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
. 2015 Aug 26;137(33):10524-7.
doi: 10.1021/jacs.5b07061. Epub 2015 Aug 12.

Enantioselective Synthesis of Carbo- and Heterocycles through a CuH-Catalyzed Hydroalkylation Approach

Yi-Ming Wang  1 , Nicholas C Bruno  1 , Ángel L Placeres  1 , Shaolin Zhu  1 , Stephen L Buchwald  1
Affiliations

Enantioselective Synthesis of Carbo- and Heterocycles through a CuH-Catalyzed Hydroalkylation Approach

Yi-Ming Wang et al. J Am Chem Soc. .

Abstract

The enantioselective, intramolecular hydroalkylation of halide-tethered styrenes has been achieved through a copper hydride-catalyzed process. This approach allowed for the synthesis of enantioenriched cyclobutanes, cyclopentanes, indanes, and six-membered N- and O-heterocycles. This protocol was applied to the synthesis of the commercial serotonin reuptake inhibitor (-)-paroxetine.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Hydroalkylation as a strategy for the construction of unfunctionalized C(sp3)–C(sp3) bonds.
Figure 2
Figure 2
(A) Representative saturated 4-, 5-, and 6-membered rings found in pharmaceuticals and natural products. (B) Proposed catalytic cycle for the CuH-catalyzed enantioselective hydroalkylation.
Figure 3
Figure 3
X-ray crystallographic structure of 2o (ellipsoids at 50% probability).
Scheme 1
Scheme 1. Synthesis of (−)-Paroxetine
See this image and copyright information in PMC

References

    1. For selected reviews on the enantioselective catalytic formation of C(sp3)–C(sp3) bonds, see:

    2. Hoveyda A. H.; Morken J. P. Angew. Chem., Int. Ed. Engl. 1996, 35, 1262.10.1002/anie.199612621. - DOI
    3. Kobayashi S.; Ishitani H. Chem. Rev. 1999, 99, 1069.10.1021/cr980414z. - DOI - PubMed
    4. Fürstner A. Chem. Rev. 1999, 99, 991.10.1021/cr9703360. - DOI - PubMed
    5. Johnson J. S.; Evans D. A. Acc. Chem. Res. 2000, 33, 325.10.1021/ar960062n. - DOI - PubMed
    6. Mikami K.; Terada M.; Matsuzawa H. Angew. Chem., Int. Ed. 2002, 41, 3554.10.1002/1521-3773(20021004)41:19<3554::AID-ANIE3554>3.0.CO;2-P. - DOI - PubMed
    7. Davies H. M. L.; Beckwith R. E. J. Chem. Rev. 2003, 103, 2861.10.1021/cr0200217. - DOI - PubMed
    8. Ooi T.; Maruoka K. Angew. Chem., Int. Ed. 2007, 46, 4222.10.1002/anie.200601737. - DOI - PubMed
    9. Gaunt M. J.; Johansson C. C. C.; McNally A.; Vo N. T. Drug Discovery Today 2007, 12, 8.10.1016/j.drudis.2006.11.004. - DOI - PubMed
    10. Shibasaki M.; Kanai M. Chem. Rev. 2008, 108, 2853.10.1021/cr078340r. - DOI - PubMed
    11. Trost B. M.; Brindle C. S. Chem. Soc. Rev. 2010, 39, 1600.10.1039/b923537j. - DOI - PMC - PubMed
    12. Terada M. Bull. Chem. Soc. Jpn. 2010, 83, 101.10.1246/bcsj.20090268. - DOI
    13. Hassan A.; Krische M. J. Org. Process Res. Dev. 2011, 15, 1236.10.1021/op200195m. - DOI - PMC - PubMed
    14. Negishi E.-i. ARKIVOC 2010, 2011viii34.10.3998/ark.5550190.0012.803. - DOI - PubMed
    15. Watson I. D. G.; Toste F. D. Chem. Sci. 2012, 3, 2899.10.1039/c2sc20542d. - DOI
    16. Yang L.; Huang H. Catal. Sci. Technol. 2012, 2, 1099.10.1039/c2cy20111a. - DOI
    17. Scheffler U.; Mahrwald R. Chem. - Eur. J. 2013, 19, 14346.10.1002/chem.201301996. - DOI - PubMed
    18. Tsubogo T.; Ishiwata T.; Kobayashi S. Angew. Chem., Int. Ed. 2013, 52, 6590.10.1002/anie.201210066. - DOI - PubMed
    19. Šebesta R. ChemCatChem 2013, 5, 1069.10.1002/cctc.201200926. - DOI
    20. Tasker S. Z.; Standley E. A.; Jamison T. F. Nature 2014, 509, 299.10.1038/nature13274. - DOI - PMC - PubMed

