TY - JOUR
T1 - Switchable, Reagent-Controlled Diastereodivergent Photocatalytic Carbocyclisation of Imine-Derived α-Amino Radicals
AU - Maitland, J. Andrew P.
AU - Leitch, Jamie A.
AU - Yamazaki, Ken
AU - Christensen, Kirsten E.
AU - Cassar, Doyle J.
AU - Hamlin, Trevor A.
AU - Dixon, Darren J.
N1 - Funding Information:
J.A.P.M. thanks AstraZeneca for a studentship. J.A.L. wishes to thank the Leverhulme Trust (RPG-2017-069) for a research fellowship. K.Y. thanks the Honjo International Scholarship Foundation for a postgraduate scholarship. T.A.H. thanks The Netherlands Organization for Scientific Research (NWO) for financial support. Computational work was carried out on the Dutch national e-infrastructure with the support of SURF Cooperative. The authors thank Roman Kučera for designing and 3D-printing equipment for the photoflow experiments.
Funding Information:
J.A.P.M. thanks AstraZeneca for a studentship. J.A.L. wishes to thank the Leverhulme Trust (RPG‐2017‐069) for a research fellowship. K.Y. thanks the Honjo International Scholarship Foundation for a postgraduate scholarship. T.A.H. thanks The Netherlands Organization for Scientific Research (NWO) for financial support. Computational work was carried out on the Dutch national e‐infrastructure with the support of SURF Cooperative. The authors thank Roman Kučera for designing and 3D‐printing equipment for the photoflow experiments.
Publisher Copyright:
© 2021 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH
PY - 2021/11/2
Y1 - 2021/11/2
N2 - A reagent-controlled stereodivergent carbocyclisation of aryl aldimine-derived, photocatalytically generated, α-amino radicals possessing adjacent conjugated alkenes, affording either bicyclic or tetracyclic products, is described. Under net reductive conditions using commercial Hantzsch ester, the α-amino radical species underwent a single stereoselective cyclisation to give trans-configured amino-indane structures in good yield, whereas using a substituted Hantzsch ester as a milder reductant afforded cis-fused tetracyclic tetrahydroquinoline frameworks, resulting from two consecutive radical cyclisations. Judicious choice of the reaction conditions allowed libraries of both single and dual cyclisation products to be synthesised with high selectivity, notable predictability, and good-to-excellent yields. Computational analysis employing DFT revealed the reaction pathway and mechanistic rationale behind this finely balanced yet readily controlled photocatalytic system.
AB - A reagent-controlled stereodivergent carbocyclisation of aryl aldimine-derived, photocatalytically generated, α-amino radicals possessing adjacent conjugated alkenes, affording either bicyclic or tetracyclic products, is described. Under net reductive conditions using commercial Hantzsch ester, the α-amino radical species underwent a single stereoselective cyclisation to give trans-configured amino-indane structures in good yield, whereas using a substituted Hantzsch ester as a milder reductant afforded cis-fused tetracyclic tetrahydroquinoline frameworks, resulting from two consecutive radical cyclisations. Judicious choice of the reaction conditions allowed libraries of both single and dual cyclisation products to be synthesised with high selectivity, notable predictability, and good-to-excellent yields. Computational analysis employing DFT revealed the reaction pathway and mechanistic rationale behind this finely balanced yet readily controlled photocatalytic system.
KW - diastereoselectivity
KW - imines
KW - photocatalysis
KW - redox reactions
KW - reduction
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U2 - 10.1002/anie.202107253
DO - 10.1002/anie.202107253
M3 - Article
C2 - 34449968
AN - SCOPUS:85117048913
SN - 1433-7851
VL - 60
SP - 24116
EP - 24123
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 45
ER -