Deoxygenative cross-electrophile coupling of benzyl chloroformates with aryl iodides

Article abstract of DOI:10.1039/c9ob00628a

This work describes Ni-catalyzed cross-electrophile coupling of benzyl chloroformate derivatives with aryl iodides that generates a wide range of diaryl methane products. The mild reaction conditions merit the C-O bond radical fragmentation of benzyl chloroformates via halide abstraction or a single electron reduction by a Ni catalyst. This work offers a new substrate type for cross-electrophile couplings.

Full text of DOI:10.1039/c9ob00628a

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Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
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DOI: 10.1039/C9OB00628A
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Deoxygenative Cross-Electrophile Coupling of Benzyl
Chloroformates with Aryl Iodides
Yingying Pan,† Yuxin Gong,† Yanhong Song, Weiqi Tong and Hegui Gong*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
alkyl halides that generates C(sp3)–C(sp3) bonds, which likely involves
oxidative addition of benzyl C–O bonds to Ni(0).11 Such a process
differs from our recent Zn-mediated tertiary C-O bond scission.13-14
This work describes Ni-catalyzed cross-electrophile of benzyl
chloroformate derivatives with aryl iodides that generates a wide
range of diaryl methane products. The mild reaction conditions
merit C–O bond radical fragmentation of benzyl chloroformates via
halide abstraction or a single electron reduction by Ni catalyst. This
work offers a new substrate type for cross-electrophile couplings.
We envisaged that activation of benzyl alcohols with chlorocarbonyl
may allow C–O bond scission via halide abstraction or one electron
reduction followed by decarboxylation. Further reaction of the
resultant benzyl radicals with Ar–Ni(II) intermediates under the Ni-
catalyzed reductive coupling conditions may enable the formation of
benzyl C(sp3)–C(sp2) products. Herein, we report our discovery of Ni-
catalyzed reductive coupling of benzyl chloroformates with aryl
iodides that generates diaryl methane products. The mild reaction
conditions are compatible with secondary benzylic derivatives and
tolerate a wide range of functional groups such as aldehydes.
Use of benzyl alcohol and its derivatives as the coupling partners has
spurred considerable interests in the field of C–C bond forming
chemistry.1 Among various transition metal catalyzed benzyl C–O
bond couplings, the earth abundant nickel has been widely adopted.
Notable protocols include Jarvo’s benzyl ether coupling with
organometallic reagents,2 Shi’s Kumada and Suzuki process (Scheme
1).3 These elegant methods are compatible with naphathyl-,
benzofuanyl-, benzo[b]thiophenyl-, and furylmethylenyl C–O
bonds.2-3 The reactions appear to take advantages of arene-assisted
C–O bond oxidative addition to low valent Ni.2-3 On the other hand,
benzyl C–O bonds has been intensively used in Ni-catalyzed cross-
electrophile couplings.4-11 In this context, generation of benzyl
radicals are often involved. Whereas Weix utilized Co,4 Ukaji
employed Ti as the reducing reagent to unlock the C–O bond
homolytically to create benzyl radical.5 The benefits of using benzyl
alcohol and its derivatives over benzyl halides is obvious,12 as the
latter are generally reactive on benchtop, and need to store with
care. This is even true for benzyl tosylates and mesylates.4 However,
the concurrent benzyl C–O bond activation/coupling methods are
generally limited to primary alcohols or diaryl methanols,4-11 unlike
their halide counterparts which are suitable for alkyl-substituted
secondary benzyl substrates. More recently, Shu has developed a Ni-
catalyzed cross-electrophile coupling of primary benzyl oxalates with
†Center for Supramolecular Chemistry and Catalysis and Department of
Chemistry, Shanghai University, 99 Shang-Da Road, Shanghai 200444, China.
hegui_gong@shu.edu.cn
† Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000
Scheme 1. Ni-catalyzed cross-electrophile arylation of benzyl C–O
bonds.
