A Hypervalent Iodide-Initiated Fragment Coupling Cascade of N-Allylhydrazones

摘要

Reliable bond-forming reactions that enable the union of two or more molecular fragments are essential for the efficient and convergent assembly of complex natural products or medicinal agents. As part of a program aimed at developing such reactions, we have been investigating the utility of N-allylhydrazides as versatile chemical intermediates that allow for high yielding fragment coupling by way of hydrazone formation followed by a carbon-carbon bond-forming molecular rearrangement.Most recently, we reported a triflimide-catalyzed rearrangement of N-allylhydrazones (the Stevens [3,3] rearrangement) that allows for a "traceless" bond construction between two fragments. Prior to this development, we reported an N-bromosuccinimide (NBS)-initiated rearrangement that not only allowed for such fragment assembly but also incorporated an additional bromide atom (i.e., 1→4, Nuc = Br). We speculated that N-bromination, followed by loss of bromide, initiated the cascade sequence through diazoallene species 2 (Scheme 1). A [3,3] sigmatropic rearrangement would afford diazonium ion 3, which would react with bromide to produce the benzylic bromide 4 (Nuc = Br).