Rhodium(III)-Catalyzed Controllable C?H Bond Functionalization of Benzamides and Vinylidenecyclopropanes: A Directing Group Determined Reaction Pathway

Article abstract of DOI:10.1002/adsc.201601308

A controllable rhodium(III)-catalyzed C?H bond activation of benzamides and vinylidenecyclopropanes (VDCPs) by changing the directing group from C(O)NH–OPiv to C(O)NH–OBoc has been disclosed, affording two different major products in good yields under mild condition, respectively. The substrate scope has been investigated and a plausible reaction mechanism has been also proposed on the basis of previous literature. (Figure presented.).

Full text of DOI:10.1002/adsc.201601308

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DOI: 10.1002/adsc.201601308
À
Rhodium(III)-Catalyzed Controllable C H Bond Functionaliza-
tion of Benzamides and Vinylidenecyclopropanes: A Directing
Group Determined Reaction Pathway
Cheng Ji,a Qin Xu,a and Min Shia,b,c,
*
a
Key Laboratory for Advanced Materials and Institute of Fine Chemicals, School of Chemistry & Molecular Engineering,
East China University of Science and Technology, 130 Mei Long Road, Shanghai 200237, Peopleꢀs Republic of China
State Key Laboratory and Institute of Elemento-organic Chemistry, Nankai University, Tianjin 300071, Peopleꢀs Republic
of China
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
Sciences, 354 Fenglin Lu, Shanghai 200032, Peopleꢀs Republic of China
b
c
Fax : (+86)-21-6416-6128; e-mail: mshi@mail.sioc.ac.cn
Received: November 27, 2016; Revised: January 2, 2017; Published online: && &&, 0000
Supporting information for this article is available under http://dx.doi.org/10.1002/adsc.201601308.
À
Abstract: A controllable rhodium(III)-catalyzed C
H bond activation of benzamides and vinylidenecy- posed on the basis of previous literature.
clopropanes (VDCPs) by changing the directing
a plausible reaction mechanism has been also pro-
group from C(O)NH–OPiv to C(O)NH–OBoc has
been disclosed, affording two different major prod- Keywords: allenes; benzamides; C H bond activa-
ucts in good yields under mild condition, respective- tion; directing groups; rhodium(III)-catalyzed pro-
ly. The substrate scope has been investigated and cess; vinylidenecyclopropanes
À
Introduction
With the aid of allenes, scientists can rapidly generate
complex molecular structures from easily accessible
À
During the past decades, C H bond functionalizations starting materials under mild reaction conditions. De-
have emerged as a powerful tool in organic synthe- spite the significance of allenes in organic chemistry,
sis.[1] Great progress has been made in transition the role of allenes is limited in transition metal-cata-
metal-catalyzed C H bond functionalization for lyzed C H bond functionalization. In 2012, Glorius
building various C–C and C X bonds, and has afford- reported the annulative coupling between benzimides
À
À
À
ed a streamlined and step-economical method for and allenes [Scheme 1, Eq. (1)].[10] After that, Ma re-
building desired valuable heterocycles without pre-ac- ported the ortho-allylation of N-methoxybenzamides
tivation of the coupling partner.[2] In addition to the with polysubstituted allenes [Scheme 1, Eq. (2)].[11] In
widely explored C–H activation/functionalization re- 2013, Cramer reported the first enantioselective ally-
actions catalyzed by transition metals such as Pd, Ru, lation of N-methoxybenzamides with polysubstituted
and Cu, Rh(III) complexes have been well-recognized allenes [Scheme 1, Eq. (3)].[11c] In the same year,
as catalysts for C–H activation.[3] Rh(III)-catalyzed Rh(III)-catalyzed C–H activation was applied to the
C–H activation stands out with high activity, broad synthesis of functionalized allenes [Scheme 1, Eqs. (4)
substrate scope, high functional group tolerance and and (5)] by the group of Ma.[12]
mild condition. Rh(III)-catalyzed synthesis of nitro-
In these reactions, the directing groups played a sig-
À
gen-containing unsaturated heterocycles can be ac- nificant role in C H bond functionalizations. In gen-
cessed through coupling of amides, amines, oximes, eral, the functional groups C(O)NH–OMe and
and anilines with alkynes to access isoquinolones,[4] C(O)NH–OPiv were used quite often in this aspect.
