Reviews and Accounts
ARKIVOC 2015 (i) 184-211
Recent advances in nickel-catalyzed C–H bond functionalized reactions Xiao-hua Cai* and Bing Xie Research Center for Karst Wetland Ecology, Guizhou Minzhu University, Guiyang 550025, P. R. China E-mail:
[email protected] DOI: http://dx.doi.org/10.3998/ark.5550190.p008.915 Abstract The direct C–H bond functionalization has been one of the most active research fields in organic chemistry not only due to the significance in basic studies of inert C–H bond chemistry but also due to the step economy feature in potential synthetic application. In the past decades, transition-metalcatalyzed direct and selective functionalization of C–H bonds has emerged as a straightforward and environmentally friendly synthetic tool, which is also a long-standing goal that continues to drive discovery in organic synthesis. The precious late transition metals have been proved to play key roles to facilitate highly efficient transformations through C-H functionalization. However, the relatively high price, low natural abundance and partly strong toxicity limited their application. Nickel, compared to precious transition metals, is showing great potential for C–H bond functionalizations because of its low cost, unique reactivity profiles and easy availability in the earth’s crust. This tutorial review summarizes the recent advances in nickel-mediated direct C–H bond functionalizations and C−C bond forming reactions. Keywords: C–H bond activation, functionalized reaction, C–C bond formation, nickel catalysts
Table of Contents 1. Introduction 2. Csp1-H Bond Functionalizations 3. Csp2-H Bond Functionalizations 3.1 Aldehydes C–H activation 3.2 Olefin and aromatic C–H activation 3.3 Heteroaromatic C–H activation 4. Csp3-H Bond Functionalizations 5. Conclusions
Page 184
©
ARKAT-USA, Inc
Reviews and Accounts
ARKIVOC 2015 (i) 184-211
1. Introduction Direct functionalization of unactivated carbon-hydrogen (C-H) bonds has been a focal point of experimental and theoretical research and plays an important role among these synthesis routes.1-7 A relatively inert C–H bond is activated, and the hydrogen atom acts essentially as a leaving group. This technology allows one to bypass the installation and subsequent removal of classical leaving groups and to reduce wastes as well as some precautions (such as protecting group manipulations) typical in the handling of promiscuous amine reagents. While developing a capable reactant or catalyst system that is chemo-, regio-, and stereoselective is highly challenging, various researchers have made significant contributions to this field.8-15 In the past decades, transition-metal-catalyzed direct and selective functionalization of C–H bonds has emerged as a straightforward and environmentally friendly synthetic tool, which is also a long-standing goal that continues to drive discovery in organic synthesis. Thus research on this subject has been attracting increasing interest amongst organic chemists, and various high efficiency and versatile protocols have been explored.16,17 In 2006, a simpler vision on the most common C-H bond functionalization mechanisms was provided by Sanford who described these as “inner-sphere” and “outersphere” mechanisms (Scheme 1).18-20 As defined by Sanford, the “inner-sphere” mechanism comprises two steps that involve the cleavage of the C-H bond leading to the formation of a transition metal alkyl or aryl derivative and the functionalization of this intermediate by an external reagent (or the metal center) to lead to final product. Concerning the “outer-sphere” mechanism, the first species formed is a high oxidation state metal complex containing an activated ligand. This reactive species can evolve by two different pathways, one is the direct insertion in the C-H bond and the second is a hydrogen atom abstraction/radical rebound furnishing the C-H bond functionalization product. R1 R2
H
M Cat. C-H bond cleavage
R1 R2
[M]
R1 R2
Functionalization
X
Inner-sphere mechanism [M] [M]
Oxidant Oxidation
[M] X +
R1 R2
R1 X
2+
H
H
Functionalization H
Outer-sphere mechanism
R1
[M]
.X
1 + R R2
R1 R2
H X
.
Scheme 1 In the past decades, most attention has been paid to the development of late transition metals, mainly due to some advantages in terms of the diversity and tunability of the catalysts and their robustness. The precious late transition metals, for example, palladium, ruthenium, rhenium and iridium catalysts have been shown to be effective for this catalytic system and have been proved to play key roles to facilitate highly efficient transformations through C-H activation. However, the relatively high price, low natural abundance and partly strong toxicity limited their application. Nickel is an abundant 1st row transition metal found in group 10 of the periodic table. Nickel Page 185
©
ARKAT-USA, Inc
Reviews and Accounts
ARKIVOC 2015 (i) 184-211
contains ten d-electrons in a neutral Ni(0) species and can exist in a variety of oxidation states Ni(0)–Ni(IV), the lower oxidation states Ni(0) and Ni(II) are the most common, while Ni(I) and the higher oxidation states Ni(III) and Ni(IV) are quite rare.21 Nickel compared to precious late transition metals, is easily available in the earth’s crust. In spite of showing great potential in the direct C–H bond functionalizations because of its low cost and unique reactivity profiles, the metal is comparatively underutilized.22 During the past several years, an increasing number of nickel catalyzed C–H functionalizations have appeared in the literature. This review will discuss recent discoveries in nickel-catalyzed C-H bond functionalized reactions and highlight the scope and the mechanism of these reactions.
2. Csp1-H Bond Functionalizations Carbon–carbon bond-formation reactions are among the most important processes in chemistry because they enable key steps in building more complex molecules from simple precursors. In the past several years, Nickel-catalyzed functionalization of C–H bonds for constructing new C-C bonds has emerged as a straightforward and environmentally friendly synthetic tool, which is also a long-standing goal that continues to drive discovery in organic synthesis. Samai et al23 developed an efficient NiCl2-catalyzed one pot coupling of aldehydes, amines afforded a diverse range of propargylamines in up to 95% yields (Scheme 2). The reaction had high atom efficiency, since water is the only byproduct. A possible mechanism (Scheme 3) was proposed for the probable sequence of events involving the activation of the C–H bond of alkyne 3 by NiCl2. The nickel–acetylide intermediate 4 generated by the reaction of acetylene and NiCl2 reacted with the iminium ion 5 (generated in situ from aldehyde 1 and amine 2) to give the corresponding propargylamine 6. R2 + R1 CHO + HN R3 (1 equiv) (1.5 equiv)
R4
H
(2 equiv)
NiCl2
R2
N
R3
toluene, 110 °C R1 Argon up to 95% yield
R4
1
R = Ph, p-MeC6H4, o-ClC6H4, p-MeOC6H4, p-ClC6H4, p-BrC6H4, m-NO2 2-Thiophen, m-Cl, Me2N, etc. HN
R2 3
R
= HN
Ph
HN
O HN
NH2
NHCH3
NH
Ph C6H5CHNH2, n-BuNH2, CH3NH2, NH3, N-Phenyl piperazine R4 = Ph, CH2(CH2)5, 4-MeOC6H4, (CH3)3Si
Scheme 2
Page 186
©
ARKAT-USA, Inc
Reviews and Accounts
ARKIVOC 2015 (i) 184-211
R2
NiCl2
N R1 6
NiCl2
R2
2
R2
R
H
H2O
R1 CHO + 1
H 3
N
N H 2
R1
5
NiCl2
HCl
4
Scheme 3
3. Csp2-H Bond Functionalization In 2006, Liang et al24 have reported an efficient intermolecular arene C-H activation protocol mediated by Ni(II) complexes under mild conditions. These studies directed to describe the reaction mechanism and reactivity with applicable hydrocarbons are currently underway. Later, Muto et al25 studied mechanistic of a C−H/ C−O biaryl coupling of 1,3-azoles and aryl pivalates using Ni(cod)2/dcype as catalyst. This study not only supports a catalytic cycle consisting of C−O oxidative addition, C−H nickelation, and reductive elimination but also provides insight into the dramatic ligand effect in C−H/C−O coupling. Investigations on kinetic studies and kinetic isotope effect disclose that the C−H nickelation is the turnover-limiting step in the catalytic cycle. PR2 N Ni R' PR2
AlMe3, C6H6 R = iPr,Cy; R' = H, 25 °C R = iPr,Cy; R' = Me, 80 °C
PR2 N Ni Ph PR2
Scheme 4 3.1. Aldehydes of C–H activation Nakao and coworkers26 developed regioselective hydrocarbamoylation of alkenes mediated by nickel/Lewis acid cooperative catalysis (Scheme 5). This catalytic system achieved the exceptionally high regioselectivity and would be highly useful as a protocol to access variously functionalized amides as well as a novel transformation of anti-Markovnikov selective functionalization of alkenes. The proposed catalytic cycle was shown in Scheme 6. Formamides coordinating to the Lewis acid catalyst through their carbonyl oxygen would undergo the oxidative addition of the C(sp2)-H bond to a nickel(0) species to give nickel hydride 8 via the formation of 2formamidenickel intermediate 7. Alkenes coordinate to the nickel center of 8 to form 9, which undergoes migratory insertion to give alkylnickel 10. Reductive elimination followed by ligand exchange reactions provides alkanamides and regenerate 7 to complete the catalytic cycle.
