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Chemoselectivity for Alkene Cleavage by Palladium‐Catalyzed Intramolecular Diazo Group Transfer from Azide to Alkene
Author(s) -
Frost Grant B.,
Mittelstaedt Michaela N.,
Douglas Christopher J.
Publication year - 2019
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201805904
Subject(s) - alkene , chemoselectivity , chemistry , diazo , azide , intramolecular force , palladium , catalysis , cycloaddition , combinatorial chemistry , photochemistry , medicinal chemistry , stereochemistry , organic chemistry
Abstract 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.