TY - JOUR
T1 - Catalytic Asymmetric Hydrogen Atom Transfer
T2 - Enantioselective Hydroamination of Alkenes
AU - Hejna, Benjamin G.
AU - Ganley, Jacob M.
AU - Shao, Huiling
AU - Tian, Haowen
AU - Ellefsen, Jonathan D.
AU - Fastuca, Nicholas J.
AU - Houk, Kendall N.
AU - Miller, Scott J.
AU - Knowles, Robert R.
N1 - Funding Information:
J.M.G. acknowledges Bristol Myers Squibb for a graduate fellowship. The authors thank Anthony Metrano and Nicholas Chiappini for helpful discussions. The authors thank Glenn Atkinson, the Princeton Physics Machine Shop, Brian Koronkiewicz, and Jackson Deobald for assistance with photoreactor design and construction. The authors also thank Ken Conover (PhotoNMR), István Pelczer (PhotoNMR), and Phil Jeffrey (X-ray Crystallography). DFT calculations were performed on the IDRE Hoffman2 cluster at the University of California, Los Angeles, and the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by the NSF (OCI1053575). Funding for this work was provided by the NIH (R35 GM134893 to R.R.K.), NIGMS (R35 132092 to S.J.M.), and the NSF (CHE-2153972 to K.N.H.).
Funding Information:
J.M.G. acknowledges Bristol Myers Squibb for a graduate fellowship. The authors thank Anthony Metrano and Nicholas Chiappini for helpful discussions. The authors thank Glenn Atkinson, the Princeton Physics Machine Shop, Brian Koronkiewicz, and Jackson Deobald for assistance with photoreactor design and construction. The authors also thank Ken Conover (PhotoNMR), István Pelczer (PhotoNMR), and Phil Jeffrey (X-ray Crystallography). DFT calculations were performed on the IDRE Hoffman2 cluster at the University of California, Los Angeles, and the Extreme Science and Engineering Discovery Environment (XSEDE), which is supported by the NSF (OCI1053575).
Funding Information:
Funding for this work was provided by the NIH (R35 GM134893 to R.R.K.), NIGMS (R35 132092 to S.J.M.), and the NSF (CHE-2153972 to K.N.H.).
Publisher Copyright:
© 2023 American Chemical Society.
PY - 2023/7/26
Y1 - 2023/7/26
N2 - We report a highly enantioselective radical-based hydroamination of enol esters with sulfonamides jointly catalyzed by an Ir photocatalyst, Brønsted base, and tetrapeptide thiol. This method is demonstrated for the formation of 23 protected β-amino-alcohol products, achieving selectivities up to 97:3 er. The stereochemistry of the product is set through selective hydrogen atom transfer from the chiral thiol catalyst to a prochiral C-centered radical. Structure-selectivity relationships derived from structural variation of both the peptide catalyst and olefin substrate provide key insights into the development of an optimal catalyst. Experimental and computational mechanistic studies indicate that hydrogen-bonding, π-π stacking, and London dispersion interactions are contributing factors for substrate recognition and enantioinduction. These findings further the development of radical-based asymmetric catalysis and contribute to the understanding of the noncovalent interactions relevant to such transformations.
AB - We report a highly enantioselective radical-based hydroamination of enol esters with sulfonamides jointly catalyzed by an Ir photocatalyst, Brønsted base, and tetrapeptide thiol. This method is demonstrated for the formation of 23 protected β-amino-alcohol products, achieving selectivities up to 97:3 er. The stereochemistry of the product is set through selective hydrogen atom transfer from the chiral thiol catalyst to a prochiral C-centered radical. Structure-selectivity relationships derived from structural variation of both the peptide catalyst and olefin substrate provide key insights into the development of an optimal catalyst. Experimental and computational mechanistic studies indicate that hydrogen-bonding, π-π stacking, and London dispersion interactions are contributing factors for substrate recognition and enantioinduction. These findings further the development of radical-based asymmetric catalysis and contribute to the understanding of the noncovalent interactions relevant to such transformations.
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U2 - 10.1021/jacs.3c04591
DO - 10.1021/jacs.3c04591
M3 - Article
C2 - 37432783
AN - SCOPUS:85165714575
SN - 0002-7863
VL - 145
SP - 16118
EP - 16129
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 29
ER -