Page 187
©
ARKAT-USA, Inc
Reviews and Accounts
ARKIVOC 2015 (i) 184-211 Ni(COD)2 (5 mol%) IAd (5 mol%)
O R1
N H + R3 R2 (1.0 mol) (1.5 mol)
O R1
AlEt3 (20 mol%) toluene, 100 °C, 2-26h
N
R3
N R2
..
N
IAd
R1, R2 = (Et, Et), R3 = CH3(CH2)10, 69%;;
R1, R2 = (Me, Bn), R3 = CH3(CH2)10, 68%
R1, R2 = (Bn, Bn), R3 = CH3(CH2)10, 75%;
R1, R2 = (Me, Ph), R3 = CH3(CH2)10, 13%
1
2
3
R , R = (Me, Me), R = t-BuSi(Me)2O(CH2)3, 77%; R1, R2 = (Bn, Bn), R3 = t-Bu 13% R1, R2 = (Me, Me), R3 = t-BuCOO(CH2)3, 59%; 1
2
R1, R2 = (Bn, Bn), R3 = t-Bu 59%
3
R , R = (Bn, Bn), R = (Me)3Si, 59%;
R1, R2 = (Bn, Bn), R3 = Ph, 59%
R1, R2 = -(CH2)5-, R3 = CH3(CH2)10, 65%;
R1, R2 = -(CH2)O(CH2)2-, R3 = CH3(CH2)10, 53%
O Bn Ph
N
O Bn 10
81%; >95ee
O Me
N
Ph
10
78%; >95ee
N Me
90%
Scheme 5 O R1
R1 R2
N
O AlEt3
R3
N R2 O
Ni L 7
H AlEt3 H
N 10
Ni L
O AlEt3 H N Ni 8 L
L = IAd R3 O AlEt3 H N Ni 9 L
R3
R3
Scheme 6 In 2011, Hiyama and co-workers27 made a significant achievement for the development of cycloaddition of formamides and alkynes through activation of both C(sp2)-H and C(sp3)-H bonds (Scheme 7). Hiyama et al.28 originally discovered a nickel catalyst system that facilitates hydrocarbamoylation of unsaturated bonds such as alkynes (Scheme 8 cod=cyclooctadiene). This study reveal that Lewis acid plays a critical role in activating the formamides towards C(sp2)-H activation.29,30 With this Lewis-acid assistance, [Ni] oxidatively adds the C(sp2)-H bond of the formamide. Alkyne insertion followed by C-C bond-forming reductive elimination provides highly substituted acrylamides.
Page 188
©
ARKAT-USA, Inc
Reviews and Accounts
ARKIVOC 2015 (i) 184-211 O O Ar
{Ni(cod)2] (1-10 mol%) P(tBu)3 (4-40 mol%) AlMe3 (20 mol%)
R
N
H H
Ar
+
Ar
R
N Ar
R + R1
toluene, 80 °C
R
Ar
H
R
H
R
+
R2
N O
Ar
Scheme 7
R
[Ni(cod)2] (10 mol%)
R1
O H
M R
P(tBu)3 (40 mol%)
+
O
Lewis acid (20 mol%) R 2
R2
M R
toluene, 80 °C
R
R1
Scheme 8 O Ar Ar
O N
Ar
Ar
OLA
R Ar
H H
Ar
R
N
N
H Ni0Ln
Ar O LA N
Ar
11
NiLn
OLA
R 15 R O LA
R
R
N
Ar Ar R
H
R
H
sp2 C-H activation
Ar 12
N Ar
H NiLn R
Ni 14
LA O Ar
N Ar
R R
Ni Ln
R
H 13
H sp2 C-H activation dehydrogenative coupling
Scheme 9 Building upon this work, Hiyama and co-workers31 found N,N-bis(1-arylalkyl) formamides not only undergo the Lewis acid-assisted oxidative addition of the formamide C(sp2)-H bond, the resultant nickel intermediate inserts an alkyne and undergoes a second C-H activation (Scheme 9). That is, intermediate 13 converts to intermediate 14 through cyclometalation of the alkyl C(sp3)-H bond and extrusion of a reduced alkyne (i.e., an alkene). Although this type of cyclometalation is prevalent for platinum metals, cyclometalation on nickel is much less prevalent.32-34 In addition,
Page 189
©
ARKAT-USA, Inc
Reviews and Accounts
ARKIVOC 2015 (i) 184-211
examples of Ni-based cyclometalation has been mainly limited to the activation of C(sp2)-H bonds.35,36 In contrast this nickelacycle 14 inserts a second alkyne and reductively eliminates the dihydropyridone product to complete the catalytic cycle. The work of Hiyama and co-workers is certainly an outstanding contribution in the field of cross-dehydrogenative coupling. Key to their success was an optimal steric environment around the metal center to promote cyclometalation/ dehydrogenative coupling. These findings mark the entry of a cheaper, first-row transition metal catalyst nickel in mediating C-C bond formation through the challenging C(sp3)-H activation. 3.2. Olefin and aromatic C–H activation In 2008, Tekavec and Louie37 developed the cycloisomerization of enynes to afford 1,3-dienes using the combination of Ni(0) and an N-heterocyclic carbene acted as a precatalyst (Scheme 10). During the course of the reaction, a nickel hydride was formed from oxidative addition of the ortho C–H on the carbene ligand. In mechanism A (Scheme 11), the enyne undergoes oxidative coupling with the Ni(0) catalyst to generate a metallacyclopentene. This metallacyclopentene undergoes βhydride elimination to provide a vinyl nickel hydride. Then the vinyl nickel hydride reductively eliminates to yield the observed 1,3-diene. Alternatively, in mechanism B (Scheme 11), the alkyne component of the enyne undergoes hydrometalation with a Ni–H complex to produces a vinyl nickel species. The pendant olefin then inserts into the vinyl nickel bond thereby forming an alkyl nickel species. β-Hydride elimination and reductive elimination affords the observed 1,3-diene. The combination of Ni(cod)2 and IDTB catalyzes the cycloisomerization of enynes to synthetically valuable cyclic 1,3-dienes. Deuterium labeling studies suggest that the active catalyst species is a Ni–H species generated via a rare Ni(0) C–H activation. E
Ni(COD)2 (5 mol%) IDTB (10 mol%)
E E E
R
E
E
toluene, 60 °C
E = COOEt EtOOC EtOOC
R = Me, 90%; R = Et, 92%; R = n-Pr, 97%; R = i-Pr, 99%;
t-Bu
E E
t-Bu
.. R
t-Bu
IDTB
t-Bu
82%
Scheme 10 Ni0
Ni0 H
H
Ni
Ni H H
H
H
Ni
H H Ni Mechanism B
Mechanism A
Scheme 11
Page 190
©
ARKAT-USA, Inc
Reviews and Accounts
ARKIVOC 2015 (i) 184-211
Yoshida et al38 developed a nickel-catalyzed cycloaddition of α,β-unsaturated oximes with alkynes to afford 2,3,4,6-tetrasubstituted pyridine derivatives (Scheme 12 and 13). The reaction involved oxidative addition of the NO bond of α,β-unsaturated oximes to Ni(0) and subsequent alkyne insertion to an N-Ni bond, followed by intramolecular cyclization. It was also found that α,βunsaturated oximes participate in the nickelcatalyzed reaction with alkynes to furnish pyridine derivatives. Based on the results, a proposed reaction pathway was show in Scheme 14. The oxidative addition of an oxime NO bond to an Ni(0) complex initiated the reaction, followed by insertion of an alkyne into an N-Ni bond to generate intermediate 17. The subsequent intramolecular insertion of the olefin produces intermediate 18. The methoxy ligand on the nickel would then be replaced with i-PrOH to provide 19. This ligand-exchange reaction of intermediate 18 with i-PrOH to lead to intermediate 19 is the rate-determining step in the catalytic process. βHydride elimination will give 20, and a second β-hydride elimination, with aromatization of the sixmembered heterocycle, would provide pyridine 21. N OMe R1
R4
Ni(COD)2 (10 mol%) +
R3
IPr (10 mol%)
R4
R2
R3
N
i-PrOH toluene, 130 °C, 3 h
1
..N
2
R
R
IPr
R1 = R2 = Ph, R3 = R4 = Pr, 75%;
R1 = Ph, R2 = Me, R3 = R4 = Pr, 71%;
R1 = Me, R2 = Ph, R3 = R4 = Pr, 29%;
R1, = t-Bu, R2 = Me, R3 = R4 = Pr, 70%;
R1 = 4-CF3-C6H4, R2 = Ph, R3 = R4 = Pr, 85%; R1, = 4-MeO-C6H4, R2 = Ph, R3 = R4 = Pr, 78%; R1 = Ph, R2 = 4-F-C6H4, R3 = R4 = Pr, 85%;
R1, = Ph, R2 = 4-MeO-C6H4, R3 = R4 = Pr, 83%;
R1 = Ph, R2 = Ph, R3 = Pr, R4 = Me 85% ( Ratio of regioisomers = 2:1)
Scheme 12 N OMe R1 1
3
Ph +
R3
R4
IPr (10 mol%)
4
3
N
i-PrOH(5 equiv) toluene, 130 °C, 3 h 1
R = Ph, R = R = Pr, 75%; 1
R4
Ni(COD)2 (10 mol%)
R1 3
R3 Ph
4
R = 4-F-C6H4, R = R = Pr, 67%;
4
R = 4-MeO-C6H4, R = R = Pr, 23%;
R1 = Ph, R3 = Pr, R4 = Me 59% ( Ratio of regioisomers = 5:1)
Scheme 13 In 2011, Ogata and coworkers39 reported a diastereoselective three-component coupling reaction between aryl aldehydes, norbornenes (norobornadiene), and silanes leading to silylated indanol derivatives using a [Ni(cod)2]/N-heterocyclic carbene catalyst system (Scheme 15). This was the first example of a nickel-catalyzed reductive three-component reaction involving aromatic C-H bond activation of aryl aldehydes. A possible pathway for the three-component reaction is shown in Scheme 16.
