Ni-catalyzed reductive coupling of α-halocarbonyl derivatives with vinyl bromides

Article abstract of DOI:10.1039/c6ob02269c

This work describes the vinylation of α-halo carbonyl compounds with vinyl bromides under Ni-catalyzed reductive coupling conditions. While aryl-conjugated vinyl bromides entail pyridine as the sole labile ligand, the alkyl-substituted vinyl bromides require both bipyridine and pyridine as the co-ligands.

Full text of DOI:10.1039/c6ob02269c

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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/C6OB02269C
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Ni-Catalyzed Reductive Coupling of α-Halocarbonyl Derivatives
with Vinyl Bromides
Canbin Qiu,a Ken Yao a,* Xinhua Zhangb,* and Hegui Gonga,*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
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Herein, we demonstrate that preparation of 3-enoates and 3-
enamides can be readily accomplished from cross-electrophile
coupling of the vinyl and a-halo carbonyl derivatives (Scheme 1). For
aryl-conjugated vinyl halides, pyridine was used as the sole ligand,
whereas for alkyl-decorated vinyl halides, co-existence of pyridine
and bipyridine was necessary for the vinylation process.
This work describes vinylation of α-halo carbonyl compounds with
vinyl bromides under Ni-catalyzed reductive coupling conditions.
While aryl-conjugated vinyl bromides entails pyridine as the sole
labile ligand, the alkyl-substituted vinyl bromides requires both
bipyridine and pyridine as the co-ligands.
Carbonyl compounds bearing α-vinyl groups are important organic
synthons and some are bioactive.1-2 They are generally prepared via
transition metal-catalyzed α-alkenylation of carbonyl compounds.3-5
In this context, Pd and Ni-catalyzed vinylation of enolates with vinyl
electrophiles has received much attention.3-4 The oxidative coupling
of enolates with vinyl-boron reagents should also be noted.5 On the
other hand, the Ni- and Pd-catalyzed coupling of vinyl- metallic
reagents with α-halocarbonyl compounds represents a different
strategy, wherein asymmetric methods have also been achieved
(Scheme 1).6
Scheme 1. Vinylation of α-carbonyl compounds
In contrast, the construction of the vinyl–alkyl C–C bonds from
unactivated alkyl halides with vinyl halides has been explored using
Ni-, Pd- as well as photo-redox/Ni-catalyzed reductive protocols,7-10
wherein excellent chemoselectivity featuring equimolar loading of
the coupling partners has been succeeded using Ni/bipy-catalytic
conditions.7b However, vinylation of α-carbonyl compounds has only
been disclosed using an electrochemical reductive coupling
method,11 although the equivalent arylation methods have been
dislosed.12-13 Therefore, development of parallel chemical reductive
conditions is needed for practical reasons. Noteworthy is that the
activated alkyl halides such as α-halocarbonyl derivatives generally
display distinct reactivity from the unactivated counterparts.
Dimerization and hydrodehalogenation side reactions may become
problematic for substrates of these types.14-15 Hence, exploration of
reductive coupling methods based on α-halocarbonyl derivatives is
nontrivial.
We have determined that the reaction of ethyl 2-
chloropropanoate 1a with (2-bromovinyl)benzene 2 (E/Z = 84/16)
afforded 3 in an optimal yield of 88% with an E/Z ratio of 90:10,
wherein 1 equiv of pyridine was the only labile ligand (Table 1, entry
1).16 The addition of 2,2’-bipyridine (30 mol %) eroded the reaction
yield to 70%, which is pivotal for the analogous electrochemical
method.11 We also identified that readily available Ni(ClO4)2·6H2O
was comparably effective (entry 2), while NiBr2 was inferior (entry 3).
Use of 5 mol % Ni catalyst resulted in 3 in 78% yield with slightly
enhanced E selectivity (entry 4). Lowering the loading of 2 to 1.5
equivalents also afforded 3 in good yield (entry 5). Changes of other
parameters such as solvents, reductants, temperatures did not result
in better outcomes (entries 6–9). Utilization of E-vinyl bromides only
led to E-product, whereas isomerization of the pure Z-vinyl substrate
was detect, which gave an E/Z ratio of 16/84 (entries 10–11). The
reason for partial isomerization of the Z-vinyl groups under the
Ni/Mn conditions is not clear at this time.17 Finally, the bromo analog
of 1 also generated 3 in equally good yield when MgCl2 was added
(entries 12–13).
a Center for Supramolecular Chemistry and Catalysis, and Department of
Chemistry, Shanghai University, 99 Shang-Da Road, Shanghai 200444, China
b College of Chemical and Environmental Engineering, Shanghai University of
Technology, 100 Hai-Quan Road, Shanghai 201418, China.
