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
. 2017 Jun 21;139(24):8114-8117.
doi: 10.1021/jacs.7b04374. Epub 2017 Jun 12.

Enantioselective Formation of CF3-Bearing All-Carbon Quaternary Stereocenters via C-H Functionalization of Methanol: Iridium Catalyzed Allene Hydrohydroxymethylation

Michael Holmes  1 , Khoa D Nguyen  1 , Leyah A Schwartz  1 , Tom Luong  1 , Michael J Krische  1
Affiliations

Enantioselective Formation of CF3-Bearing All-Carbon Quaternary Stereocenters via C-H Functionalization of Methanol: Iridium Catalyzed Allene Hydrohydroxymethylation

Michael Holmes et al. J Am Chem Soc. .

Abstract

Using an iridium catalyst modified by PhanePhos, CF3-allenes react with methanol to form branched products of hydrohydroxymethylation as single regioisomers with excellent levels of enantiomeric enrichment. This hydrogen autotransfer process enables catalytic enantioselective formation of acyclic CF3-bearing all-carbon quaternary stereocenters in the absence of stoichiometric metals or byproducts.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1
Catalytic enantioselective formation of acyclic CF3-bearing all-carbon quaternary stereocenters.
Scheme 2
Scheme 2
General catalytic mechanism and deuterium labelling studies.a aYields of material isolated by silica gel chromatography. The extent deuterium incorporation was determined by HRMS and 1H and 2H NMR analysis. See Supporting Information for further experimental details. Haptomeric equilibria and equilibria involving alkoxy-bridged dimers are not depicted.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. For selected reviews on the enantioselective formation of all-carbon quaternary centers, see: Fuji K. Chem. Rev. 1993;93:2037.Corey EJ, Guzman-Perez A. Angew. Chem. Int. Ed. 1998;37:388.Bella M, Gasperi T. Synthesis. 2009:1583.Shimizu M. Angew. Chem. Int. Ed. 2011;50:5998.Hong AY, Stoltz BM. Eur. J. Org. Chem. 2013:2745.Minko Y, Marek I. Chem. Comm. 2014:12597.Marek I, Minko Y, Pasco M, Mejuch T, Gilboa N, Chechik H, Das JP. J. Am. Chem. Soc. 2014;136:2682.Quasdorf KW, Overman LE. Nature. 2014;516:181.Liu Y, Han S-J, Liu W-B, Stoltz BM. Acc. Chem. Res. 2015;48:740.Zeng X-P, Cao Z-Y, Wang Y-H, Zhou F, Zhou J. Chem. Rev. 2016;116:7330.

    1. For recent examples of the catalytic enantioselective formation of acyclic all-carbon quaternary centers, see: Dabrowski JA, Gao F, Hoveyda AH. J. Am. Chem. Soc. 2011;133:4778.Zhang P, Le H, Kyne RE, Morken JP. J. Am. Chem. Soc. 2011;133:9716.Jung B, Hoveyda AH. J. Am. Chem. Soc. 2012;134:1490.Gao L, Kang BC, Ryu DH. J. Am. Chem. Soc. 2013;135:14556.Liu W-B, Reeves CM, Stoltz BM. J. Am. Chem. Soc. 2013;135:17298.Mei T-S, Patel HH, Sigman MS. Nature. 2014;508:340.Zhang C, Santiago CB, Crawford JM, Sigman MS. J. Am. Chem. Soc. 2015;137:15668.Zhou Q, Cobb KM, Tan T, Watson MP. J. Am. Chem. Soc. 2016;138:12057.Patel HH, Sigman MS. J. Am. Chem. Soc. 2016;138:14226.

    1. For catalytic enantioselective formation of acyclic all-carbon quaternary centers via C-C bond forming transfer hydrogenation, see: Feng J, Garza VJ, Krische MJ. J. Am. Chem. Soc. 2014;136:8911.Feng J, Noack F, Krische MJ. J. Am. Chem. Soc. 2016;138:12364.Nguyen KD, Herkommer D, Krische MJ. J. Am. Chem. Soc. 2016;138:14210.Guo Y-A, Lee W, Krische MJ. Chem. Eur. J. 2017;23:2557.

    1. For catalytic enantioselective conjugate addition to form acyclic CF3-bearing quaternary stereocenters, see: Kawai H, Okusu S, To-kunaga E, Sato H, Shiro M, Shibata N. Angew. Chem. Int. Ed. 2012;51:4959.Kawai H, Yuan Z, Kitayama T, Tokunaga E, Shibata N. Angew. Chem. Int. Ed. 2013;52:5575.Gao J-R, Wu H, Xiang B, Yu W-B, Han L, Jia Y-X. J. Am. Chem. Soc. 2013;135:2983.Chen Q, Wang G, Jiang X, Xu Z, Lin L, Wang R. Org. Lett. 2014;16:1394.Kwiatkowski P, Cholewiak A, Kasztelan A. Org. Lett. 2014;16:5930.Ma C-H, Kang T-R, He L, Liu Q-Z. Eur. J. Org. Chem. 2014:3981.Sanz-Marco A, Blay G, Vila C, Pedro JR. Org. Lett. 2016;18:3538.Zhu Y, Dong Z, Cheng X, Zhong X, Liu X, Lin Li, Shen Z, Yang P, Li Y, Wang H, Yan W, Wang K, Wang R. Org. Lett. 2016;18:3546.Lai X, Zha G, Liu W, Xu Y, Sun P, Xia T, Shen Y. Synlett. 2016;27:1983.Hou X, Ma H, Zhang Z, Xie L, Qin Z, Fu B. Chem. Commun. 2016:1470.Hao X-Q, Wang C, Liu S-L, Wang X, Wang L, Gong J-F, Song M-P. Org. Chem. Front. 2017;4:308.

    1. Kimura M, Yamazaki T, Kitazume T, Kubota T. Org. Lett. 2004;6:4651. - PubMed
    2. Tsuchida K, Senda Y, Nakajima K, Nishi-bayashi Y. Angew. Chem. Int. Ed. 2016;55:9728. - PubMed

Publication types