Chapter 5. Development of photoinduced, copper-mediated and copper-catalyzed C- N coupling reactions N coupling reactions
5.2 Results and discussion
5.2.1 Stoichiometric C aryl -N coupling reactivity
During the past several years, we have explored the chemistry of copper(I) amido complexes,17-18 and we have determined that adducts such as carbazolide complex (Ph3P)2Cu(carbazolide) (5.2) are photoluminescent.19 We envisioned that we could capitalize on the photophysical properties of this family of complexes as a mechanistic tool to examine the viability of an SET/radical pathway for Ullmann C–N bond formation (Fig. 5.2). Thus, photolysis of a copper–carbazolide complex could lead to electron
transfer to the aryl halide to afford a radical anion, which would rapidly fragment to form an aryl radical and a halide anion (top of Fig. 5.2).20 This aryl radical could then react with the copper complex to furnish the C–N coupling product. Alternatively, the aryl radical could be generated directly through halogen atom transfer from the aryl halide to the excited copper–carbazolide complex (inner-sphere electron-transfer; bottom of Fig.
5.2). Regardless of which pathway is followed, this would represent, to our knowledge, the first example of a photoinduced Ullmann coupling to form a C–N bond.
Figure 5.2 Outline of a possible pathway for photoinduced Ullmann C–N bond formation via a copper–carbazolide complex.
In a preliminary investigation, photolysis of PPh3 adduct 5.2 in the presence of iodobenzene did indeed result in C–N bond formation; however, the solubility properties of complex 5.2 led us to synthesize a new, related copper complex wherein the PPh3
ligands are replaced with P(m-tol)3. A single-crystal X-ray diffraction study confirmed that the copper–carbazolide complex 5.1 maintains a three-coordinate trigonal-planar geometry in the solid state (Fig. 5.3). Complex 5.1 is colorless and is not visibly luminescent in acetonitrile; however, emission and excitation spectra confirm that it has accessible excitations available in the near ultraviolet (Fig. 5.4A).
Figure 5.3. X-ray structure of copper complex 5.1 (thermal ellipsoids drawn at 50%
probability).
When a solution of copper–carbazolide complex 1 and iodobenzene in CH3CN is irradiated with a standard 13-watt compact fluorescent light bulb (CFL) at room temperature for 10 hours, C–N bond formation proceeds in good yield (77%; Table 1, entry 1); an even higher yield is obtained in CD3CN (84%; entry 2). Under otherwise identical conditions in the absence of light, no N-phenylcarbazole is observed (<1%;
entry 3), and negligible coupling occurs in the dark even upon heating at 65 °C for 12 hours. Finally, irradiation of a mixture of carbazole and iodobenzene (without 1) leads to no detectable N-phenylcarbazole (<1%).
Figure 5.4. (A) Emission and excitation spectra of copper complex 5.1 in CH3CN. (B) Chemical oxidation of copper complex 5.1.
Photolysis of a solution of copper–carbazolide complex 5.1 and iodobenzene with a 100-watt mercury lamp results in C–N bond formation even at –40 oC (Table 5.1, entry 4). This observation is noteworthy because previously described couplings of carbazole with iodobenzene in the presence of copper have employed temperatures of at least 90
°C.21
Table 5.1. Photoinduced Ullmann C–N coupling reactions of copper–carbazolide complex 5.1 with PhX (X = I, Br, Cl).
Coupling with iodobenzene (X = I)
Entry Conditions Yield
(%)a
1 standard conditions 77 (74)
2 CD3CN instead of CH3CN 84 (82)
3 dark <1
4 –40 °C, 100-watt Hg lamp 69 (68)
Coupling with bromobenzene (X = Br)
Entry Conditions Yield
(%)a
5 standard conditions 40
6 100-watt Hg lamp 76 (72)
7 –40 °C, 100-watt Hg lamp, 5 equiv PhBr 59
8 dark <1
Coupling with chlorobenzene (X = Cl)
Entry Conditions Yield
(%)a
9 standard conditions 5
10 100-watt Hg lamp, 24 h, 5 equiv PhCl 68 (66) 11 –40 °C, 100-watt Hg lamp, 5 equiv PhCl 11
12 dark <1
a Yields were determined by GC analysis versus a calibrated internal standard (4,4’-di-t-butylbiphenyl) and are the average of at least two experiments; yields of purified product are in parentheses.
For these photoinduced Ullmann C–N coupling reactions, we postulate that upon irradiation an excited state of copper complex 5.1 transfers an electron to iodobenzene to
produce a radical ion pair (Fig. 5.2). The higher yield obtained in CD3CN (Table 5.1, entry 2) compared with CH3CN (entry 1) can be attributed to a kinetic isotope effect for undesired abstraction of a hydrogen/deuterium from the solvent by the phenyl radical or by radical cation 5.3 (Fig. 5.2). Consistent with this hypothesis, we observe benzene and unsubstituted NH carbazole as side products in these photoinduced couplings, and we have established that, when we independently generate radical cation 5.3 via chemical oxidation of 5.1 in CH3CN, the unsubstituted NH carbazole is formed (Fig. 5.4B).22
Bromobenzene also undergoes Ullmann coupling when irradiated with a 13-watt CFL in the presence of copper–carbazolide complex 5.1. As would be expected on the basis of relative reduction potentials (PhI: –1.91 V; PhBr: –2.43 V; PhCl: –2.76 V (vs. SCE in DMF on a platinum electrode)),23 photoinduced C–N bond formation is considerably slower for bromobenzene (Table 5.1, entry 5) than for iodobenzene (entry 1).
Nevertheless, a good yield of the desired product can be obtained at room temperature if a 100-watt mercury lamp is used (entry 6), and a moderate yield is observed even at –40
°C (entry 7). In the absence of light, no Ullmann coupling occurs (entry 8).
We are not aware of previous reports of Ullmann couplings of carbazole with chlorobenzene. We estimate the excited-state reduction potential of copper–carbazolide complex 5.1 to be ~ –2.6 V (vs. SCE in CH3CN; based on the electrochemistry of 5.1 and its approximate value of E00 = 3.1 eV (obtained from the intersection of the emission and excitation profiles of 5.1)), which suggests that electron transfer to chlorobenzene is viable. Under the standard conditions for the reaction of copper–carbazolide complex 5.1 with iodobenzene, chlorobenzene undergoes cross-coupling in low yield (5%; Table 5.1, entry 9). However, irradiation by a 100-watt mercury lamp in the presence of excess
chlorobenzene leads to efficient photoinduced Ullmann coupling at room temperature (entry 10).