Page 191
©
ARKAT-USA, Inc
Reviews and Accounts
ARKIVOC 2015 (i) 184-211 H2
Pr
N OMe
Pr
N
NiH2
Ph
Ph
NI(0)/IPr
Ph 21 Ph Ph
N H O
Ni H Ph
Ph
OMe N Ni
Pr Pr
Pr
20
N
Ph N O
Ni
Pr
Ph
Pr MeOH
19
Ph
17
Pr
N i-PrOHPh
Ni OMe
Ph
Pr
Pr
Pr
Pr
H
16
Ph
Ph Ni
18
OMe
Scheme 14
R
OSi(iPr)3
[Ni(COD)2] (10 mol%)
O
N
L (10 mol%)
H+
+ (iPr)3SiH
THF, r.t., 15 h
.. N
R
R = Ph ,
82%; R = 4-Me ,
84%; R = 4-MeO,
R = 4-F ,
94%; R = 4-CO2Me , 73%; R = 3-Me,
R = 2-F ,
33%; R = 3,5-2Me , 77%
99%; R = 4-Cl ,
51%;
87%; R = 3-F ,
55%;
Scheme 15 O H
H
H
(Pr)3SiH
O Ni L
Ni0L
(Pri)3SiO H Ni L
OSi(iPr)3 Ar
Ni0L Si(iPr)3 O H
Si(iPr)3 O H
OSi(iPr)3
Ni
Ni0L L
H2
H Ni H
L
Scheme 16 In 2013, Yoshinori and Naoto40 described the alkylation of the ortho C–H bonds in benzamides and acrylamides containing an 8-aminoquinoline moiety as a bidentate directing group with unactivated alkyl halides using nickel complexes as catalysts in good yields (Scheme 17). The reaction showed high functional group compatibility. In reactions of meta-substituted aromatic amides, the reaction smoothly proceeds in a highly selective manner at the less hindered C–H bond. Page 192
©
ARKAT-USA, Inc
Reviews and Accounts
ARKIVOC 2015 (i) 184-211 O
Ni(OTf)2 (10 mol%)
O +
N H
N
H
PPh3 (20 mol%) Na2CO3 (2 equiv) (2 equiv) toluene, 140 °C, 24 h
N H
R Br
R
N
up to 96% yield
R = Bu, Oct, CH2Ph, (CH2)4CN, (CH2)3OMe, (CH2)3COOMe (CH2)2Ph, CH2CH(Me)2, CH2CH2CH(Me)2, etc
Scheme 17 Nakao et al41 found a Ni catalyst for the activation of C-H over C-F bonds of polyfluoroarenes and demonstrated their direct alkenyl- and alkylation to allow efficient synthesis of a variety of polyfluoroarenes having alkenyl and alkyl groups in regio- and stereoselective manners (Scheme 18). Experimental and theoretical mechanistic studies determine the origin of the dramatic ligand effect on the Ni catalysis for C-H activation of polyfluoroarenes. F F
{Ni(cod)2] (3-10 mol%)
F +
F
H F (1.0 mmol) R1, R2 = Pr, Pr 1
PCyp3 (10 mol% R R (1.5-3.0 mmol) toluene, 80 °C, 3-15 h 1
99%
2
R , R = Ph, Ph 68%
2
R1, R2 = CH2SiMe3, CH2SiMe3 C6F5 Me C6F5
C6F5 SiMe3 47%
Me
F
F H 1 F R
R2
75%
89%
tBu
Me
F F
SiMe3
63%
Scheme 18 In 2010, Johnson and coworkers42 reported the nickel-catalyzed reaction of fluorinated arenes and pyridines with vinyl stannanes does not provide the expected vinyl compounds via C-F activation but rather provides new Sn-C bonds via C-H functionalization with the loss of ethylene (Scheme 19). Unlike the B-C bonds used in the Miyaura-Suzuki coupling reaction, which are readily obtained via direct borylation of C-H bonds, the reaction provides a novel unanticipated methodology for the direct conversion of C-H bonds to carbon-heteroatom bonds. Fn H
+
SnBu3
Fn
Ni(COD)2 Me N
N
SnBu3 + C2H4 iPr up to 98% yield
i
or P Pr3,
Scheme 19
Page 193
©
ARKAT-USA, Inc
Reviews and Accounts
ARKIVOC 2015 (i) 184-211
Later, Mao and coworkers43 reported Ni(OAc)2·4H2O could catalyze the direct C–H arylation of unactivated arenes with aryl halides in presence of 1,10-phenanthroline without using additives (Scheme 20). This protocol provides more useful C–H arylation via activation of aromatic C-H Bond. Shiota et al44 achieved the first example of the Ni-catalyzed transformation of ortho C-H bonds utilizing chelation assistance and realized the regioselective oxidative cycloaddition of aromatic amides to alkynes (Scheme 21 and 22).
(20 mol%) N N Ni(OAc)2 4H2O (10 mol%)
.
X
Ar H +
R
Ar R
KOtBu (4 equiv) 90 °C, in Ar, 24 h
32-90% yield
Ar = C6H5, nathphyl,1,4-2MeC6H4, pyridinyl R = H, 4-MeO, 4-Me, 4-F, 4-Br, 4-Cl, 3-Me, 3-MeO
Scheme 20 O N H
R
N
H (0.5 mmol)
{Ni(cod)2] (10 mol%) PPh3 (40 mol%
Pr + Pr (1.5 mmol)
toluene, 160 °C, 6 h
O NR'
R
Pr Pr
R = H, 86%;
R = 4-Me, 84%;
R = 4-OMe, 73% ;
R = 4-CF3, 91%;
R = 4-Ac, 85%;
R = 2-Ph, 52%; O
R = 3,4-2MeO 84% O
R = 4-CN, 73% ; R = 4-Ph, 87% O R=, 87%; O O O F3CO H3CO NR' NR'
NR'
NR'
Pr
90% Pr
Pr
90% Pr
R = 4-NMe2, 69%
Pr 87% Pr
Pr 84% Pr
Scheme 21 O N H
N
H (0.5 mmol)
R + R (1.5 mmol)
Bu
Ar Ar
Ar = 4-CF3-C6H4 98% Ar = Ph 92% Ar = 4-MeO-C6H4 67%
NR' Ph Me 52% (13:1) O
O NR'
Ph Et 75% (16:1)
R R
O NR'
NR'
O NR'
NR' Bu
O
toluene, 160 °C, 6 h
O
O
90%
{Ni(cod)2] (10 mol%) PPh3 (40 mol%
Ar Bu
Ar = 4-CF3-C6H4 90% (21:1) Ar = Ph 75% (27:1) Ar = 4-MeO-C6H4 20%(>50:1)
NR' Ph tBu 84% (28:1)
Scheme 22 Page 194
©
ARKAT-USA, Inc
Reviews and Accounts
ARKIVOC 2015 (i) 184-211
In 2013, Lei and coworkers45 developed the aromatic C–H alkylation with tertiary or secondary alkyl–Br bonds for the construction of indolones using nickel catalysis (Scheme 23). Various functional groups were well tolerated in the reaction. Moreover, the challenging secondary alkyl bromides were well introduced in this transformation. Radical trapping and photocatalysis conditions exhibited that it is most likely to be a radical process for this aromatic C–H alkylation. R3 R1 R2 N Br O
R
R3 N
Ni(PPh3)4 (5mol%) dppp (6 mol%l)
R
K3PO4 toluene, 100 oC, 24 h R = H, N(Me)2, MeO, CH3CO, CN, Me, CF3,NO2, Cl, F, Br, I, etc. R1, R2, = H, Me; R3 = Me, Bn dppp =
O R1 R2 44-96%
Ph
Ph P
Ph P Ph
Scheme 23 3.3. Heteroaromatic C–H activation A pyridine core plays a key role in a number of natural products, pharmaceuticals and functional materials. Because a wide variety of pyridine derivatives are available, a strategy to install substituents directly into a preformed pyridine core has advantages in terms of step economy as well as versatility. In 2010, Nakao et al46 achieved the direct C-4-selective alkylation of pyridines using nickel/Lewis acid cooperative catalysis with an N-heterocyclic carbene ligand (Scheme 24). In this reaction, a variety of substituents on both alkenes and pyridine are tolerated to give linear 4alkylpyridines in modest to good yields. The addition across styrene, on the other hand, gives branched 4-alkylpyridines. These results imply a catalytic cycle initiated by oxidative addition of the C(4)-H bond of pyridine coordinating to MAD, which is kinetically favored over that of the C(2)-H and C(3)-H bonds, through η2-arene nickel species 24 (Scheme 25). Coordination and migratory insertion of alkenes into the Ni-H bond of nickel(II) intermediate 25 takes place to give alkylnickel 26 through 25, and subsequent reductive elimination gives C-4-alkylated pyridines 28 and regenerates 24. N
R1
+
R2 (1.5 mmol)
{Ni(cod)2] (5 mol%) IPr (5 mol%)
N
MAD (20 mol%) toluene, 130 °C, 3-23 h R1 = H, Me, 2,6-2Me, 3-CO2Me
(1.0 mmol)
R2 = C11H23, CH2Ph, (CH2)3OSiMe2t-Bu, (CH2)3OPiv,
R1
+
N
R1
2
R 22 23 R2 up to 95% yield (3 + 3') 22 : 23 up to > 95 : 5
(CH2)2CH=CH2, cyclohexen-4yl, SIMe3, Ph MAD = (2,6-t-Bu2-4-Me-C6H2O)2AlMe N
