The development of readily tunable
and regioselective C–H
functionalization reactions that operate solely through catalyst control
remains a challenge in modern organic synthesis. Herein, we report
that simple silver catalysts supported by common nitrogenated ligands
can be used to tune a nitrene transfer reaction between two different
types of C–H bonds. The results reported herein represent the
first example of ligand-controlled and site-selective silver-promoted
C–H amination.
The development of new catalysts for selective nitrene transfer is a continuing area of interest. In particular, the ability to control the chemoselectivity of intermolecular reactions in the presence of multiple reactive sites has been a long-standing challenge in the field. In this paper, we demonstrate examples of silver-catalyzed, nondirected, intermolecular nitrene transfer reactions that are both chemoselective and flexible for aziridination or C‒H insertion, depending on the choice of ligand. Experimental probes present a puzzling picture of the mechanistic details of the pathways mediated by [(tBu3tpy)AgOTf]2 and (tpa)AgOTf. Computational studies elucidate these subtleties and provide guidance for the future development of new catalysts exhibiting improved tunability in group transfer reactions.
The discovery of transition metal complexes capable of promoting general, catalyst-controlled and selective carbon-hydrogen (C-H) bond amination of activated secondary C-H bonds over tertiary alkyl C(sp(3))-H bonds is challenging, as substrate control often dominates when reactive nitrene intermediates are involved. In this letter, we report the design of a new silver complex, [(Py5Me2)AgOTf]2, that displays general and good-to-excellent selectivity for nitrene insertion into propargylic, benzylic, and allylic C-H bonds over tertiary alkyl C(sp(3))-H bonds.
An array of silver complexes supported by nitrogen-donor ligands catalyze the transformation of C═C and C-H bonds to valuable C-N bonds via nitrene transfer. The ability to achieve high chemoselectivity and site selectivity in an amination event requires an understanding of both the solid- and solution-state behavior of these catalysts. X-ray structural characterizations were helpful in determining ligand features that promote the formation of monomeric versus dimeric complexes. Variable-temperature H and DOSY NMR experiments were especially useful for understanding how the ligand identity influences the nuclearity, coordination number, and fluxional behavior of silver(I) complexes in solution. These insights are valuable for developing improved ligand designs.
Protein
immobilization techniques on polymeric supports have enabled
many applications in biotechnology and materials science. Attaching
the proteins with controlled orientations has inherent advantages,
but approaches for doing this have been largely limited to cysteine
or noncanonical amino acid targeting. Herein, we report a method to
attach the N-terminal positions of native proteins to polymer resins
site-specifically through the use of 2-pyridinecarboxyaldehyde (2PCA)
derivatives. For high protein loadings and practical synthesis, we
initiated this work by preparing highly reactive 2PCA derivatives
using Pd-catalyzed cross-coupling amination. The resulting compounds
were attached to amine-containing polyethylene glycol acrylamide resin
(PEGA-NH2), which subsequently reacted with the N-termini
of proteins to produce linkages that were stable over the long term
but could be reversed through the addition of hydroxylamine. We envision
that this site-selective, 2PCA-based protein immobilization can provide
a simple and generalizable immobilization protocol.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.