Zirconium-catalyzed asymmetric carboalumination (ZACA reaction) of 1,4-dienes

Variously substituted 1,4-dienes containing a terminal vinyl (H2CCH) group, readily undergo the ZACA reaction with Me3Al and higher alkylalanes in a 1:1 molar ratio in the presence of a catalytic amount (1–5 mol %) of bis[(1-neomenthyl)indenyl]zirconium dichloride in good yields and in good enantioselectivity (70–92% ee), thereby providing an efficient and convenient route to various alkene-containing chiral natural products. Only the reaction of the parent 1,4-pentadiene is accompanied by extensive racemization.

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(2R,4E)-2,5-Dimethyl-4-undecen-1-olC13H26OEe = 78%[α]D23=+4.4 (c 0.89, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R)

(2R)-2-Methyl-4-nhexyl-4-penten-1-olC12H24OEe = 77%[α]D23=+7.0 (c 2.1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R)

(2R,4E)-2-Methyl-4-undecen-1-olC12H24OEe = 75%[α]D23=+5.7 (c 1.66, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R)

(2R,4Z)-2-Methyl-4-trimethylsilanyl-4-nonen-1-olC13H28OSiEe = 74%[α]D23=+5.8 (c 1.5, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R)

(2R,4Z)-5-Chloro-2-methyl-4-undecen-1-olC12H23ClOEe = 80%[α]D23=+4.9 (c 1.6, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R)

(2R,4Z)-5-tert-Butyldimethylsilanyl-2-methyl-4-penten-1-olC12H26OSiEe = 70%[α]D23=+2.4 (c 1.8, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R)

(2R)-2-Ethyl-4-hexyl-4-penten-1-olC13H26OEe = 90%[α]D23=+8.2 (c 1.8, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R)

(2R,4E)-4-nButyl-2-methyl-4-nonen-1-olC14H28OEe = 76%[α]D23=+5.8 (c 0.93, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R)

(2R,4Z)-2-Ethyl-5-chloro-4-undecen-1-olC13H25ClOEe = 92%[α]D23=-2.5 (c 1.3, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R)

(2R,4Z)-5-tert-Butyldimethylsilyl-2-ethyl-4-penten-1-olC13H28OSiEe = 90%[α]D23=-4.9 (c 2.1, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (2R)