*Hegui_gong@shu.edu.cn; yao850618jp@yahoo.co.jp; zxhxmu@126.com.
†Electronic Supplementary Information (ESI) available: [details of any
supplementary information available should be included here]. See
DOI: 10.1039/x0xx00000x
Table 1. Optimization for the coupling of 1 and 2.a,b
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E/Z ratios were obtained by GC. f The bromo carbonyl substrate was used with
addition of 1 equiv of MgCl2.
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DOI: 10.1039/C6OB02269C
Table 3. Substrate scope for the alkyl-substituted vinyl
bromides.a,b,c
Entry
Variations
conditions
from
standard yield% (E/Z)c
1
none
88 (90/10)
2
Ni(ClO4)2·6H2O instead of Ni(COD)2
NiBr2 instead of Ni(COD)2
5 mol % of Ni(COD)2
82 (92/8)
52 (93/7)
78 (94/6)
72 (94/6)
68 (94/6)
77 (95/5)
60 (95/5)
62 94/6)
3
4
5
1.5 equiv of 2 instead of 2 equiv
Zn instead of Mn
6
7
DMAP instead of pyridine
DMF instand of DMA
40 oC instand of 25 oC
E-2 (E/Z > 99:1)
8
9
10
11
12
88 (>99:1)
70 (16/84)
Z-2 (E/Z <99:1)
ethyl 2-bromopropanoate instead 68 (95/5)
of 1
13
ethyl 2-bromopropanoate instead 86 (90/10)
of 1, with 1 equiv of MgCl2
a Standard conditions: 1a (0.15 mmol), 2 (0.3 mmol, E/Z = 84/16), Ni(COD)2 (0.015
mmol), pyridine (0.15 mmol), Mn (0.3 mmol), N,N-dimethylacetamide (DMA) (1
mL), 25 oC. b Isolated yields. c E/Z ratios were obtained by GC.
Table 2. Substrate scope for the coupling of α-halo carbonyl
compounds with β-styrenyl bromide derivatives.a,b,c
a
Method B: α-halocarbonyl compounds (0.15 mmol),
2 (0.3 mmol), Ni(COD)2
(0.015 mmol), pyridine (0.15 mmol), 2,2’-bipyridine (0.045 mmol), Mn (0.3 mmol),
DMA (1 mL), 25 oC. b Isolated yields. c The E/Z ratios were determined by GC. d α-
Chloro ester was used. e α-Bromo carbonyl compounds were used with addition
f
g
of 1 equiv of MgCl2. 1-Bromo-1-propene with E/Z ratio of 40/60. The E vinyl
bromide was used (E/Z > 99:1). h1-Bromo-1-nonene with E/Z ratio of 35/65.
Scheme 2. Method B for the coupling of 1b with 1-bromo-1-
propene.
A survey of a wide range of α-halo carbonyl compounds with a set
of β-styrenyl bromide derivatives was carried out using the standard
method A (Table 1, entry 1). Variations of the substituents on the
phenyl rings of the vinyl bromides generated the products 4–10 in
good to excellent yields, indicating that the electronic properties of
the conjugated arenes had a minor impact on the coupling efficiency.
However, use of the sterically more demanding (E)-(1-bromoprop-1-
en-2-yl)benzene gave 11 in diminished yield. Other alkyl 2-
chloropropanoate derivatives also proved to be effective, as evident
in the products 12–14. Vinyl bromides conjugated with naphthyl,
furyl, and styrenyl were all competent, providing 14–16 in good
yields. Moreover, the sterically more congested 2-bromohexanoate
a Standard conditions following method A as in Table 1, entry 1; unless otherwise
noted α-chlorocarbonyl substrates were used. b Isolated yields. c The ratio of E/Z >
99:1 for the vinyl bromide. d The ratio of E/Z = 84:16 for (2-bromovinyl)benzene. e
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resulted in the vinyl products 17–18 in satisfactory outcomes. The group tolerance. Whereas the E-vinyl halides generates exclusively E-
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present protocol was also applicable to α-bromoamides, wherein use products, the Z-vinyl groups in the vinyl hDaOlidI:e1s0.w10e3r9e/Cm6OoBd0e2ra26te9lCy
of MgCl2 as the additive was necessary, as manifested by the converted to the E-products.
products 19–21.