We commenced our studies with the reaction of
chlorobenzylformate with 4-iodoanisole, by setting the latter as the
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c
1
limiting reagent.15 After extensive investigations, we identified that
a combination of Ni(acac)2 (10 mol%) with L4 in the presence of
MgBr2 (1.0 equiv) at 40 ℃, gave 1a with an excellent yield 96%,
wherein DMA was used as the solvent and Zn as the reductant (Table
1, entry1). Variation of the temperatures did not result in a better
yield (entries 2–3). Reducing the amount of chloroformates to 1.2
equiv did not lead to appreciable reduction of yield, whereas use of
1 equiv of chloroformate only generated 1a in 74% yield (entries 4–
5). Exploration of other ligands (entries 6–11), salt additives (e.g.,
MgCl2 and LiCl, entries 12–13) and solvents (14–15) were not
satisfactory. Control experiments indicated that only Ni was
indispensable; without MgBr2, 1a was obtained in 53% yield (entries
16–18). Finally, use of 4-chloro and 4-boromo anisoles to replace the
4-iodo counterpart was not effective (entries 19–20). We reason that
MgBr2 may serve to activate Zn surface. In addition, a possible halide
exchange between Cl and Br may take place, as MgCl2 appears to be
less important (Table 1, entry 12 vs 18). This may accelerate the
reduction of chloroformates since bromide is a better leaving group.
reference. Isolated yield. d Not detected by H NMVRie.wDAMrtiAcle=Online
DOI: 10.1039/C9OB00628A
N,N-dimethylacetamide, acac = acetylacetonate. Nd = not
detected.
With the optimized reaction conditions in hand, we examined the sc
ope and limitations of primary benzyl chloroformates and aryl iodid
es (Figure 1). The reaction was effective for aryl iodide substituted w
ith electron-withdrawing groups as exemplified by 1b–1e. The use o
f methyl 4-bromobenzoate delivered 1b in 83% yield, whereas prep
aration of 1b on a 1 mmol scale was obtained in 76% yield. The subs
titution patterns of the aryl iodides were not important for the coup
ling efficiency (e.g., 1f and 1g vs 1a). Other aryl iodides including 1-n
aphthyl, 1-pyrenyl, benzo[b]thiophenyl and benzofuryl were all suita
ble, as evident in 1h–1n. Chloroformates bearing electron-withdraw
ing and electron-donating groups at the benzene rings all gave excel
lent coupling yields for 2a–7a.
Table1. Optimization of the reaction conditions for the coupling of
benzyl chloroformate with 4-iodoanisole.
entrya
variation from the "standard
conditions"
yield%b
1
2
3
none
96 (95)c
89
86
50 oC
25 oC
4
5
6
1.2 equiv of benzyl chloroformate
1.0 equiv of benzyl chloroformate
L5 instead of L4
92
74
75
7
8
9
L2 instead of L4
pyridine instead of L4
L1 instead of L4
72
70
42
Figure 1. Coupling of primary chloroformates and aryl iodides using
the standard method as in Table 1, entry 1.
We next turned out attention to the secondary benzyl
10
11
12
13
14
15
16
17
18
19
20
L3 instead of L4
L6 instead of L4
94
23
60
trace
60
43
nd
18
53
MgCl2 instead of MgBr2, 50 oC
LiBr instead of MgBr2, 50 oC
CH3CN instead of DMA
THF instead of DMA
w/o Ni(acac)2
chloroformates (Figure 2). Under the standard reaction conditions
(Table 1, entry 1), the coupling of chloroformate derived from
phenyl-1-ethanol with methyl 4-iodobenzoate only resulted in 8a in
63% yield. Gratifyingly, the yield was boosted to 86% by replacement
of Ni(acac)2 with NiCl2(DME). With these modified conditions, the
substrate compatibility was investigated as exemplified by 8a–19a.
Whereas 3-iodobenzoate was inferior to the 4-iodo counterpart, 2-
iodobenzoate only resulted in 8c in a trace amount. The reaction was
also effective for electron-rich arenes, as manifested by 8d. The mild
reaction conditions were tolerant of a wide range of functional
groups. These comprised aldehyde, fluoro, chloro and cyano groups.
