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. 2015 Mar 18;137(10):3462-5.
doi: 10.1021/ja5130836. Epub 2015 Mar 9.

Palladium-catalyzed enantioselective Heck alkenylation of acyclic alkenols using a redox-relay strategy

Harshkumar H Patel  1 , Matthew S Sigman  1
Affiliations

Palladium-catalyzed enantioselective Heck alkenylation of acyclic alkenols using a redox-relay strategy

Harshkumar H Patel et al. J Am Chem Soc. .

Abstract

We report a highly enantioselective intermolecular Heck reaction of alkenyl triflates and acyclic primary or racemic secondary alkenols. The mild reaction conditions permit installation of a wide range of alkenyl groups at positions β, γ, or δ to a carbonyl group in high enantioselectivity. The success of this reaction is attributed to the use of electron-withdrawing alkenyl triflates, which offer selective β-hydride elimination followed by migration of the catalyst through the alkyl chain to give the alkenylated carbonyl products. The synthetic utility of the process is demonstrated by a two-step modification of a reaction product to yield a tricyclic core structure, present in various natural products.

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Conflict of interest statement

Notes

The authors declare no competing financial interests.

Figures

Figure 1
Figure 1
a) Enantioselective arylative relay Heck reaction b) Proposed enantioselective alkenylative relay Heck reaction c) Mechanistic hypothesis d) Potential challenge e) Preliminary result
Figure 2
Figure 2
a) Approach to overcome the formation of π-allyl intermediates b) Successful enantioselective alkenylative relay Heck reaction
Scheme 1
Scheme 1
Processing of a relay Heck product to resemble a natural product core structure.
See this image and copyright information in PMC

References

    1. Nicolaou KC, Sorensen EJ. Classics in Total Synthesis. VCH; Weinheim: 1996.
    2. Nicolaou KC, Snyder SA. Classics in Total Synthesis II. More Targets, Strategies, Methods. Wiley-VCH; Weinheim: 2003.
    3. Saklani A, Kutty SK. Drug Discovery Today. 2008;13:161. - PubMed
    4. Liu KK-C, Sakya LS. Mini-Rev Med Chem. 2004;4:1105. - PubMed

    1. For reports on asymmetric conjugate additions, see:

    2. Nakao Y, Chen IH, Hiyama T, Ichikawa I, Duan W, Shintani R, Hayashi T. J Am Chem Soc. 2007;129:9137. - PubMed
    3. Oi S, Sato T, Inoue Y. Tetrahedron Lett. 2004;45:5051.
    4. Nicolaou KC, Tang W, Dagneau P, Faraoni R. Angew Chem Int Ed. 2005;44:3874. - PubMed
    5. Hayashi T, Yamasaki K. Chem Rev. 2003;103:2829. - PubMed

    1. For reports on asymmetric allylic displacement, see:

    2. Hamilton J, Sarlah D, Carreira EM. J Am Chem Soc. 2013;135:994. - PubMed
    3. Akiyama K, Gao F, Hoveyda AH. Angew Chem Int Ed. 2010;49:419. - PMC - PubMed
    4. Gao F, McGrath KP, Lee Y, Hoveyda AH. J Am Chem Soc. 2010;132:14315. - PMC - PubMed
    5. Gao F, Carr JL, Hoveyda AH. Angew Chem, Int Ed. 2012;51:6613. - PMC - PubMed
    6. Shintani R, Takatsu K, Takeda M, Hayashi T. Angew Chem, Int Ed. 2011;50:8656. - PubMed
    7. Jung B, Hoveyda AH. J Am Chem Soc. 2012;134:1490. - PMC - PubMed

    1. Other methods for the enantioselective introduction of alkenyl groups, see

    2. Biradar DB, Gau H-M. Org Lett. 2009;11:499. - PubMed
    3. Pu L, Yu H-B. Chem Rev. 2001;101:757. and references within. - PubMed
    4. Page JP, RajanBabu TV. J Am Chem Soc. 2012;134:6556. and references within. - PMC - PubMed
    5. Stevens JM, MacMillan DWC. J Am Chem Soc. 2013;135:11756. and references within. - PMC - PubMed
    6. Cherney AH, Reisman SE. J Am Chem Soc. 2014;136:14365. - PMC - PubMed
    1. Dounay AB, Overman LE. Chem Rev. 2003;103:2945. and references therein. - PubMed

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