Extension of the optimized method A to alkyl-substituted vinyl
Acknowledges
bromides was not satisfying. The coupling of 1b with 1-bromo-1-
Financial support was provided by the Chinese NSF (Nos. 21172140,
21302127, 21372151 and 21572127), Shanghai Municipal Education
Commission for the Programs for Professor of Special Appointment
(Dongfang Scholarship) and Peak Discipline Construction (N.13-
A302-15-L02) and Shanghai Science and Technology Commission
(14DZ2261100). Dr. Hongmei Deng (Shanghai Univ.) is thanked for
use of the NMR facility.
propene only resulted in the product 36 in 10% yield. The yield was
boosted to 86% upon addition of 2,2'-bipyridine, wherein the E/Z
ratio of the starting vinyl group changed from 40/60 to 78/22 in the
product (Scheme 2). The coupling conditions displayed remarkable
compatibility with α-vinyl bromides, which has been sparsely
addressed in the concurrent reductive vinylation work.7b,11 Excellent
yields were obtained for 23–24. It should be noted that preparation
of α,α-dialkyl-substituted olefins remains a challenge using Heck
methods.18 For phenyl 2-bromobutanoate, MgCl2 was added, which
resulted in 25–26 in good yields. Likewise, the sterically more bulky
2-bromohexanoate was also competent for the coupling with (E)-2-
bromo-1-butene, 1-bromo-2-methyl-1-propene and (E)-(4-bromo-3-
buten-1-yl)benzene, which delivered 27–29 in good to excellent
yields. The compatibility of 2-bromoamides was examined for the
coupling with both α- and β-vinyl bromides. The vinylated amide
products 30–34 were obtained in good to excellent yields. Partial
conversions of the (Z)-vinyl groups of the halides to E-products were
also observed; 1-bromo-1-nonene with an E/Z ratio of 35/65 resulted
in that of 75/25 for 30 and 85/15 for 34, respectively.
Notes and references
1
Synthetic buiding blocks: (a) T. Ankner, C. C. Cosner and P.
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Yang, Z. Liu and K. L. Engle, J. Am. Chem. Soc., 2016, 138, 5805.
Bioactive: (a) H. Irschik, P. Washausen, F. Sasse, J. Fohrer, V. Huch,
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R. Müller and E. V. Prusov, Angew. Chem., Int. Ed., 2013, 52, 5402;
(b) N. Tsuji, M. Kobayashi, K. Nagashima, Y. Wakisaka and K. J.
Koizumi, Antibiot., 1976, 29, 1; (c) Y. Liu, S. C. Virgil, R. H. Grubbs
and B. M. Stoltz, Angew. Chem., Int. Ed., 2015, 54, 11800–11803;
(d) R. V. Edwankar, C. R. Edwankar and J. M. Cook, J. Org. Chem.,
2014, 79, 10030.
(a) M. Grigalunas, T. Ankner, P.–O. Norrby, O. Wiest and P.
Helquist, Org. Lett., 2014, 16, 3970; (b) Pd: J. Huang, E. Bunel and
M. M. Faul, Org. Lett., 2007, 9, 4343-4346; (c) A. Chieffi, K.
Kamikawa, A. Ahman, J. M. Fox and S. L. Buchwald, Org. Lett.,
2001, 3, 1897; (d) X. Liu and J. F. Hartwig, Org. Lett., 2003, 5, 1915.
Ni-catalyzed alkenylation of enolates, see: M. Grigalunas, T.
Ankner, P.–O. Norrby, O. Wiest and P, Helquist, J. Am. Chem. Soc.,
2015, 137, 7019.
In light of the previous mechanistic studies on the vinylation and
arylation of alkyl halides,7,19 we propose that this coupling event
proceeds through a radical-chain process wherein oxidative addition
of vinyl halides to Ni0 generates vinyl–NiII intermediates (Scheme 3).
The combination of a cage-escaped alkyl radical with the vinyl–NiII
species generates a NiIII complex that results in the product and Ln–
NiI–X upon reductive elimination. Halide abstraction or one-electron
reduction of alkyl halides by the NiI intermediate affords radicals and
a NiII species, which is reduced to Ni0 by Mn, allowing the catalytic
process to continue (Scheme 3).
3
4
5
For oxidative coupling of enolates with vinylmetallic reagents,
see: (a) E. Eduardas Skucas and D. W. C. MacMillan, J. Am. Chem.
Soc., 2012, 134, 9090−9093; (b) J. M. Stevens and D. W. C.
MacMillan, J. Am. Chem. Soc., 2013, 135, 11756; (c) H. Kim and
MacMillan, J. Am. Chem. Soc., 2008, 130, 398.
Scheme 3. Proposed catalytic cycle for the vinylation process.
6
7
(a) S. Lou and G. C. Fu, J. Am. Chem. Soc., 2010, 132, 5010; (b) X.
Dai, N. A. Strotman and G. C. Fu, J. Am. Chem. Soc., 2008, 130,
3302.
