the a-amino radical 4 and the corresponding IrII
species 5. Given the established oxidation poten-
tial of prototypical amino acid carboxylate salts,
we expected this process to be thermodynami-
cally favorable [tert-butyl carbamoyl (Boc)–Pro-
OCs, E1/2red = +0.95 V versus SCE in CH3CN) (17).
Concurrently with this photoredox cycle, we
hoped that oxidative addition of the Ni(0) species
6 into an aryl halide would produce the Ni(II)
intermediate 7. We anticipated that this Ni(II)-aryl species would rapidly intercept the a-amino
radical 4, forming the organometallic Ni(III)
adduct 8. Subsequent reductive elimination
would forge the requisite C–C bond while delivering the desired a-amino arylation product 10
and expelling the Ni(I) intermediate 9. Last, SET
between the IrII species 5 and the Ni complex 9
would accomplish the exergonic reduction of
Ni(I) to Ni(0) {on the basis of the established two-electron reduction potential of Ni(II) to Ni(0), we
presume that reduction of Ni(I) to Ni(0) should
be thermodynamically favorable, E1/2red [NiII/Ni0] =
–1.2 V versus SCE in N,N´-dimethylformamide
(DMF)} by the IrII species 5 {E1/2red [IrIII/IrII] =
–1.37 V versus SCE in CH3CN} (22, 23), thereby
completing both the photoredox and the nickel
catalytic cycles simultaneously.
With this mechanistic hypothesis in hand, we
first examined the proposed coupling by using
N-Boc proline, para-iodotoluene, and a wide range
of photoredox and ligated nickel catalysts. To our
delight, we found that the combination of Ir[dF
(CF3)ppy]2(dtbbpy)PF6 and NiCl2•glyme (glycol
ether), dtbbpy, in the presence of 1.5 equivalents
of Cs2CO3 base and white light from a 26-W
compact fluorescent bulb, achieved the desired
fragment coupling in 78% yield. During our optimization studies, we found that use of a bench-stable Ni(II) source, such as NiCl2•glyme, was
sufficient to generate the arylation product with
comparable efficiency to a Ni(0) source. We attribute this result to in situ photocatalytic reduction of Ni(II) to Ni(0) via two discrete SET events,
with excess amino acid likely serving as the sacrificial reductant to access the active Ni catalyst
{E1/2red [NiII/Ni0] = –1.2 V versus SCE in DMF} (23).
We believe that it is unlikely that the Ni(II)(Ar)
X intermediate 7 undergoes a SET event to form
Ni(I)Ar, given the poorly matched reduction potentials of the species involved {compare with
E1/2red [NiIIArX/NiIAr] = –1.7 V versus SCE in
CH3CN and E1/2red [IrIII/IrII] = –1.37 V versus
SCE in CH3CN} (22, 24). However, we recognize
that an alternative pathway could be operable
wherein the oxidative addition step occurs from
the Ni(I) complex to form a Ni(III) aryl halide
adduct. In this pathway, photocatalyst-mediated
reduction of the aryl-Ni(III) salt to the corresponding Ni(II) species followed by the a-amino radical
addition step would then form the same productive Ni(III) adduct 8, as shown in Fig. 2. Given
that (i) Ni(0) complexes undergo oxidative addition more readily than Ni(I) complexes with aryl
halides (25) and (ii) Ni(II) complexes are believed
to rapidly engage with sp3 carbon-centered radicals
to form Ni(III) species (enabling sp3–sp2 and
sp3–sp3 C–C bond formations) (15, 16), we favor
the dual-catalysis mechanism outlined in Fig. 2.
Having established the optimal conditions
for this photoredox-nickel decarboxylative arylation, we focused our attention on the scope of
the aryl halide fragment. As shown in Fig. 3, a
wide range of aryl iodides are amenable to this
dual-catalysis strategy, including both electron-rich and electron-deficient arenes (10 to 13, 65
Fig. 4. Amino acid coupling partners and Csp3–H, C–X cross-coupling. (A) Evaluation of the amino
acid coupling partner in the decarboxylative-arylation protocol. Ac, acetyl group; LED, light-emitting
diode. (B) The direct Csp3–H, C–X cross-coupling via photoredox-nickel catalysis. All yields listed in Figs.
3 and 4 are isolated yields. Reaction conditions for (A) are the same as in Fig. 3. Reaction conditions for
(B) are as follows: photocatalyst 1 [1 mole (mol %)]; NiCl2·glyme (10 mol %), dtbbpy (15 mol %), KOH
(3 equiv.), DMF, 23°C, 26-W light. *Iodoarenes used as aryl halide, X = I. †Bromoarene used, X = Br.
