ACS Catalysis
Letter
Scheme 1. Strategies for Deaminative Functionalizations
with N-Alkylpyridinium Salts
A survey of various Ni-based salts, ligands, electron donors,
and solvents was performed to merge pyridinium salt 5 with
We then found that the desired deaminative arylation product
8
was obtained in 85% isolated yield within 16 h, using 10
mol % of NiBr ·diglyme and 11 mol % of bipyridine L1 in the
2
presence of Hantzsch ester 7 as a reductant and DMA as a
solvent (see Scheme 2a). Replacing the Ni complex, ligand, or
solvent with other alternatives led to lower yields, and no
product was detected in the absence of the catalyst, 7 or light
(
see the SI for details). Reaction conditions were separately
with alkyl iodide 10 (see the SI for details), and 20 mol % of
the Ni-based complex derived from NiBr ·diglyme and L2 was
2
revealed to be optimal to furnish 12 in 76% isolated yield (83%
GC yield; see Scheme 2b). Decreasing the catalyst loading to
10 mol % resulted in diminished efficiency (62% GC yield).
Remarkably, performing the alkylation using a 1:1 ratio of 9
and 10 delivered 12 with a respectable GC yield of 55% (see
the SI for details). This compares favorably with other
reductive cross-electrophile protocols that employ super-
stoichiometric quantities of one cross-partner (2−3 equiv) to
8
c
suppress adventitious homocoupling, or entail strongly
7d,14b
5g
basic
and cryogenic conditions. Note that the analogous
alkylation with bromoalkane 11, in the presence of
tetrabutylammonium iodide (TBAI) as an additive, could
also generate 12 in 47% yield.
With the established conditions in hand, we first examined
the scope of deaminative arylation using a diverse array of
pyridinium salts 1 (secondary and primary alkyl, cyclic, and
acyclic) as well as bromoarenes 2 (see Scheme 3). Generally,
various electronically modified aryl bromides served as
effective substrates in cross-coupling, affording products in
up to 92% yield. These include molecules containing a nitrile
Catalyzed Deaminative Arylation and Alkylation
a
(
13), an alcohol (36), an aldehyde (14), a ketone (15, 20), an
ester (19, 21, 25, 29), an amide (18, 27, 32−36), a sulfone
16) and a sulfoamide (17, 39, 40, 43). Synthesis of Lewis
(
basic heterocycle 28, as well as products derived from
multifunctional bioactive compounds (22−24, 37, 38, 41,
4
2) further underscores the exceptional functional group
compatibility of the photoinduced catalytic reaction system.
Benzylpyridinium salts are also amenable substrates, although
purple light irradiation was required to give the product (43).
Reactions with functionalized aliphatic iodides were sub-
sequently investigated (see Scheme 4). Deaminative alkylation
was found to proceed efficiently to deliver 44−57 in up to 73%
yield. Commonly occurring functional groups such as a
phthalimide (44, 46, 47, 53, 54), an amino ester (49), an
ether (55) as well as an electron-deficient enoate (45, 56) are
tolerated. Chemoselective cross-coupling with the iodoalkane
motif enables access to 48, which bears a reactive aryl bromide
handle that could be subjected to further transformations.
Similar to the processes in Scheme 3, deaminative alkylation
with substrates appended to complex molecules could be
effected to generate the corresponding products 50−52. Of
particular note, the formation of 57 demonstrates a key
advantage of the present photoinduced catalytic manifold,
since alkyl-substituted aldehydes are found to be sensitive
a
Yields are for isolated and purified products.
orthogonal activation of 1 and 2 means that difficult alkyl−
alkyl cross-coupling reactions that are often susceptible to
competitive homocoupling
under mild base-free conditions at ambient temperature
without an exorbitantly large excess of either reactant, thereby
reducing waste generation. Herein, we describe the successful
implementation of a photoinduced deaminative strategy to
facilitate C(sp )−C(sp ) and C(sp )−C(sp ) cross-electro-
phile coupling with readily available organohalides.
4b,19
side pathways can be achieved
8b,d
toward excess metallic reductants
(see the SI for details).
Formation of photoactive EDA complexes between N-
alkylpyridinium salts 1 and 7 have already been documented in
2
3
3
3
18
previous studies. Further control experiments were per-
6
520
ACS Catal. 2021, 11, 6519−6525