+ Pr
(1.0 mmol)
(3 mmol)
Pr
{Ni(cod)2] (5 mol%) IMes (5 mol%) AlMe3 (20 mol%) toluene, 110 °C, 5 h
Pr
N Pr Pr 53%
+ N
Pr 15%
Scheme 24 Page 195
©
ARKAT-USA, Inc
Reviews and Accounts
ARKIVOC 2015 (i) 184-211 Al N
Al N 28
R 24 Ni0 H
N
L = IPr Al = MAD
L Proceeds exclusively at the C-4postion
Al N
Al N
25
27 NiII L
R
operates also at the C-2 and C-3 postion
H
NiII L
Al
R
N NiII
26 L
H R
Scheme 25 The imidazole ring is an important structural motif encountered in numerous biologically active compounds ranging from natural products to pharmaceuticals.47 In 2009, Nakao and coworkers48 found Nickel/Lewis acid binary catalysis was effective to direct regioselective alkenylation of imidazoles through C–H bond activation and stereoselective insertion of alkynes (Scheme 26 and 27). Use of P(t-Bu)3 as a ligand allowed exclusive regioselective C(2)-alkenylation, while PCyp3 was found effective for C(5)-alkenylation of C(2)-substituted imidazoles. Results of the reaction revealed a broad scope of imidazoles and internal alkynes to give trisubstituted ethenes with highly regio- and stereoselectivities in modest to good yields. R2 N
Ni(COD)2 (3 mol%) N R1 +
H (3.0 mol)
R3
R4 (1.0 mol)
R2
P(t-Bu)3 (12 mol%) AlMe3 (6 mol%) toluene, 100 °C, 2-26h
N
N R1
R3
R1 = PhCH2, R2 = H, R3 = R4 = Pr, 63%, E/Z = 93:7
R4
R1 = Ph, R2 = H, R3 = R4 = Pr, 42%, E/Z = 92:8 R1 = Me, R2 = Ph, R3 = R4 = Pr, 63%, E/Z = >99:1 R1 = Me, R2 = H, R3 = R4 = Ph 75%, E/Z = <1:99 R1 = Me, R2 = H, R3 = R4 = 4-MeOC6H4 53%, E/Z = <1:99 R1 = Me, R2 = H, R3 = Ph, R4 = SiMe3, 69%, E/Z = 20:80 R1 = Me, R2 = H, R3 = Hex, R4 = SiMe3, 60%, E/Z = >99:1
Scheme 26
Page 196
©
ARKAT-USA, Inc
Reviews and Accounts
ARKIVOC 2015 (i) 184-211 H N Me +
N
R3
1
R (3.0 mol)
R3
Ni(COD)2 (3 mol%)
1
P(t-Bu)3 (12 mol%)
R4 (1.0 mol) 3
N
AlMe3 (6 mol%) toluene, 100 °C, 2-26h
R4
N Me R1
4
R = Ph, R = R = Pr, 8%, E/Z = >95:5 R1 = Me2Sit-Bu, R3 = R4 = Pr, 42%, E/Z = 96:4 R1 = Me, R3 = Hex, R4 = SiMe3, 63%, E/Z = >95:5 R1 = Me, R3 = Me R4 = i-Pr, 75%, E/Z = >95:5 R1 = Me, R3 = Me, R4 = t-Bu 71%, E/Z = >95:5
Scheme 27 Nakao, Hiyama and coworkers49 demonstrated the nickel-catalyzed hydroheteroarylation of vinylarenes to exclusively give a variety of 1,1-diarylethanes that contain a heteroaryl motif (Scheme 28 and 29). The use of relatively electron-poor heteroarenes in this reaction is complementary to the well documented Friedel–Crafts-type hydroarylation of vinylarenes with electron-rich arenes to give a wide variety of 1,1-diarylethanes. A plausible catalytic cycle that is initiated by reversible oxidative addition of an Ar-H bond to the nickel(0)/IMes catalyst to give nickel hydride 33 through η2-arenenickel 32 (Scheme 30). The coordination of vinylarenes 34 and subsequent hydronickelation are both reversible and give 1-arylethylnickel 36, that reductively eliminates 1,1-diarylethanes irreversibly to regenerate 32. The final step could be the ratedetermining step, as has been discussed previously for the nickel-catalyzed hydrocyanation50 and hydroalkynylation51 of vinylarenes. The primary reaction pathway could compete with the coordination and migratory insertion of alkenes to give 1,2-diarylethanes via 35 and 37. CO2Me N Me (1.0 mmol)
CO2Me
[Ni(COD)2] (5 mol%) +
Ar
N
IMes (5 mol%)
(1.5 mmol)
N Ar Me
i-PrOH(5equiv) hexane, 130 °C, 2-32 h
.. N
IMes
up to 100% yield
Ar = Ph, substitued Ph, 2-naphthyl, C11H23, etc.
Scheme 28
heteroarene + COMe N Ph 89% Me N O Ph 41%
[Ni(COD)2] (5 mol%) IMes (5 mol%) Ph
HetAr
hexane, 130 °C, 2-23 h CN
N
N Ph 85% Me
Ph N
N Ph 86% Me
O 97%
Ph
N S 81%
Ph
O 77%
Ph
Scheme 29
Page 197
©
ARKAT-USA, Inc
Reviews and Accounts
ARKIVOC 2015 (i) 184-211 Y
Ni0L H X 32
Y Ar
X 30
Y
Y Y L
Y Ni X 36 Ar
Ni
37 X
H
R
X
29 29X
31 L Ni X L
Y 35
Ni
X or
H
33
H
R Y
L Ni
34
L
Y
R
X Ar
H
Scheme 30 Qu et al52 developed a useful process for nickel-catalyzed direct sp2 C–H bond arylation of purines at room temperature in good yields (Scheme 31). This reaction was the first example that uses Grignard reagent as the coupling partner to perform direct sp2 C–H bond arylation of Naromatic heterocycles without a directing group. This approach provided a new access to a variety of C8-arylpurines which are potentially of great importance in medicinal chemistry. A possible mechanism that accounts for C–H bonds arylation of purine with Grignard reagents is presented in Scheme 32. Combination of 38 and Ni(dppp)Cl2 provides the metalated intermediate 39. Subsequently, an (aryl)-nickel(II) intermediate 40 is generated by transmetalation between aryl Grignard reagent and the metalated intermediate 39. Followed by reductive elimination to produce the desired product 41, the Ni(0) species 42 is generated, which is reoxidized to Ni(II) species by DCE to complete the catalytic cycle. R1 N
N
+ ArMgBr
N2, THF, r.t., 5 h
N
N
DCE (3 equiv)
N N (8 equiv) R3 (1 equiv) R1 = OMe, Ph, Bn, Cl, Benzylthio
2
R
R1
{Ni(dppp)Cl2] (30 mol%) R2
Ar N R3 41-91% N
R2 = H, Cl R3 = Bn, Phenethyl, Me, Et, n-Pr, cyclopentyl, n-Bu Ar = 3-MeC6H4, 4-MeC6H4, 4-MeOC6H4, 4-EtC6H4,3,5-2MeC6H4, 4-PhC6H4, 2-MeC6H4
Scheme 31
Page 198
©
ARKAT-USA, Inc
Reviews and Accounts
ARKIVOC 2015 (i) 184-211 R
R
Cl
N
NiIICl2
Ni0
N
N
N
Cl
H N 38 R
N
42
HCl
Ar N 41 R
N
R R N
N
N 40
N R
NiII
N
N
N 39
N R
Ar
NiIICl
ArMgBr 2 MgBrCl
Scheme 32 Itami and coworkers53 described the C–H bond arylation of azoles with phenol derivatives including esters, carbamates, carbonates, sulfamates, triflates, tosylates, and mesylates using a Ni(cod)2/dcype catalytic system (Scheme 33). The reaction provided the synthesis of a series of privileged 2-arylazoles including biologically active alkaloids, and the functionalizing estrone and quinine were obtained in 52% and 42% yield. Ni(cod)2 (10 mol%) N
dcype (20 mol%)
N
Cs2CO3 (1.5 equiv )
Z
H + RO Ar Z Z = O, S (0,4 mmol)
Ar
R = COt-Bu, Tf 1,4-dioxane, 120 °C, 12 h
42-99%
(1.5equiv)
Ar = Ph, substitued Ph, naphthyl, pyridyl, quinolinyl etc. Me
O
H Ph
N
H
O N
N
O
OH 42%
52% N
Scheme 33 In 2012, Iaroshenko et al54 reported the arylation of imidazo[4,5-b]pyridines known as 1deazapurines catalyzed by transition-metal (Scheme 34). 1-Deazapurines were generated from 5aminoimidazoles by the reaction of methyl N-(cyanomethyl)formimidate with primary amines. Later, Qu and coworkers55 developed a method for nickel-catalyzed direct sp2 C–H bond alkylation of N-aromatic heterocycles using a Grignard reagent as the coupling partner (Scheme 35 and Scheme 36). In this process, a variety of alkylated N-aromatic heterocycles with potentially of great importance in medicinal chemistry were obtained under mild condition.
