Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 May 11;138(18):5821-4.
doi: 10.1021/jacs.6b03086. Epub 2016 Apr 29.

Enantioselective CuH-Catalyzed Reductive Coupling of Aryl Alkenes and Activated Carboxylic Acids

Jeffrey S Bandar  1 , Erhad Ascic  1 , Stephen L Buchwald  1
Affiliations

Enantioselective CuH-Catalyzed Reductive Coupling of Aryl Alkenes and Activated Carboxylic Acids

Jeffrey S Bandar et al. J Am Chem Soc. .

Abstract

A new method for the enantioselective reductive coupling of aryl alkenes with activated carboxylic acid derivatives via copper hydride catalysis is described. Dual catalytic cycles are proposed, with a relatively fast enantioselective hydroacylation cycle followed by a slower diastereoselective ketone reduction cycle. Symmetrical aryl carboxyclic anhydrides provide access to enantioenriched α-substituted ketones or alcohols with excellent stereoselectivity and functional group tolerance.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. (a) Prior Work in Aryl Alkene Reductive Coupling to Acyl Electrophiles; (b) Proposed Access to Chiral Ketones or Alcohols; (c) Proposed Catalytic Cycles
Scheme 2
Scheme 2. (a) Enantioselective Ketone Synthesis and (b) Reduction
All yields represent average isolated yields of two runs performed with 1 mmol of alkene. Reaction run at ambient temperature.
See this image and copyright information in PMC

References

    1. Corey E. J.; Kürti L.. Enantioselective Chemical Synthesis: Methods, Logic and Practice; Direct Book Publishing: Dallas, 2010.

    1. For selected reviews on hydroacylation:

    2. Yang L.; Huang H. Chem. Rev. 2015, 115, 3468.10.1021/cr500610p. - DOI - PubMed
    3. Leung J. C.; Krische M. J. Chem. Sci. 2012, 3, 2202.10.1039/c2sc20350b. - DOI
    4. Willis M. C. Chem. Rev. 2010, 110, 725.10.1021/cr900096x. - DOI - PubMed
    5. Park Y. J.; Park J.-W.; Jun C.-H. Acc. Chem. Res. 2008, 41, 222.10.1021/ar700133y. - DOI - PubMed

    1. For selected reviews on alkene reductive coupling:

    2. Ketcham J. M.; Shin I.; Montgomery T. P.; Krische M. J. Angew. Chem., Int. Ed. 2014, 53, 9142.10.1002/anie.201403873. - DOI - PMC - PubMed
    3. Dechert-Schmitt A.-M. R.; Schmitt D. C.; Gao X.; Itoh T.; Krische M. J. Nat. Prod. Rep. 2014, 31, 504.10.1039/c3np70076c. - DOI - PMC - PubMed
    4. Bower J. F.; Kim I. S.; Patman R. L.; Krische M. J. Angew. Chem., Int. Ed. 2009, 48, 34.10.1002/anie.200802938. - DOI - PMC - PubMed
    5. Ngai M.-Y.; Kong J.-R.; Krische M. J. J. Org. Chem. 2007, 72, 1063.10.1021/jo061895m. - DOI - PubMed
    6. Montgomery J.Organonickel Chemistry. In Organometallics in Synthesis; Lipshutz B. H., Ed.; John Wiley & Sons, Inc.: Hoboken, 2013; pp 319–428.
    7. Ng S.-S.; Ho C.-Y.; Schleicher K. D.; Jamison T. F. Pure Appl. Chem. 2008, 80, 929.10.1351/pac200880050929. - DOI - PMC - PubMed
    8. Reichard H. A.; Micalizio G. C. Chem. Sci. 2011, 2, 573.10.1039/C0SC00394H. - DOI - PMC - PubMed
    9. Micalizio G. C.; Hale S. B. Acc. Chem. Res. 2015, 48, 663.10.1021/ar500408e. - DOI - PMC - PubMed
    10. Ho C.-Y.; Schleicher K. D.; Chan C.-W.; Jamison T. F. Synlett 2009, 2565.10.1055/s-0029-1217747. - DOI - PMC - PubMed
    11. Sato F.; Urabe H.; Okamoto S. Chem. Rev. 2000, 100, 2835.10.1021/cr990277l. - DOI - PubMed

    1. For reviews on asymmetric hydroacylation, see:

    2. Murphy S. K.; Dong V. M. Chem. Commun. 2014, 50, 13645.10.1039/C4CC02276A. - DOI - PMC - PubMed
    3. González-Rodríguez C.; Willis M. C. Pure Appl. Chem. 2011, 83, 577.10.1351/PAC-CON-10-09-23. - DOI

    4. For selected enantioselective intermolecular hydroacylation reactions, see:

    5. Liu F.; Bugaut X.; Schedler M.; Fröhlich R.; Glorius F. Angew. Chem., Int. Ed. 2011, 50, 12626.10.1002/anie.201106155. - DOI - PubMed
    6. Stemmler R. T.; Bolm C. Adv. Synth. Catal. 2007, 349, 1185.10.1002/adsc.200600583. - DOI
    7. Shibata Y.; Tanaka K. J. Am. Chem. Soc. 2009, 131, 12552.10.1021/ja905908z. - DOI - PubMed
    8. Coulter M. M.; Kou K. G. M.; Galligan B.; Dong V. M. J. Am. Chem. Soc. 2010, 132, 16330.10.1021/ja107198e. - DOI - PubMed
    9. Phan D. H. T.; Kou K. G. M.; Dong V. M. J. Am. Chem. Soc. 2010, 132, 16354.10.1021/ja107738a. - DOI - PubMed
    10. Osborne J. D.; Randell-Sly H. E.; Currie G. S.; Cowley A. R.; Willis M. C. J. Am. Chem. Soc. 2008, 130, 17232.10.1021/ja8069133. - DOI - PubMed

    1. For reviews on reductive aldol, Mannich, and Michael reactions:

    2. Nishiyama H.; Shiomi T. Top. Curr. Chem. 2007, 279, 105.10.1007/128_2007_126. - DOI
    3. Guo H.-C.; Ma J.-A. Angew. Chem., Int. Ed. 2006, 45, 354.10.1002/anie.200500195. - DOI - PubMed
    4. Jang H.-Y.; Krische M. J. Eur. J. Org. Chem. 2004, 3953.10.1002/ejoc.200400270. - DOI - PubMed

    5. Selected Cu-catalyzed reductive coupling reactions:

    6. Lipshutz B. H.; Amorelli B.; Unger J. B. J. Am. Chem. Soc. 2008, 130, 14378.10.1021/ja8045475. - DOI - PubMed
    7. Zhao D.; Oisaki K.; Kanai M.; Shibasaki M. J. Am. Chem. Soc. 2006, 128, 14440.10.1021/ja0652565. - DOI - PubMed
    8. Deschamp J.; Chuzel O.; Hannedouche J.; Riant O. Angew. Chem., Int. Ed. 2006, 45, 1292.10.1002/anie.200503791. - DOI - PubMed

Publication types

LinkOut - more resources