TY - JOUR
T1 - Ni-Catalyzed Regioselective Dicarbofunctionalization of Unactivated Olefins by Tandem Cyclization/Cross-Coupling and Application to the Concise Synthesis of Lignan Natural Products
AU - Kc, Shekhar
AU - Basnet, Prakash
AU - Thapa, Surendra
AU - Shrestha, Bijay
AU - Giri, Ramesh
N1 - Funding Information:
We thank the University of New Mexico (UNM) and the National Science Foundation (NSF CHE-1554299) for financial support and upgrades to the NMR (NSF grants CHE08-40523 and CHE09-46690) and MS Facilities. We also thank Prof. Abhaya K. Datye at the Department of Chemical & Biological Engineering (UNM) and Prof. Wei Wang at the Department of Chemistry & Chemical Biology (UNM) for providing us with the generous access to their chiral HPLC's.
PY - 2018/3/2
Y1 - 2018/3/2
N2 - We disclose a (terpy)NiBr2-catalyzed reaction protocol that regioselectively difunctionalizes unactivated olefins with tethered alkyl halides and arylzinc reagents. The reaction shows an excellent functional group tolerance (such as ketones, esters, nitriles, and halides) and a moderate to good level of diastereoselectivity. The current cyclization/cross-coupling also tolerates molecules containing base-sensitive racemizable stereocenters, which are preserved without racemization during the reaction. This cyclization/cross-coupling provides a rapid access to (arylmethyl)carbo- and heterocyclic scaffolds, which occur widely as structural cores in various natural products and bioactive molecules. In order to show synthetic utility and generality, we have applied this new method in gram-scale quantities to the concise synthesis of six lignan natural products containing three different structural frameworks. We further conducted mechanistic investigations with radical probes and selectivity studies, which indicated that the current reaction proceeds via a single electron transfer (SET) process.
AB - We disclose a (terpy)NiBr2-catalyzed reaction protocol that regioselectively difunctionalizes unactivated olefins with tethered alkyl halides and arylzinc reagents. The reaction shows an excellent functional group tolerance (such as ketones, esters, nitriles, and halides) and a moderate to good level of diastereoselectivity. The current cyclization/cross-coupling also tolerates molecules containing base-sensitive racemizable stereocenters, which are preserved without racemization during the reaction. This cyclization/cross-coupling provides a rapid access to (arylmethyl)carbo- and heterocyclic scaffolds, which occur widely as structural cores in various natural products and bioactive molecules. In order to show synthetic utility and generality, we have applied this new method in gram-scale quantities to the concise synthesis of six lignan natural products containing three different structural frameworks. We further conducted mechanistic investigations with radical probes and selectivity studies, which indicated that the current reaction proceeds via a single electron transfer (SET) process.
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U2 - 10.1021/acs.joc.8b00184
DO - 10.1021/acs.joc.8b00184
M3 - Article
C2 - 29446941
AN - SCOPUS:85042872078
SN - 0022-3263
VL - 83
SP - 2920
EP - 2936
JO - Journal of Organic Chemistry
JF - Journal of Organic Chemistry
IS - 5
ER -