Page 199
©
ARKAT-USA, Inc
Reviews and Accounts
ARKIVOC 2015 (i) 184-211 1) R1
MeO
NH2
CF3
CH2Cl2, reflux N
CN
O 2) F3C
O
N
2
reflux
CF3 ArX, K2CO3
N
R
N
1
R
R2
N Ar
NiCl2(PPh3)2 DMF, 110 °C
R1 = tBu, R2 = Me, 69% R1 = Cyclohexyl, R2 = Ph, 70% R1 = PhCH2CH2, R2 = 2-Thienyl, 75%
N
N
1
R
R2
Ar = 3-CF3C6H4 X = Br, 88% Ar = 2-FC6H4 X = Br, 92% Ar = Ph X = Br, 94%
R1 = p-methoxybenzyl, R2 = 2-Furyl, 75% Ar = 4-CH3C6H4 X = I, 93%
Scheme 34 N + Alk
MgBr
Ni(dppp)Cl2 (20 mol%) DCE (3 equiv)
N N2, THF, r.t., 24 h R R = Bn, Phenethyl, Me, nPentyl Alk = Bn, CH3(CH2)4
N Alk N R 47%-82% yield
Ph dppp = Ph P
Ph P Ph
Scheme 35 R1 N
N
+ Alk
MgBr
Ni(dppp)Cl2 (20 mol%) DCE (3 equiv)
N R R1 = MeO, Cl, 4-EtC6H4 R2 = Bn, cyclo-Pentyl, Me, Et N
N2, THF, r.t., 24 h
N Alk N R 53%-94% yield
Alk = Bn, CH3(CH2)4, CH3CH2,
Scheme 36 In early 2012, Itami et al56 disclosed a C-H arylation of azoles with C-O electrophiles, catalyzed by the combination [Ni(cod)2]/dcype (cod=1,5-cyclooctadiene, dcype=1,2-bis(dicyclohexylphosphino)ethane) (Scheme 37). This catalyst system was highly efficient for the coupling of esters, carbamates, sulfamates, triflates, tosylates, and mesylates with several compounds with an acidic C-H group, such as benzoxazoles, oxazoles, benzothiazoles, and thiazoles. Not surprisingly, the use of simpler alkyl ethers (C-OMe) as electrophiles did not give any conversion at all, thus illustrating the greater inertness associated with the C-OMe bond.57-60 Interestingly, the coupling of benzoxazole with phenyl thiophene-2-carboxylate did not give the expected C-H/C-O coupling process, but the formation of the corresponding bis(heteroaryl) backbone. In the reaction, a wide variety of heteroaromatic phenyl esters, including furans, thiophenes, pyridines, thiazoles, and quinolones were smoothly coupled with benzoxazoles,
Page 200
©
ARKAT-USA, Inc
Reviews and Accounts
ARKIVOC 2015 (i) 184-211
oxazoles, and thiazoles, to access bis(heteroaryl) motifs in a straightforward fashion. The authors reasonably speculated that the decarbonylative C-H arylation protocol involved a Ni0/NiII catalytic cycle (Scheme 38).61 This novel C–H arylation reaction was successfully applied to a convergent formal synthesis of natural product muscoride A with exceptional antibacterial activity (Scheme 39). R ≠ HetAr O
N
N
Cs2CO3 (2.0 equiv ) 1,4-dioxane, 120 oC, 12 h
Ar Z
Ar (1.5equiv)
H + R O Ni(cod)2 (10 mol%) dcype (20 mol%)
Z Z = O, S (1 equiv)
42-99% R = HetAr K3PO4 (2.0 equiv )
Slectivity switch depending on the chesen electrophil
N HetAr
o
1,4-dioxane, 150 C, 24 h
Z 52-96%
Scheme 37 O [Ni0(CO)n]
CO extrusion [Ni0(CO)n+1]
n+1
Oxidative addition
H
Z
Ar
CO migration
N Z
N
O
PhO NiII (CO)n
Ar
Ar (CO) NiII
Reductive elimination
PhO
PhO
NiII (CO) n+1
N
Ar
Ar Z
Scheme 38 Me
Ot-Bu
O
OMe O
O
H
O
OtBu +
N
O
Me
K3PO4 (2.0 equiv )
O
O
OMe
H
N
N
N
O
1,4-dioxane, 150 °C, 24 h
N
PhO
Ni(cod)2 (10 mol%) dcype (20 mol%)
Me
O 39%
Me H O
Me
Me
H N Me Me O O N N Me
O
Me H
Me
N H
muscoride A
Me
Scheme 39 The novel decarbonylative C-H arylation reported by Itami et al. will open up new opportunities and stimulate the development of new concepts and ideas within the field of Ni-catalyzed reactions, which is probably one of the most vibrant and promising branches of current research in organic and organometallic chemistry.62 Transition metal catalyzed alkenylation is one of the most reliable methods for making alkenylsubstituted arenes as exemplified by the Mizoroki–Heck reaction.63 In 2013, Yamaguchi and
Page 201
©
ARKAT-USA, Inc
Reviews and Accounts
ARKIVOC 2015 (i) 184-211
coworkers64 developed Ni/dcype catalyzed C-H/C-O alkenylation and decarbonylative C-H alkenylation two novel C-H alkenylations of azoles (Scheme 40). These newly developed azole alkenylation reactions were successfully applied to the convergent formal synthesis of siphonazole B.65 N
+
H
{Ni(cod)2] (10 mol%) dcype (20 mol%)
RO
Ph
Z
N
K3PO4, 1,4--dioxane
Z R 130 °C, 12-36 h R = tBuCO up to 51% yield
Z = O, S
R = Me2NCO up to 70% yield N
O
+
H O
{Ni(cod)2] (10 mol%) dcype (20 mol%)
N
K3PO4, 1,4--dioxane 130 °C, 12-36 h
Z
R
PhO
1.5 equiv
R
47-87%
R = Ph. 4-MeOC6H4, 3,4-2MeOC6H4, 2-MeC6H4, 2-thienyl, 3-oxazyl, Me, Et, etc.
Scheme 40 Recently, Zhang, Ge and coworkers66 developed an efficient Ni-catalyzed ligand-free direct decarboxylative acylation of azole derivatives by means of sp2 C-H bond functionalization with good to excellent yields (Scheme 41). This transformation is the first example of decarboxylative cross-coupling reactions using Ni catalysis by a C-H bond functionalization pathway, and provides an useful complementary protocol to access important heteroaryl ketone derivatives in the field of synthesis and medicine. H +
R'
X
Ni(ClO4)2 6H2O (7.5 mol%) COOH
(0.6 mmol)
(0.2 mmol)
O
N
R N
O
O
Ph
MeO2C
R = H, R = 7-Cl,
85% R = 7-Me, 78% R = 7-Br,
83% 70%
R = 6-Me,
82% R = 6-Cl,
62%
N
Ph
O 77% N
O
O
R'
83% R = 4-MeOC6H4, 84% R = 4-ClC6H4,
86% 85%
R = 4-BrC6H4,
75% R = 4-CF3C6H4,
75%
R = 4-CF3C6H4,
75% R = CO2Et,
90%
Ph
O
X
R'
83%
R = Ph, R = 4-FC6H4,
MeO2C
O
N R
Ag2CO3(3 equiv), C6H6, 170 C
Ph R = 6-Br,
O
R
.
