TY - JOUR
T1 - Photocatalyzed Diastereoselective Isomerization of Cinnamyl Chlorides to Cyclopropanes
AU - Xu, Bin
AU - Troian-Gautier, Ludovic
AU - Dykstra, Ryan
AU - Martin, Robert T.
AU - Gutierrez, Osvaldo
AU - Tambar, Uttam K.
N1 - Funding Information:
O.G., R.D., and R.M. are grateful for financial support by the NSF (CAREER 1751568). O.G. is grateful to the University of Maryland College Park for start-up funds and computational resources from UMD Deepthought2 and MARCC/BlueCrab HPC clusters and XSEDE (CHE160082 and CHE160053). Financial support was provided to U.K.T. and B.X. by the W. W. Caruth, Jr. Endowed Scholarship, Welch Foundation (I-1748), National Institutes of Health (R01GM102604), American Chemical Society Petroleum Research Fund (59177-ND1), Teva Pharmaceuticals Marc A. Goshko Memorial Grant (60011-TEV), and Sloan Research Fellowship. L.T.-G. is a Postdoctoral researcher of the Fonds de la Recherche Scientifique-FNRS. L.T.-G. acknowledges Gerald J. Meyer for granting access to his equipment to complete the time-resolved experiments. We acknowledge Dr. Vincent Lynch (Manager of the X-ray Diffraction Lab at UT Austin) for the X-ray structural analysis.
Publisher Copyright:
Copyright © 2020 American Chemical Society.
PY - 2020/4/1
Y1 - 2020/4/1
N2 - Endergonic isomerizations are thermodynamically unfavored processes that are difficult to realize under thermal conditions. We report a photocatalytic and diastereoselective isomerization of acyclic cinnamyl chlorides to strained cyclopropanes. Quantum mechanical calculations (uM06-2X and DLPNO), including TD-DFT calculations, and experimental studies provide evidence for the energy transfer from an iridium photocatalyst to the allylic chloride substrate followed by C-Cl homolytic cleavage. Subsequent Cl⢠radical migration forms a localized triplet 1,3-diradical intermediate that, after intersystem crossing, undergoes ring-closing to form the desired product. The mild reaction conditions are compatible with a broad range of functional groups to generate chlorocyclopropanes in high yields and diastereoselectivities. A more efficient process is developed by addition of a catalytic amount of a nickel complex, and we propose a novel role for this cocatalyst to recycle an allyl chloride byproduct generated in the course of the reaction. The reaction is also shown to be stereoconvergent, as an E/Z mixture of cinnamyl chlorides furnish the anti-chlorocyclopropane product in high diastereoselectivity. We anticipate that the use of a visible light activated photocatalyst to transform substrates in combination with a transition metal catalyst to recycle byproducts back into the catalytic cycle will provide unique opportunities for the discovery of new reactivity.
AB - Endergonic isomerizations are thermodynamically unfavored processes that are difficult to realize under thermal conditions. We report a photocatalytic and diastereoselective isomerization of acyclic cinnamyl chlorides to strained cyclopropanes. Quantum mechanical calculations (uM06-2X and DLPNO), including TD-DFT calculations, and experimental studies provide evidence for the energy transfer from an iridium photocatalyst to the allylic chloride substrate followed by C-Cl homolytic cleavage. Subsequent Cl⢠radical migration forms a localized triplet 1,3-diradical intermediate that, after intersystem crossing, undergoes ring-closing to form the desired product. The mild reaction conditions are compatible with a broad range of functional groups to generate chlorocyclopropanes in high yields and diastereoselectivities. A more efficient process is developed by addition of a catalytic amount of a nickel complex, and we propose a novel role for this cocatalyst to recycle an allyl chloride byproduct generated in the course of the reaction. The reaction is also shown to be stereoconvergent, as an E/Z mixture of cinnamyl chlorides furnish the anti-chlorocyclopropane product in high diastereoselectivity. We anticipate that the use of a visible light activated photocatalyst to transform substrates in combination with a transition metal catalyst to recycle byproducts back into the catalytic cycle will provide unique opportunities for the discovery of new reactivity.
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U2 - 10.1021/jacs.0c00147
DO - 10.1021/jacs.0c00147
M3 - Article
C2 - 32129997
AN - SCOPUS:85083644827
VL - 142
SP - 6206
EP - 6215
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
SN - 0002-7863
IS - 13
ER -