    21. For selected methods based on stoichiometric auxiliaries, see:

    22. Meyers A. I. Acc. Chem. Res. 1978, 11, 375.10.1021/ar50130a002. - DOI
    23. Evans D. A.; Bartroli J.; Shih T. L. J. Am. Chem. Soc. 1981, 103, 2127.10.1021/ja00398a058. - DOI
    24. Myers A. G.; Yang B. H.; Chen H.; McKinstry L.; Kopecky D. J.; Gleason J. L. J. Am. Chem. Soc. 1997, 119, 6496.10.1021/ja970402f. - DOI
    25. Ellman J. A.; Owens T. D.; Tang T. P. Acc. Chem. Res. 2002, 35, 984.10.1021/ar020066u. - DOI - PubMed
    26. Job A.; Janeck C. F.; Bettray W.; Peters R.; Enders D. Tetrahedron 2002, 58, 2253.10.1016/S0040-4020(02)00080-7. - DOI

    27. For an overview of enantioselective C—C bond-forming reactions applied to complex molecule synthesis, see:

    28. Corey E. J.; Kürti L.. Enantioselective Chemical Synthesis; Academic Press: San Diego, 2013.

    1. For examples of the enantioselective, catalytic generation of C(sp3)–C(sp3) bonds remote from reactive functional groups, see:

    2. Pino P.; Cioni P.; Wei J. J. Am. Chem. Soc. 1987, 109, 6189.10.1021/ja00254a052. - DOI
    3. Long J.; Du H.; Li K.; Shi Y. Tetrahedron Lett. 2005, 46, 2737.10.1016/j.tetlet.2005.02.161. - DOI
    4. Arp F. O.; Fu G. C. J. Am. Chem. Soc. 2005, 127, 10482.10.1021/ja053751f. - DOI - PubMed
    5. Saito B.; Fu G. C. J. Am. Chem. Soc. 2008, 130, 6694.10.1021/ja8013677. - DOI - PubMed
    1. Corey E. J.; Posner G. H. J. Am. Chem. Soc. 1967, 89, 3911.10.1021/ja00991a049. - DOI
    2. Whitesides G. M.; Fischer W. P.; San Filippo J.; Bashe R. W.; House H. O. J. Am. Chem. Soc. 1969, 91, 4871.10.1021/ja01045a049. - DOI

    3. For the copper-catalyzed coupling of alkyl halides and Grignard reagents, see:

    4. Fouquet G.; Schlosser M. Angew. Chem., Int. Ed. Engl. 1974, 13, 82.10.1002/anie.197400821. - DOI

    1. For the construction of C(sp3)–C(sp3) bonds through Cu-catalyzed alkene carboboration, see:

    2. Ito H.; Kosaka Y.; Nonoyama K.; Sasaki Y.; Sawamura M. Angew. Chem., Int. Ed. 2008, 47, 7424.10.1002/anie.200802342. - DOI - PubMed
    3. Ito H.; Toyoda T.; Sawamura M. J. Am. Chem. Soc. 2010, 132, 5990.10.1021/ja101793a. - DOI - PubMed
    4. Zhong C.; Kunii S.; Kosaka Y.; Sawamura M.; Ito H. J. Am. Chem. Soc. 2010, 132, 11440.10.1021/ja103783p. - DOI - PubMed
    5. Kubota K.; Yamamoto E.; Ito H. J. Am. Chem. Soc. 2013, 135, 2635.10.1021/ja3104582. - DOI - PubMed
    6. Yoshida H.; Kageyuki I.; Takaki K. Org. Lett. 2013, 15, 952.10.1021/ol4001526. - DOI - PubMed
    1. Zhu S.; Niljianskul N.; Buchwald S. L. J. Am. Chem. Soc. 2013, 135, 15746.10.1021/ja4092819. - DOI - PMC - PubMed
    2. Zhu S.; Buchwald S. L. J. Am. Chem. Soc. 2014, 136, 15913.10.1021/ja509786v. - DOI - PMC - PubMed
    3. Niljianskul N.; Zhu S.; Buchwald S. L. Angew. Chem., Int. Ed. 2015, 54, 1638.10.1002/anie.201410326. - DOI - PMC - PubMed
    4. Shi S.; Buchwald S. L. Nat. Chem. 2014, 7, 38.10.1038/nchem.2131. - DOI - PMC - PubMed

    5. For the independent development of a related system, see:

    6. Miki Y.; Hirano K.; Satoh T.; Miura M. Angew. Chem., Int. Ed. 2013, 52, 10830.10.1002/anie.201304365. - DOI - PubMed
    7. Miki Y.; Hirano K.; Satoh T.; Miura M. Org. Lett. 2014, 16, 1498.10.1021/ol5003219. - DOI - PubMed

    8. For a CuH-catalyzed C—C bond-forming reaction resulting in the enantioselective formation of indolines, see:

    9. Ascic E.; Buchwald S. L. J. Am. Chem. Soc. 2015, 137, 4666.10.1021/jacs.5b02316. - DOI - PMC - PubMed

Publication types

LinkOut - more resources