O
N R
N O 90%
O Ph
N S 60%
O Ph
R' = 4-MeOC6H4, R' = 4-FC6H4, R' = 4-BrC6H4,
86% 79% 72%
R' = 4-MeC6H4, 70% R' = 4-ClC6H4, 95% R' = 4-CF3C6H4, 72%
R' = 3-MeOC6H4, R' = 3-FC6H4, R' = 3-BrC6H4,
70% 71% 87%
R' = 3-MeC6H4, R' = 3-ClC6H4, R' = 3-CF3C6H4,
R' = 3,4-2ClC6H4,
95%
R' = 3-thienyl,
78% 93% 91% 39%
Scheme 41
Page 202
©
ARKAT-USA, Inc
Reviews and Accounts
ARKIVOC 2015 (i) 184-211
4. Csp3-H Bond Functionalizations Direct functionalization of unactivated C(sp3)–H bond has been a focal point of experimental and theoretical research and play important roles among these synthesis routes. In recent year, more attention has been paid to the development of nickel catalysis directly catalyse C(sp3)–H functionalization and achieve some challenging research results. Catalytic asymmetric cross-dehydrogenative coupling reaction (CDC reaction) has attracted great attention because it provides efficient methods to construct versatile and useful building blocks.67-73 Under oxidative conditions, two C–H bonds could be directly coupled to form a new C– C bond without prior installation of functional groups. In 2013, Feng group74 developed catalytic asymmetric cross-dehydrogenative coupling of β-ketoesters and xanthene using a cooperative bimetallic catalyst system (Scheme 42). Various optically active xanthene derivatives bearing a quaternary stereogenic carbon center were obtained in up to 90% yields with up to 99% ee under mild conditions.
R1
O CO2R2
.
O
NiBr2/Fe(BF4)2 H2O/L2
CO2R2 +
(10 mol%, 1.0:2:1.2)
R1 O
tBuOOH
O
CHCl2CHCl2, 30 °C
R1= H, Me, F, Br, Cl
up to 95% yield up to 95% ee
R2 = t-Bu, admantyl N O
N O
Ar
O Ar = 2,3-iPr2C6H3
O
N H
H N Ar
Scheme 42 Lei and coworkers75 demonstrated the nickel-catalyzed oxidative arylation of C(sp3)-H bonds in moderate to good yield (Scheme 43-45). Several substituted arylboronic acids and various C(sp3)-H bonds were approved to be suitable substrates for this novel transformation. This process provides an effective method for the introduction of simple ether derivatives to synthese α-arylated ethers. Preliminary mechanistic studies suggest that this reaction possiblly proceed through a radical pathway. [Ni(acac)2] (10 mol%) PPh3 (10 mol%) Ar B(OH)2 + H
Ar
O
Ar
K3PO4 (1.0 equiv) DTBP (1.0 equiv) 100 °C, 16 h
Yield(%)
Ar
O
Yield(%)
Ph 88 4-CH3COC6H4 78
4-MeOC6H4 4-CF3C6H4
93 52
4-FC6H4 2-CH3C6H4
4-ClC6H4 nathph-2-yl
84 52
86 84
Scheme 43
Page 203
©
ARKAT-USA, Inc
Reviews and Accounts
ARKIVOC 2015 (i) 184-211 [Ni(acac)2] (10 mol%) Ar B(OH)2 + H
Ar
PPh3 (10 mol%)
O
O
Ar K3PO4 (1.0 equiv) DTBP (1.0 equiv) O 100 °C, 16 h Yield(%) Ar Yield(%)
Ph 63 4-CH3OCOC6H4 57 3-CH3OC6H4 50
4-CNC6H4 3-CH3C6H4 2-CH3C6H4
O
70 64 52
Scheme 44
B(OH)2
3
+ H R(Csp )
O
N
O 53%
71%
[Ni(acac)2] (10 mol%) PPh3 (10 mol%)
R(Csp3)
K3PO4 (1.0 equiv) DTBP (1.0 equiv) 100 °C, 16 h N
N
O 56%
45%
Scheme 45 In 2014, You76 disclosed the nickel-catalyzed unactivated β-C(sp3)–H bond arylation of aliphatic acid derivatives with aryl iodides/bromides via bidentate chelation-assistance of an 8aminoquinoline moiety (Scheme 46). These preliminary results in the reaction indicate the intrinsic catalytic potential of nickel metal for unactivated C(sp3)–H bond arylation. Ge77 developed a a nickel-catalyzed sp3 C-H bond functionalization process for site-selective intramolecular dehydrogenative cyclization reaction of 2,2-disubstituted propionamides (Scheme 47). The reaction suits to the C-H bonds of β-methyl groups over the γ-methyl or β-methylene groups. Additionally, a predominant preference for the β-methyl C-H bonds over the aromatic sp2 C-H bonds was observed. Moreover, this process also allows for the effective functionalization of benzylic secondary sp3 C-H bonds. Naoto78 still reported the similar studies on the direct arylation of C-(sp3)−H (methyl and methylene) bonds in aliphatic amides containing an 8-aminoquinoline moiety as a bidentate directing group with aryl halides catalyzed by Ni catalysis. O R1 R2
N H H
+ N
Ni(OTf)2 (10 mol%), PPh3 (20 mol%)
X R
DMSO (3.5 equiv)/PivOH(0.2 equiv) -
Na2CO3 (2.0 eauiv), 1,4 dioxane 160 °C, 36 h
R1, R2 = H, alkyl, aryl, alkenyl R = 4-MeO, 2-MeO, 4-NH2, 3-MeO, 4-AcNH 4-CH3CO, 4-CO2Me, 4-CO2NEt2 X = Br, I
O R1 R2
N H
N R
35-83% yield
Scheme 46
Page 204
©
ARKAT-USA, Inc
Reviews and Accounts
ARKIVOC 2015 (i) 184-211
1O nR
N H
R2 R3
[Ni(dme)2I2] (20 mol%) TEMPO (3 equiv) K2HPO4 (2 equiv), TBAI (0.1equiv)
Q
O R1
n
nPrCN/PhCN, 150 °C, 24 h
Q=
N Q
2
N
R
R3
H
R1,R2 = nPr, Et; 85% R1,R2 = Me, Me; 91% R1,R2 = Et, Et; 85% R1,R2 = nPr, nPr; 81% R1,R2 = Me, PhCO2CH2; 90% R1,R2 = Et, C5H11; 81% O R1,R2 = Et, PhCH2CH2; 82% R1,R2 = Me, CF3; 93% N Q R1,R2 = Me, AcOCH2; 86% R1,R2 = Et, Me; 90%
R1 R2
1
2
1
O
2
R ,R = Ph, Me; 92% R ,R = Ph, Et; 85% R1,R2 = Ph, nPr; 83% R1,R2 = Ph, Et; 85%
n
R1,R2 = Me, Bn; 82% R1,R2 = Et, Bn; 72% R1,R2 = Me, Me R3 = Ph; 7%
O R1 N Q
R2
R3
O
R1,R2 = Et, Me R3 = Ph; 11% O
R1,R2 = Et, Et R3 = 4-ClC6H4; 75% R1,R2 = Et, Et R3 = 3-BrC6H4; 68% R1,R2 = Et, Et R3 = 1-naphthyl; 64%
n = 1; 57%
N Q n = 2; 74% n = 3; 70% Ph OMe
n
R1,R2 = Et, Et R3 = Ph; 73% R1,R2 = Et, Et R3 = 4-MeC6H4; 70%
n = 1; 65% N Q n = 2; 81% n = 3; 79%
N N 87%
Ph
Scheme 47 In 2014, Gartia et al79 described the catalytic coupling of Grignard reagents with the C–H bond of oxygen containing heterocyclic compounds such as tetrahydrofuran catalysed by nickel(II) complex (Scheme 48). The nickel(II) complex showed excellent activity in catalyzing C–H activation and further coupling with various Grignard reagents. The effective activation of the C–H bond proceeded under ambient reaction conditions with a short reaction time (1–2 h) and catalyst loading as low as 0.01 mol%. This catalytic route could prove to be an efficient method for the preparation of synthetically and pharmaceutically relevant molecules by activation of sp3 C–H bonds in various heterocycles.
