Synthesis, characterization, and structures of arylaluminum reagents and asymmetric arylation of aldehydes catalyzed by a titanium complex of an N-sulfonylated amino alcohol

A series of phenylaluminum reagents AlPhxEt3−x(L) (x = 1–3) containing adduct ligand L [Et2O, THF, OPPh3, or 4-dimethylaminopyridine (DMAP)] were synthesized and characterized. NMR studies showed that AlPhxEt3−x(L) (x = 1 or 2) exists as an equilibrium mixture of 3–4 species in solution. Solid-state structures of the phenylaluminum reagents reveal a distorted tetrahedral geometry. Asymmetric additions of phenylaluminum to 2-chlorobenzaldehyde were examined employing a titanium(IV) complex [TiL∗(OPri)2]210 (H2L∗ = (1R,2S)-2-(p-tolylsulfonylamino)-1,3-diphenyl-1-propanol) as a catalyst precursor. It was found that the adduct ligand L had a strong influence on the reactivity and the enantioselectivity in asymmetric phenyl additions to aldehydes. The phenylaluminum reagents with OPPh3 or DMAP were unreactive toward aldehydes, and AlPh3(THF) was found to be superior to AlPh3(OEt2) or AlPhEt2(THF). Asymmetric aryl additions of AlAr3(THF) to aldehydes employing a loading of 5 mol % titanium(IV) complex 10 with a strategy of a slow addition of the aldehydes over 20 min were conducted, and the reactions produced optically active secondary alcohols in high yields with excellent enantioselectivities of up to 94% ee.

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(1R,2S)-2-(p-Tolylsulfonylamino)-1,3-diphenyl-1-propanolC22H23NO3SEe = 100%[α]D25=-21.2 (c 0.5, CH2Cl2)Source of chirality: l-phenylalanineAbsolute configuration: (1R,2S)

(R)-(2-Chloro-phenyl)-phenyl-methanolC13H11ClOEe = 93%[α]D25=+33.3 (c 0.3, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-(4-Chloro-phenyl)-phenyl-methanolC13H11ClOEe = 90%[α]D25=-14.3 (c 1.0, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-(2-Bromo-phenyl)-phenyl-methanolC13H11BrOEe = 93%[α]D25=+36.7 (c 0.6, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-(4-Bromo-phenyl)-phenyl-methanolC13H11BrOEe = 90%[α]D25=-18.6 (c 0.5, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-(2-Methoxy-phenyl)-phenyl-methanolC14H14O2Ee = 94%[α]D25=+30.7 (c 0.9, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-(4-Methoxy-phenyl)-phenyl-methanolC14H14O2Ee = 90%[α]D25=+17.9 (c 1.9, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-(2-Methyl-phenyl)-phenyl-methanolC14H14OEe = 91%[α]D25=-29.3 (c 0.5, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-(4-Methyl-phenyl)-phenyl-methanolC14H14OEe = 92%[α]D25=+16.7 (c 0.54, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Phenyl-(4-trifluoromethyl-phenyl)-methanolC14H11F3OEe = 90%[α]D25=-33.0 (c 1.0, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Naphthalen-1-yl-phenyl-methanolC17H14OEe = 91%[α]D25=+48.3 (c 0.5, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-Naphthalen-2-yl-phenyl-methanolC17H14OEe = 92%[α]D25=-4.7 (c 0.5, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(S)-(E)-1,3-Diphenyl-prop-2-en-1-olC15H14OEe = 87%[α]D25=-10.5 (c 1.3, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(R)-Furan-2-yl-phenyl-methanolC11H10O2Ee = 90%[α]D25=+5.3 (c 0.5, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(S)-2,2-Dimethyl-1-phenyl-propan-1-olC11H16OEe = 74%[α]D25=-12.9 (c 0.8, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-2-Methyl-1-phenyl-propan-1-olC10H14OEe = 77%[α]D25=-24.6 (c 0.5, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-(4-Methyl-phenyl)-phenyl-methanolC14H14OEe = 91%[α]D25=-12.2 (c 0.3, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-Naphthalen-2-yl-phenyl-methanolC17H14OEe = 86%[α]D25=+8.7 (c 0.5, CH2Cl2)Source of chirality: asymmetric synthesisAbsolute configuration: (S)