(a) D. A. Everson, B. A. Jones and D. J. Weix, J. Am. Chem. Soc.,
2012, 134, 6146; (b) K. A. Johnson, S. Soumik Biswas and D. J.
Weix, Chem. —Eur. J., 2016, 22, 7399.
8
9
For Pd-catalyzed in situ Negishi coupling, see: A. Krasovskiy, C.
Duplais and B. H. Lipshutz, Org. Lett., 2010, 12, 4742.
For the photoredox/Ni-catalyzed methods, see: (a) N. R. Patel, C.
B. Kelly, M. Jouffroy and G. A. Molander, Org. Lett., 2016, 18, 764;
(b) A. Noble, S. J. McCarver and D. W. MacMillan, J. Am. Chem.
Soc., 2015, 137, 624.
Conclusions
10 For reviews on reductive coupling of two electrophiles, see: (a) C.
E. I. Knappke, S. Grupe, D. Gärtner, M. Corpet, C. Gosmini and A.
J. Wangelin, Chem. ‒Eur. J., 2014, 20, 6828; (b) D. A. Everson and
D. J. Weix, J. Org. Chem., 2014, 79, 4793; (c) T. Moragas, A. Correa
and R. Martin, Chem. ‒Eur. J., 2014, 20, 8242; (d) D. J. Weix, Acc.
Res. Chem., 2015, 48, 1767; (e) J. Gu, X. Wang, W. C. Xue and G.
H. Gong, Org. Chem. Front,. 2015, 2, 1411.
11 Ni-catalyzed electrochemical: C. Cannes, S. Condon, M.
Durandetti, J. Périchon and J.-Y. Nédélec, J. Org. Chem., 2000, 65,
4575-4583.
In summary, we have demonstrated that vinylation of α-halo
carbonyl compounds with vinyl halides can be readily achieved under
mild, Ni-catalyzed reductive coupling conditions. For aryl-conjugated
vinyl halides, pyridine serves as the only labile ligand, whereas for
alkyl-decorated vinyl halides, the use of pyridine and bipyridine
necessitates the coupling event. In the latter case, α-vinyl functional
groups can be effectively incorporated. Both 2-haloesters and -
amides are suited for the coupling process, which afford the
vinylated products in good to high yields with excellent functional
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12 M. Durandetti, C. Gosmini and J. Perichon, Tetrahedron, 2007,
63, 1146.
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DOI: 10.1039/C6OB02269C
13 For Ni-catalyzed reductive arylation of unactivated alkyl halides,
see: (a) S. Wang, Q. Qian and H. Gong, Org. Lett., 2012, 14, 3352;
(b) D. A. Everson, R. Shrestha and D. J. Weix, J. Am. Chem. Soc.,
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K. M. Traister and B. T. O’Neill, J. Org. Chem., 2015, 80, 2907. (f)
Y. Peng*, J. Xiao, X.-B. Xu, S.-M. Duan, L. Ren, Y.-L. Shao, and Y.-
W. Wang, Org. Lett. 2016, 18, 5170; (g) Y. Peng, X.-B. Xu, J. Xiao,
Y.-W. Wang, Chem. Commun. 2014, 50, 472.
14 (a) A.H. Cherney, N. T. Kadunce and S. E. Reisman, J. Am. Chem.
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15 Y. Peng, L. Luo, C.-S. Yan, J.-J. Zhang and Y.-W. Wang, J. Org.
Chem., 2013, 78, 10960.
16 For pyridine-promoted arylation of tertiary alkyl halides, see: X.
Wang, S. Wang, W. Xue and H. Gong, J. Am. Chem. Soc., 2015, 137,
11562.
17 The reason for isomerization of vinyl halides under Ni- or Co-
catalyzed conditions have been discussed, but no conclusive
remarks have been reached, see Ref. 7b and (a) A. Moncomble,
Pascal Le Floch, A. Lledos and C. Gosmini, J. Org. Chem., 2012, 77,
5056. However, it is likely that the formation of a zwitterionic
C(carbene)-Ni intermediate accounts for this transformation, see:
(b) J. M. Huggins and R. G. Bergman J. Am. Chem. Soc. 1981, 103,
3002; (c) C. Clarke, C. A. Incerti-Pradillos and H. W. Lam, J. Am.
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18 For selected examples, see: (a) T. Nishikata, K. Nakamura, K.
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Bloome, R. L. McMahen and E. J. Alexanian, J. Am. Chem. Soc.,
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Meng and A. Lei, Angew. Chem., Int. Ed., 2012, 124, 3698; (d) R.
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19 S, Biswas and D. J. Weix, J. Am. Chem. Soc., 2013, 135, 16192.
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