Li+ n
O n = 1, 2
or O
+ RMgX
hterocycle including oxygen R = aryl, alkyl,allyl
O iPr
O iPr Ni Cl iPr
i Pr
(0.01-0.02 mol%) 25 °C, air , 1 h BrCH2CH2Br (3-5 equiv)
n
O
R
or O
R
Up to 92% yield
Scheme 48
5 Conclusions Over the past decades, there has been an explosive growth in the development of methods for C–H functionalization and the application of these technologies for the synthesis of complex targets such Page 205
©
ARKAT-USA, Inc
Reviews and Accounts
ARKIVOC 2015 (i) 184-211
as natural products and pharmaceutical agents. Various nickel salts or complexes are extensively used as catalyst for these reactions due to their high efficiency and low cost. This review presented an overview of the area of nickel-catalyzed direct C–H bond functionalizations and C−C bond forming reactions via Csp–H, Csp2–H and Csp3–H bond activation. Nickel-catalyzed C-H bond functionalized reactions which lead to the formation of C–C bonds have been recognized as one of important strategies in synthetic organic chemistry. Some important breakthroughs in the study of nickel-catalyzed direct C-H activations demonstrated that Nickel-catalyzed reactions are broadly applicable to a variety of research fields related to organic synthesis. Important developments have come true to extend the substrate scope, particularly, including simple arenes, electron-deficient aromatic and heteroaromatic substrates. From a synthetic point of view, nickel-catalyzed direct C–H bond functionalizations provide novel and efficient tools for constructing various useful compounds. Gathering mechanistic insights could help us to understand the nature of these reactions and lead to the discovery of unique reactivities of metal catalysts. However, there are still some major challenges that need to be addressed in this rapidly developing area. Most mechanisms proposed in this study are preliminary methods lacking solid and thorough experimental and theoretical studies. Moreover, only a few reactions with chiral ligands could realize asymmetric catalysis. Enantioselective C−H functionalization and C(sp3)−H functionalization may represent significant challenges for further catalyst/reaction developments, etc. To overcome these central challenges, an increasing demand for the robust catalytic systems will continue to drive the field forward towards the development of ideal C–H bond activation. With increased exploitation of nickel catalysts, new exciting and innovative achievements are expected to appear in the near future.
Acknowledgements We thank the National Natural Science Foundation of China (21362005), the Natural Science Foundation of the Guizhou Science and Technology Department (JZ[2014]2010) and The Science and Technology Planning Project of Guiyang city [(2012204)23] for financial support.
References 1. Sun, C. –L.; Li, B. –J.; Shi, Z. -J. Chem. Rev. 2011, 111, 1293. http://dx.doi.org/10.1021/cr100198w 2. Zhang, S. –Y.; Zhang, F. –M.; Tu, Y. –Q. Chem. Soc. Rev. 2011, 40, 1937. http://dx.doi.org/10.1039/c0cs00063a 3. Collet, F.; Lescot, C. Dauban, P. Chem. Soc. Rev. 2011, 40, 1926. http://dx.doi.org/10.1039/c0cs00095g 4. Boorman, T. C.; Larrosa, I. Chem. Soc. Rev. 2011, 40, 1910. http://dx.doi.org/10.1039/c0cs00098a Page 206
©
ARKAT-USA, Inc
Reviews and Accounts
ARKIVOC 2015 (i) 184-211
5. Che, C. –M.; Lo, K –Y.; Zhou, C. –Y. and Huang, J. -S. Chem. Soc. Rev. 2011, 40, 1950. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25.
http://dx.doi.org/10.1039/c0cs00142b Li, H.; Lia, B.-J.; Shi, Z. –J. Catal. Sci. Technol. 2011, 1, 191. http://dx.doi.org/10.1039/c0cy00076k McMurray, L.; ÓHara, F.; Gaunt, M. J. Chem. Soc. Rev. 2011, 40, 1885. http://dx.doi.org/10.1039/c1cs15013h Giri, R.; Shi, B. -F.; Engle, K. M.; Maugel, N.; Yu, J. -Q. Chem. Soc. Rev. 2009, 38, 3242. http://dx.doi.org/10.1039/b816707a Ackermann, L.; Vicente, R.; Kapdi, R. Angew. Chem. Int. Ed. 2009, 48, 9792. http://dx.doi.org/10.1002/anie.200902996 Doyle, M. P.; Duffy, R.; Ratnikov, M.; Zhou, L. Chem. Rev. 2010, 110, 704. http://dx.doi.org/10.1021/cr900239n Collet, F.; Lescot, C.; Dauban, P. Chem. Soc. Rev. 2011, 40, 1926. http://dx.doi.org/10.1039/c0cs00095g Borovik, A. S. Chem. Soc. Rev. 2011, 40, 1870. http://dx.doi.org/10.1039/c0cs00165a Gutekunst, W. R.; Baran, P. S. Chem. Soc. Rev. 2011, 40, 1976. http://dx.doi.org/10.1039/c0cs00182a Wencel-Delord, J.; Dröge, T.; Liu, F.; Glorius, F. Chem. Soc. Rev. 2011, 40, 4740. http://dx.doi.org/10.1039/c1cs15083a Cho, S. H.; Kim, J. Y.; Kwak, J.; Chang, S. Chem. Soc. Rev. 2011, 40, 5068. http://dx.doi.org/10.1039/c1cs15082k Yan, G. B., Wu, X. M.; Yang. M. H. Org. Biomol. Chem. 2013, 11, 5558. http://dx.doi.org/10.1039/c3ob40652k Yang, L.; Huang, H. M. Catal. Sci. Technol. 2012, 2, 1099. http://dx.doi.org/10.1039/c2cy20111a Dick, A. R.; Sanford, M. S. Tetrahedron 2006, 62, 2439. http://dx.doi.org/10.1016/j.tet.2005.11.027 Gaillard, S.; Cazin, C. S. J.; Nolan, S. P. Acc. Chem, Res. 2012, 45, 778. http://dx.doi.org/10.1021/ar200188f Tang, S. Y.; Gong T. J.; Fu, Y. Sci. Chin. Chem. 2013, 56, 619. http://dx.doi.org/10.1007/s11426-012-4795-3 Song W. F. Ph. D. thesis “Cobalt- and nickel-catalyzed functionalization of unactivated C-hal, C-O and C-H bonds”. Göttingen, Georg-August-Universität Göttingen, 2013. Tasker, S. Z.; Stan, E. A.; Jamisondley, T. F. Nature 2014, 509, 299. http://dx.doi.org/10.1038/nature13274 Samai, S.; Nandi, G. C.; Singh, M. S. Tetrahedron Lett. 2010, 51, 5555. http://dx.doi.org/10.1016/j.tetlet.2010.08.043 Liang, L.-C.; Chien, P.–S. Huang, Y.–L. J. Am. Chem. Soc. 2006, 128, 15562. http://dx.doi.org/10.1021/ja065505p Muto, K.; Yamaguchi, J.; Lei, A.; Itami, K. J. Am. Chem. Soc. 2013, 135, 16384. Page 207
©
ARKAT-USA, Inc
Reviews and Accounts
26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42.
43. 44.
ARKIVOC 2015 (i) 184-211
http://dx.doi.org/10.1021/ja409803x Miyazaki, Y.; Yamada, Y.; Nakao, Y.; Hiyama, T. Chem. Lett. 2012, 41, 298. http://dx.doi.org/10.1246/cl.2012.298 Nakao, Y.; Morita, E.; Idei, H.; Hiyama, T. J. Am. Chem. Soc. 2011, 133, 3264. http://dx.doi.org/10.1021/ja1102037 Nakao, Y.; Idei, H.; Kanviya, K. S.; Hiyama, T. J. Am. Chem. Soc. 2009, 131, 5070. http://dx.doi.org/10.1021/ja901153s Nakao, Y.; Kanyiva, K. S.; Hiyama, T. J. Am. Chem. Soc. 2008, 130, 2448. http://dx.doi.org/10.1021/ja710766j Y. Nakao, H. Idei, K. S. Kanyiva, T. Hiyama, J. Am. Chem. Soc. 2009, 131, 15996. http://dx.doi.org/10.1021/ja907214t Kumar, P.; Louie, J. Angew. Chem. Int. Ed. 2011, 50, 10768. http://dx.doi.org/10.1002/anie.201103621 Dupont, J.; Consorti, C.; Spencer, S. J. Chem. Rev. 2005, 105, 2527. http://dx.doi.org/10.1021/cr030681r Albrecht, M. Chem. Rev. 2010, 110, 576. http://dx.doi.org/10.1021/cr900279a Lyons,T. W.; Sanford, M. S. Chem. Rev. 2010, 110, 1147. http://dx.doi.org/10.1021/cr900184e Carmona, E.; Palma, P.; Paneque, M.; Poveda, M. L. J. Am. Chem. Soc. 1986, 108, 6424. http://dx.doi.org/10.1021/ja00280a070 Carmona, E. And Gutierrez-Puebla, E. Polyhedron, 1989, 8, 1069. http://dx.doi.org/10.1016/S0277-5387(00)81121-3 Tekavec, T. N.; Louie, J. Tetrahedron 2008, 64, 6870. http://dx.doi.org/10.1016/j.tet.2008.03.071 Yoshida, Y.; Kurahashi, T.; Matsubara, S. Chem. Lett. 2012, 41, 1498. http://dx.doi.org/10.1246/cl.2012.1498 Ogata, K.; Atsuumi, Y. Shimada, D.; Fukuzawa, S. Angew. Chem. Int. Ed. 2011, 50, 5896. http://dx.doi.org/10.1002/anie.201101468 Yoshinori, A.; Naoto, C. J. Am. Chem. Soc. 2013, 135, 5308. http://dx.doi.org/10.1021/ja401344e Nakao,Y.; Kashihara, N.; Kanyiva, K. S.; Hiyama, T. J. Am. Chem. Soc. 2008, 130, 16170. http://dx.doi.org/10.1021/ja807258m Doster, M. E.; Hatnean, J.; A. Jeftic, T.; Modi, S.; Johnson, S. A. J. Am. Chem. Soc. 2010, 132, 11923. http://dx.doi.org/10.1021/ja105588v Xie, G. L.; Li, T. Y.; Qu, X. M.; Mao, J. C. J Mol.Catal. A. Chem. 2011, 340, 48. http://dx.doi.org/10.1016/j.molcata.2011.03.007 Shiota, H.; Ano, Y.; Aihara, Y.; Fukumoto, Y.; Chatani, N. J. Am. Chem. Soc. 2011, 133, 14952. http://dx.doi.org/10.1021/ja206850s Page 208
©
ARKAT-USA, Inc
Reviews and Accounts
ARKIVOC 2015 (i) 184-211
45. Liu, C.; Liu, D.; Zhang, W. Zhou, L. L.; Lei, A. W. Org. Lett. 2013, 15, 6166. 46. 47.
48. 49. 50.