pyridones,[5] isoquinolines,[6] pydridines,[7] indoles,[8] In any sense, the directing groups can determine the
and pyrroles.[9]
reaction pathway to give different products. For ex-
Over the past decades, the synthesis of allenes has ample, in 2011, Glorius reported the first example of
made significant progress and a large number of the reaction of benzamides and olefins, in which
useful and practical methods have been explored. C(O)NH–OMe underwent b-hydride elimination to
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tion products on the basis of different directing
groups are rare.[14]
Results and Discussion
À
In this contribution, we report controllable C H bond
functionalizations of benzamides and vinylidenecyclo-
propanes (VDCPs) through changing the directing
group from C(O)NH–OPiv to C(O)NH–OBoc, af-
fording different major products 3 and 4 under mild
conditions, respectively.
We initially started our investigation by examining
the reaction outcomes of benzamide 1a (1.0 equiv.)
and VDCP 2a (1.2 equiv.) in MeOH in the presence
of [Cp*RhCl2]2 at room temperature and the results
are summarized in Table 1. To our delight, the corre-
sponding products 3a and 4a were formed in 82%
total yield along with the product ratio of 3:1
(Table 1, entry 1). To improve the yield of a, we per-
formed this reaction by changing the additive, solvent,
ratio of reactants and reaction temperature (Table 1).
We found that utilization of CF3CH2OH[15] instead of
MeOH as the solvent did not improve the yield of 3a
and 4a as well as their ratio (Table 1, entry 2). On
raising the reaction temperature to 30 or 508C, no im-
provements were observed (Table 1, entries 3 and 4).
[CP*RhCl2]2 is essential for this reaction because
when using [(p-cymene)RuCl2]2, [Cp*RuCl2]2 and
[Cp*IrCl2]2 as catalysts,[16a–i] no reaction occurred or
only traces of 3a and 4a were afforded upon heating
at 508C in the presence of [Cp*RuCl2]2 (Table 1, en-
tries 5–10). Using Cp*Rh(MeCN)3(SbF6)2 as the cata-
lyst did not bring any beneficial effect to the reaction
outcome (Table 1, entry 11). Changing the employed
amount of 1a did not give better results as well
(Table 1, entries 12 and 13). Next, CsF (1.0 equiv.)
was added to improve the reaction outcome,[16j,k]
giving 3a and 4a in 94% total yield along with the
product ratio of 3:1 at room temperature (Table 1,
entry 14). When the reaction was carried out at 08C,
the products 3a and 4a were formed in 92% total
yield along with the product ratio of 4:1 (Table 1,
entry 15). On adding CsF, the total yield of 3a and 4a
reached up to 99% along with the product ratio of 5:1
(Table 1, entry 16). The use of PivOH instead of CsF
did not further improve the yield of 3a and 4a
Scheme 1. Rh(III)-catalyzed C–H functionalization involving
allenes and our work.
give acyclic olefins, but C(O)NH–OPiv proceeded (Table 1, entry 17). We identified that the optimized
through reductive elimination to give cyclic benzam- reaction conditions are use of [Cp*RhCl2]2
ACHTUNGTRENNUNG
ides.[13a] After that, Sun and co-workers reported dif- (3.0 mol%) as the catalyst, CsOAc as base, CsF as ad-
ferent outcomes in the reaction of benzamides with ditive and carrying out the reaction in MeOH
methylenecyclopropanes (MCPs), in which the prod- (2.0 mL) at 08C for 36 h (Table 1, entry 16) (for more
uct selectivity depended on the aromatic rings and re- detailed information, see the Supporting Informa-
action temperature[13c] (a benzene ring gave [4+2] cy- tion).
cloadducts, but furan and thiophene produced [4+3]
Having the optimized conditions in hand, the scope
cycloadducts). However, the reports with regard to of benzamides bearing diverse substituents on the ar-
À
the selective production of C H bond functionaliza- omatic ring was examined and the results are shown
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Table 1. Optimization of the reaction conditions of benzamides and VDCPs toward the synthesis of 3a.
[a]
The reactions were carried out using 1a (0.2 mmol), 2a (0.7–2.0 equiv.), Cat. (0.006 mmol), in the indicated solvent
(2.0 mL) in a Schlenk tube at the indicated temperature.
