Letter
Photochemical Decarboxylative C(sp3)−X Coupling Facilitated by
Weak Interaction of N‑Heterocyclic Carbene
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ABSTRACT: While N-hydroxyphthalimide (NHPI) ester has
emerged as a powerful reagent as an alkyl radical source for a variety
of C−C bond formations, the corresponding C(sp3)−N bond
formation is still in its infancy. We demonstrate herein transition-
metal-free decarboxylative C(sp3)−X bond formation enabled by the
photochemical activity of the NHPI ester−NaI−NHC complex, giving
primary C(sp3)−(N)phth, secondary C(sp3)−I, or tertiary C(sp3)−
(meta C)phth coupling products. The primary C(sp3)−(N)phth
coupling offers convenient access to primary amines.
rimary amines make up an important class of compounds
example, Aggarwal and co-workers found that NHPI esters
could form the key heteroleptic ternary complex with a DMA
solvent molecule and bis(catecholato)diboron for the gen-
eration of alkyl radicals.4l Recently, Fu, Shang, and co-workers
developed the photocatalytic decarboxylative alkylations,
wherein the formation of a tricomponent EDA complex of
NHPI, NaI, and PPh3 was the key to their success.9 Drawing
inspiration from these elegant studies, we wondered whether
the EDA strategy could be used for decarboxylative carbon−
heteroatom bond formations, thus unleashing wider applica-
tions of NHPI esters through a new reactivity pattern.
The electrostatic interaction of an alkali-metal cation enables
the creation of new types of activation modes for a variety of
transformations.10 Specifically, N-heterocyclic carbenes
(NHCs),11 which have recently emerged as powerful catalysts
for photochemical transformations,12,13 could construct new
architectures with the alkali metal via weak electrostatic
interaction,14 which differs in comparison to those in
traditional NHC-catalyzed protocols that are reliant on the
formation of covalent bonds.15 Very recently, we found that
the weak electrostatic interaction of NHC and NaI could
facilitate the photochemical iodination of N-alkenoxypyridi-
nium salts.16 On the basis of the information presented above,
we envisioned that an alternative approach could be devised
for the formation of the photon-absorbing EDA complex
among NHPI esters, NHC, and NaI. Specifically, we expected
that, after cross-coupling of the alkyl radical and iodine radical
P
in biological and synthetic chemistry that are featured in
various pharmaceuticals.1 They can be prepared by traditional
approaches such as Gabriel reaction, Curtius rearrangement,
2
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Schmidt reaction, and Delepine reaction (Scheme 1A).
However, considering the issues of safety, material sourcing,
and reagent cost associated with these methods, and green
trends in modern synthetic chemistry, there is a great demand
to address these problems as much as possible. In the recent
decade, functional group transfer radical reactions have proven
to be a powerful tool for the construction of synthetically
important bonds. With the development of first-row transition-
metal catalysis, photoredox catalysis, and electrochemistry, N-
hydroxyphthalimide (NHPI) ester that can be readily prepared
from ideal feedstock chemicals (i.e., carboxylic acids) has
emerged as a powerful functional group transfer reagent for the
generation of the alkyl radical in a variety of cross-couplings
(Scheme 1B).3 However, compared with the great progress in
the construction of carbon−carbon bonds, carbon−heteroa-
tom bond formations with the reagent are still in their infancy.4
In this context, the N-alkyl bond forming reaction is
particularly significant and continues to be a challenge at the
forefront of synthetic chemistry.4g,5 In 2017, Fu, Peters, and
co-workers reported a photoinduced, copper-catalyzed decar-
boxylative C(sp3)−N coupling of NHPI esters, which offers a
valuable alternative to the traditional Curtius rearrangement
for preparing protected amines.6 Further efforts by the Hu
group resulted in a dual copper/photoredox catalysis for the
cross-couplings of NHPI esters and benzophenone imines or
anilines for the synthesis of alkyl amines and anilines (Scheme
1C).7
Received: September 8, 2020
Recent interest in the photoactive electron donor−acceptor
(EDA) complex has led to numerous advances for the
generation of a wide range of synthetically important radicals,
providing new possibilities of utilizing NHPI esters.8 For
© XXXX American Chemical Society
Org. Lett. XXXX, XXX, XXX−XXX
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