51. 52.
53. 54.
55.
56. 57. 58. 59. 60.
61. 62.
http://dx.doi.org/10.1021/ol403021p Nakao, Y Yamada, Y.; Kashihara, N.; Hiyama, T. J. Am. Chem. Soc. 2010, 132, 13666. http://dx.doi.org/10.1021/ja106514b Xi, N.; Huang, Q.; Liu, L.. In Comprehensive Heterocyclic Chemistry III; Katritzky, A. R., Ramsden, C. A., Scriven, E. F. V., Taylor, R., Eds.; Elsevier: Oxford, 2008; Vol. 4, pp 143. http://dx.doi.org/10.1016/B978-008044992-0.00402-8 Kanyiva, K. S.; Löermann, F.; Nakao, Y.; Hiyama. T. Tetrahedron Lett. 2009, 50, 3463. http://dx.doi.org/10.1016/j.tetlet.2009.02.195 Nakao, Y.; Kashihara, N.; Kanyiva, K. S.; Hiyama, T. Angew. Chem. Int. Ed. 2010, 49, 4451. http://dx.doi.org/10.1002/anie.201001470 Casalnuovo, A. L.; Rajanbabu,T. V.; Ayers,T. A.; Warren, T. H. J. Am. Chem. Soc. 1994, 116, 9869. http://dx.doi.org/10.1021/ja00101a007 Shirakura, M.; Suginome, M. Org. Lett. 2009, 11, 523. http://dx.doi.org/10.1021/ol802475h Qu, G. -R.; Xin, P. -Y.; Niu, H. -Y.; Wang, D. -C.; Ding, R. -F.; Guo, H. -M. Chem. Commun. 2011, 47, 11140. http://dx.doi.org/10.1039/c1cc14558d Muto, K.; Yamaguchi, J.; Itami, K. J. Am. Chem. Soc. 2012, 134, 169. http://dx.doi.org/10.1021/ja210249h Iaroshenko, V. O., Ali, I.; Mkrtchyan, S.; Sementuchenko, V.; Ostrovskyi, D.; Langer, P. Synlett 2012, 18, 2603. http://dx.doi.org/10.1055/s-0032-1317329 Xin, P. -Y.; Niu, H. -Y.; Qu, G. -R.; Ding, R. -F.; Guo, H. -M. Chem. Commun. 2012, 48, 6717– 6719. http://dx.doi.org/10.1039/c2cc32396f Muto, K.; Yamaguchi, J.; Itami, K. J. Am. Chem. Soc. 2012, 134, 169. http://dx.doi.org/10.1039/c2cc32396f lvarez-Bercedo, P.; Martin, R. J. Am. Chem. Soc. 2010, 132, 17352. Tobisu, M.; Shimasaki, T.; Chatani, N. Angew. Chem. Int. Ed. 2008, 47, 4866. http://dx.doi.org/10.1002/anie.200801447 Tobisu, M.; Shimasaki, T.; Chatani, N. Chem. Lett. 2009, 38, 710. http://dx.doi.org/10.1246/cl.2009.710 Guan, B. -T.; Xiang, S. -K.; Wang, B. -Q.; Sun, Z. -P.; Wang, Y.; Zhao, K. -Q.; Shi, Z. -J. J. Am. Chem. Soc. 2008, 130, 3268. http://dx.doi.org/10.1021/ja710944j Amaike, K.; Muto, K.; Yamaguchi, J.; Itami, K. J. Am. Chem. Soc. 2012, 134, 13573. http://dx.doi.org/10.1021/ja306062c Correa, A.; Cornella, J.; Martin, R. Angew. Chem. Int. Ed. 2013, 52, 1878. http://dx.doi.org/10.1002/anie.201208843 Page 209
©
ARKAT-USA, Inc
Reviews and Accounts
ARKIVOC 2015 (i) 184-211
63. Beletskaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000, 100, 3009. 64.
65.
66. 67. 68.
69. 70. 71. 72. 73. 74.
75. 76.
77. 78. 79.
http://dx.doi.org/10.1021/cr9903048 Meng, L.; Kamada, Y.; Muto, K.; Yamaguchi, J.; Itami. K. C. -H Angew. Chem. Int. Ed. 2013, 52, 10048. http://dx.doi.org/10.1002/anie.201304492 Nett, M.; Erol, Ö.; Kehraus, S.; Kock, M.; Krick, A.; Eguereva, E.; Neu, E.; Kçnig, G. M. Angew. Chem. Int. Ed. 2006, 45, 3863. http://dx.doi.org/10.1002/anie.200504525 Yang, K.; Zhang, C.; Wang, P.; Zhang, Y.; Ge, H. B. Chem. Eur. J. 2014, 20, 7241. http://dx.doi.org/10.1002/chem.201402516 Li, Z.; Bohle, D. S.; Li, C. -J. Proc. Natl. Acad. Sci. U. S. A. 2006, 103, 8928. http://dx.doi.org/10.1073/pnas.0601687103 Caron, S.; Dugger, R. W.; Ruggeri, S. G.; Ragan, J. A.; Ripin, D. H. B. Chem. Rev. 2006, 106, 2943. http://dx.doi.org/10.1021/cr040679f Klussmann, M.; Sureshkumar, D. Synthesis 2011, 353. http://dx.doi.org/10.1055/s-0030-1258303 Yeung, C. S.; Dong, V. M. Chem. Rev. 2011, 111, 1215. http://dx.doi.org/10.1021/cr100280d Liu, C.; Zhang, H.; Shi, W.; Lei, A. Chem. Rev. 2011, 111, 1780. http://dx.doi.org/10.1021/cr100379j Shi, W.; Liu, C.; Lei, A. Chem. Soc. Rev. 2011, 40, 2761. http://dx.doi.org/10.1039/c0cs00125b Wendlandt, A. E.; Suess, A. M.; Stahl, S. S. Angew.Chem. Int. Ed. 2011, 50, 11062. http://dx.doi.org/10.1002/anie.201103945 Cao, W. D.; Liu, X. H.; Peng, R. X.; He, P.; Lin, L. L.; Feng, X. M. Chem. Commun. 2013, 49, 3470. http://dx.doi.org/10.1039/c3cc41315b Liu, D.; Liu, C.; Li, H. and Lei, A. W. Angew. Chem. Int. Ed. 2013, 52, 4453. http://dx.doi.org/10.1002/anie.201300459 Li, M. L.; Dong, J. X.; Huang, X. L.; Li, K. Z.; Wu, Q.; Song, F. J.; You, J. S. Chem. Commun. 2014, 50, 3944. http://dx.doi.org/10.1039/c4cc00716f Wu, X. S.; Zhao, Y.; Ge, H. B. Chem. Eur. J. 2014, 20, 9530. http://dx.doi.org/10.1002/chem.201403356 Aihara, Y. and Chatani, N. J. Am. Chem. Soc. 2014, 136, 898. http://dx.doi.org/10.1021/ja411715v Gartia, Y.; Ramidi, P.; Jones, D. E.; Pulla, S.; Ghosh, A. Catal. Lett. 2014, 144, 507. http://dx.doi.org/10.1007/s10562-013-1170-8
Page 210
©
ARKAT-USA, Inc
Reviews and Accounts
ARKIVOC 2015 (i) 184-211
Authors' Biographies
Xiao-hua Cai was born in 1966. He graduated at Shaoyang Technology University, China, in 1988. He received his M.S. in chemistry from Xi’an Modern Chemistry Research Institute in 1999, and his Ph.D in sciences from Graduate School of the Chinese Academy of Sciences in 2005. He became a professor at College of Chemistry and environmental Science, Guizhou Minzu University in 2006. Her current research interests cover asymmetric catalysis and organic synthesis and bioactivity of natural products.
Jun Jin was born in Guizhou, China, in 1993. He received his Bachelor degree in 2013 from the Guizhou Minzu University, Guiyang. He is currently a third-year masterate candidate at the Guizhou Minzu University, focusing on organic reactions.
Page 211
©
ARKAT-USA, Inc
