-2-cyclohexen-1-one with phosphoramidite, phosphite, and bidentate phosphite–oxazoline ligands

New biphenol-backboned phosphite–oxazoline bidentate ligands were synthesized and applied in the copper-catalyzed asymmetric conjugate additions on 2-cyclohexen-1-one with Et2Zn. In these reactions, the non-chiral oxazoline unit has demonstrated significant impact on the enantioselectivity. 2-Carbamoyloxy-2-cyclohexen-1-one is a new α-oxygenated cyclic enone substrate and was synthesized and applied to the aforementioned addition with certain phosphoramidite, phosphite, and the new bidentate ligands. Good ee has been obtained on this substrate.

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(2S,2′S,4S,4′S)-2,2′-[6-(2-(4,4-Dimethyl-4,5-dihydrooxazol-2-yl)propan-2-yloxy)dibenzo- [d,f][1,3,2]dioxaphosphepine-4,8-diyl]bis[4-ethyl-3-(mesitylsulfonyl)oxazolidine]C48H60N3O10PS2Source of chirality: amino alcohol[α]D20=-38.2 (c 0.5, CHCl3)Absolute chemistry: (2S,2′S,4S,4′S)

(2S,2′S,4S,4′S)-2,2′-[2,10-Di-tert-butyl-6-(2-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)propan-2-yl-oxy)dibenzo[d,f][1,3,2]dioxaphosphepine-4,8-diyl]bis[4-sec-butyl-3-(4-tert-butylphenylsulfonyl)oxazolidine]C62H88N3O10PS2Source of chirality: amino alcohol[α]D20=-3.4 (c 0.5, CHCl3)Absolute chemistry: (2S,2′S,4S,4′S)

(2S,2′S,4S,4′S)-2,2′-[6-(2-(4,4-Dimethyl-4,5-dihydrooxazol-2-yl)propan-2-yloxy)dibenzo-[d,f][1,3,2]dioxaphosphepine-4,8-diyl]bis[4-isobutyl-3-(mesitylsulfonyl)oxazolidine]C52H68N3O10PS2Source of chirality: amino alcohol[α]D20=+30.2 (c 0.5, CHCl3)Absolute chemistry: (2S,2′S,4S,4′S)

(2S,2′S,4S,4′S)-2,2′-[2,10-Di-tert-butyl-6-(2-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)propan-2-yl-oxy)dibenzo[d,f][1,3,2]dioxaphosphepine-4,8-diyl]bis[4-ethyl-3-tosyloxazolidine]C52H68N3O10PS2Source of chirality: amino alcohol[α]D20=+3.3 (c 0.5, CHCl3)Absolute chemistry: 2S,2′S,4S,4′S)

2-(tert-Butyldimethylsilyloxy)-6-ethylcyclohex-1-enyl N,N-diisopropylcarbamateC21H41NO3SiSource of chirality: asymmetric conjugate addition[α]D20=+19.0 (c 1, CHCl3)Ee = 82%Absolute chemistry not determined