Installation of different substituents into the benzene rings of the
w/o L4
w/o MgBr2
4-chloroanisole instead of 4-iodoanisole nd
4-bromoanisole instead of 4-
iodoanisole
<10
a Reaction conditions: benzyl chloroformate (1.5 equiv), aryl
iodide (0.3 mmol, 1.0 equiv), Zn (2.0 equiv), L4 (15 mol%),
Ni(acac)2 (10 mol%), and MgBr2 (1.0 equiv) in DMA (1 mL) at 40
℃ for 12h. b NMR yield using 2,5-dimethylfuran as the internal
2 | J. Name., 2012, 00, 1-3
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chloroformates were generally effective, as evidenced by examples one molecule of carbon dioxide produced a benzyl radical, which can
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DOI: 10.1039/C9OB00628A
of 9a–17a. Increase the size of the alkyl groups at the benzylic carbon be intercepted by an in situ formed aryl–Ni(II) species to give aryl-
with respect to methyl reduced the coupling efficiency, wherein 18a– Ni(III)-Bn intermediate. Reductive elimination of the putative Ni(III)
18b were obtained in moderate yields. Finally, chloroformate species gave the coupling product.17 This hypothesis was verified by
derived from 2,3-dihydro-1H-inden-1-ol also afforded 19a in 78% an equimolar reaction of benzyl chloroformate with an aryl-Ni(II)
yield.
intermediate 22 obtained by oxidative addition of methyl 4-
iodobenzoate with L3–Ni(0) (eq 3).18 We obtained 1b in 38% and 30%
yields with or without MgBr2 (eq 2), suggesting that Ni(II) may
abstract the chlorine, and result in benzyl radical by release of CO2.
Addition of Zn in Eq 3 improved the yield to 58%, suggesting that Zn
promotes the reaction. In addition, the reaction of 20 and 22 gave 21
in 33% yield, conforming that alkyl radical is involved.
Figure 2. Coupling of secondary chloroformates and aryl iodides. The
reaction was conducted using the standard method in Table 1, entry
1, except that NiCl2(glyme) was used in place of Ni(acac)2.
In summary, we have disclosed that benzyl chloroformates were
suitable for radical C–O bond fragmentation and subsequent
coupling with aryl–Ni intermediates under Ni-catalyzed reductive
coupling conditions. The reaction conditions tolerate a wide arrange
of substrates and functional groups. The mild and easy-to-operate
method adds a new entry to the construction of diaryl methane
products, which is complementary to the concurrent cross-
electrophile coupling of benzyl C–O bonds.
We also briefly investigated whether unactivated alcohol decorated
with chloroformate would be adapted to the reaction conditions. As
shown in equation 1, cyclopentyl substrate performed best; both
electron-rich and deficient aryl iodides were suitable. However
cyclohexyl and isopropyl substrates were not effective, suggesting
that the nature of unactivated alkyl groups differs from that of benzyl
one.
Acknowledgement
Financial support was provided by the Chinese NSF (Nos. 21871173
and 21572127).
Notes and references
† These authors contribute equally
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DOI: 10.1039/C9OB00628A
Deoxygenative Cross-Electrophile Coupling of Benzyl Chloroformates
with Aryl Iodides
Yingying pan,† Yuxin Gong,† Yanhong Song, Weiqi Tong and Hegui Gong*
†Center for Supramolecular Chemistry and Catalysis and Department of Chemistry, Shanghai University,
99 Shang-Da Road, Shanghai 200444, China
E-mail: Hegui_Gong@shu.edu.cn
We disclose herein a Ni-catalyzed benzyl C-O bond radical fragmentation/cross-
electrophile coupling of benzyl chloroformates with aryl iodides to generate diaryl
methane derivatives.
TOC:
R
I
R
O
Ni (cat.)/Bipy
Zn, DMA
R'
Ar
Ar
O
Cl
R'
- C-O bond radical fragmentation
- mild reaction conditions