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. 2007 Dec 26;129(51):16119-25.
doi: 10.1021/ja0762285. Epub 2007 Dec 4.

Catalytic asymmetric generation of (Z)-disubstituted allylic alcohols

Luca Salvi  1 , Sang-Jin Jeon, Ethan L Fisher, Patrick J Carroll, Patrick J Walsh
Affiliations

Catalytic asymmetric generation of (Z)-disubstituted allylic alcohols

Luca Salvi et al. J Am Chem Soc. .

Abstract

A one-pot method for the direct preparation of enantioenriched (Z)-disubstituted allylic alcohols is introduced. Hydroboration of 1-halo-1-alkynes with dicyclohexylborane, reaction with t-BuLi, and transmetalation with dialkylzinc reagents generate (Z)-disubstituted vinylzinc intermediates. In situ reaction of these reagents with aldehydes in the presence of a catalyst derived from (-)-MIB generates (Z)-disubstituted allylic alcohols. It was found that the resulting allylic alcohols were racemic, most likely due to a rapid addition reaction promoted by LiX (X = Br and Cl). To suppress the LiX-promoted reaction, a series of inhibitors were screened. It was found that 20-30 mol % tetraethylethylenediamine inhibited LiCl without inhibiting the chiral zinc-based Lewis acid. In this fashion, (Z)-disubstituted allylic alcohols were obtained with up to 98% ee. The asymmetric (Z)-vinylation could be coupled with tandem diastereoselective epoxidation reactions to provide epoxy alcohols and allylic epoxy alcohols with up to three contiguous stereogenic centers, enabling the rapid construction of complex building blocks with high levels of enantio- and diastereoselectivity.

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Figures

Figure 1
Figure 1
Synthon A represents (E)-disubstituted vinyl organometallics while synthon B represents (Z)-di- or trisubstituted reagents.
Figure 2
Figure 2
Possible structure of the coordinatively saturated TEEDA adduct of LiCl.
Scheme 1
Scheme 1
Application of the Sharpless-Katsuki Catalyst to the Kinetic Resolution of (E)- and (Z)-Allylic Alcohols.
Scheme 2
Scheme 2
Catalytic Asymmetric Vinylation of Aldehydes and Ketones via Hydrometallation of Terminal Alkynes, Transmetallation, and Addition.
Scheme 3
Scheme 3
Generation of (Z)-Dienyl Alcohols and Proposed Intermediates by Krische and Coworkers.
Scheme 4
Scheme 4
Our Stereospecific Method for the Synthesis of (Z)-Allylic Alcohols.
Scheme 5
Scheme 5
Optimization of the Catalytic Asymmetric Generation of (Z)-Allylic Alcohols.
Scheme 6
Scheme 6
Asymmetric Arylation of Aldehydes with TEEDA to Inhibit LiCl.
Scheme 7
Scheme 7
Tandem Asymmetric Addition/Diastereoselective Epoxidation.
Scheme 8
Scheme 8
Epoxidation of the Isolated Allylic Alcohol with VO(acac)2/TBHP and mCPBA.
Scheme 9
Scheme 9
Tandem Asymmetric Addition/Diastereo- and Chemoselective Epoxidation.
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References

    1. Katsuki T, Martin VS. Org React. 1996:1.
    1. Bonini C, Righib G. Tetrahedron. 2002;58:4981–5021.
    1. Adam W, Wirth T. Acc Chem Res. 1999;32:703–710.
    1. Katsuki T. In: Comprehensive Asymmetric Catalysis. Jacobsen EN, Pfaltz A, Yamamoto H, editors. Vol. 2. Springer; Berlin: 1999. pp. 621–648.
    1. Martín VS, Woodard SS, Katsuki T, Yamada Y, Ikeda M, Sharpless KB. J Am Chem Soc. 1981;103:6237–6240.

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