TY - JOUR
T1 - Chemoselectivity for Alkene Cleavage by Palladium-Catalyzed Intramolecular Diazo Group Transfer from Azide to Alkene
AU - Frost, Grant B
AU - Mittelstaedt, Michaela N.
AU - Douglas, Christopher J
N1 - Publisher Copyright:
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2019/2/1
Y1 - 2019/2/1
N2 - Alkenes can be cleaved by means of the (3+2) cycloaddition and subsequent cycloreversion of 1,3-dipoles, classically ozone (O 3 ), but the azide (R−N 3 ) variant is rare. Chemoselectivity for these azide to alkene diazo group transfers (DGT) is typically disfavored, thus limiting their synthetic utility. Herein, this work discloses a palladium-catalyzed intramolecular azide to alkene DGT, which grants chemoselectivity over competing aziridination. The data support a catalytic cycloreversion mechanism distinct from other known metal-catalyzed azide/alkene reactions: nitrenoid/metalloradical and (3+2) cycloadditions. Kinetics experiments reveal an unusual mechanistic profile in which the catalyst is not operative during the rate-controlling step, rather, it is active during the product-determining step. Catalytic DGT was used to synthesize N-heterocyclic quinazolinones, a medicinally relevant structural core. We also report on the competing aziridination and subsequent ring expansion to another N-heterocyclic core structure of interest, benzodiazepinones.
AB - Alkenes can be cleaved by means of the (3+2) cycloaddition and subsequent cycloreversion of 1,3-dipoles, classically ozone (O 3 ), but the azide (R−N 3 ) variant is rare. Chemoselectivity for these azide to alkene diazo group transfers (DGT) is typically disfavored, thus limiting their synthetic utility. Herein, this work discloses a palladium-catalyzed intramolecular azide to alkene DGT, which grants chemoselectivity over competing aziridination. The data support a catalytic cycloreversion mechanism distinct from other known metal-catalyzed azide/alkene reactions: nitrenoid/metalloradical and (3+2) cycloadditions. Kinetics experiments reveal an unusual mechanistic profile in which the catalyst is not operative during the rate-controlling step, rather, it is active during the product-determining step. Catalytic DGT was used to synthesize N-heterocyclic quinazolinones, a medicinally relevant structural core. We also report on the competing aziridination and subsequent ring expansion to another N-heterocyclic core structure of interest, benzodiazepinones.
KW - alkene cleavage
KW - azides
KW - cycloreversion
KW - diazo group transfer
KW - palladium
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U2 - 10.1002/chem.201805904
DO - 10.1002/chem.201805904
M3 - Article
C2 - 30512211
AN - SCOPUS:85059515641
SN - 0947-6539
VL - 25
SP - 1727
EP - 1732
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
IS - 7
ER -