Determined by H NMR spectroscopic data.
Isolated yields.
[b]
[c]
1
in Table 2. As for various benzamides 1a–1l having to 2.7:1 product ratios of 3 and 4. In conclusion, sub-
either electron-donating or electron-withdrawing strates with electron-donating groups on the aromatic
groups on the aromatic rings, we found that the sub- rings favored the production of 3.
stituents on the aromatic rings did not have a signifi-
To further evaluate the generality of this reaction,
cant impact on the reaction outcomes, giving the de- the scope of vinylidenecyclopropanes (VDCPs) was
sired products 3a–3l in 57–85% yields. When R=2- then examined (Table 3). VDCP 2b having two gem-
MeC6H4 and 3-MeC6H4, the corresponding products substituted ester groups on the cyclopropyl ring gave
4c and 4d could not be detected, respectively, perhaps the desired product 3m in high yield (91%) without
due to the steric effect. As for substrates 1b, 1e and the formation of 4m. VDCPs with methyl, ethyl, iso-
1f, in which R=4-MeC6H4, 4-MeOC6H4, or 4-t- propyl groups at the allenyl moiety were also tolerat-
BuC6H4, the reactions took place smoothly to afford ed, affording the desired products 3n, 3o and 3p in
the desired products 3b, 3e and 3f in 72–83% yields 68–78% yields along with 2.3:1 to 5.6:1 product ratios
along with better product ratio of 3 and 4 (^3:1). In of 3 and 4. A wide range of substituents on the aro-
the cases of the substrates 1g and 1h bearing strongly matic ring of VDCPs was compatible. For example,
electron-withdrawing groups, such as NO2 or CF3, the halogen-substituted VDCPs were applicable in this
reactions took place efficiently with this catalytic transformation and the reactions proceeded very well
system, giving the desired products 3g and 3h in 57% to furnish the corresponding products 3q, 3r and 3s in
and 73% yields, respectively, also along with the for- moderate yields and 3.1:1 to 3.8:1 product ratios.
mation of 4g and 4h. With substrates 1i–1l, in which Upon introduction of electron-donating groups such
R=4-ClC6H4, 4-BrC6H4, 4-IC6H4, and 4-CNC6H4, the as methyl and tertiary butyl on the phenyl ring,
reactions proceeded also very well to afford the de- VDCPs 2 gave the desired products 3t, 3u and 3v in
sired products 3i–3l in 54–67% yields along with 1.9:1 high yields along with 3.3:1 to 4.9:1 product ratios.
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Table 2. Reaction scope of benzamides for the synthesis of 3.[a,b]
[a]
Isolated yields are given, reaction conditions: 1 (0.2 mml), 2a (0.4 mmol), [Cp*RhCl2]2 (3.0 mol%), CsOAc (0.2 mmol),
CsF (0.2 mmol), MeOH (2.0 mL), 08C, under an argon atmosphere.
Conducted at À108C for 16 h.
[b]
Table 3. Reaction scope of VDCPs toward the synthesis of 3.[a,b]
[a]
Isolated yields are given, reaction conditions: 1a (0.2 mml), 2 (0.4 mmol), [Cp*RhCl2]2 (0.006 mmol), CsOAc (0.2 mmol),
CsF (0.2 mmol), MeOH (2.0 mL), 08C, under an argon atmosphere.
Conducted at À58C for 16 h.
[b]
Non-phenyl group-containing VDCPs, such as those this transformation, affording the desired products 3w
substrates bearing 1-naphthyl and 2-thiopheneyl and 3x in 61% and 67% yields, respectively. The
groups at the allenyl moiety, were also tolerated in structures of 3q and 4q have been unambiguously
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data have been included in the Supporting Informa-
tion.
Interestingly, when the C(O)NH–OPiv directing
group was changed to C(O)NH–OBz, the ratio of 3a
and 4a became to about 1:2 along with 66% total
yield (Table 4, entry 1). To further investigate this
phenomenon and improve the yield and product ratio
of 4a, several directing groups were tested. The results
are demonstrated in Table 4. Substrate 5 reacted with
VDCPs in MeOH at room temperature, giving 3a and
4a in 77% total yield along with a >1:2 product ratio
of 3a and 4a (Table 4, entry 2). On introduction of an
electron-donating group at the benzoyl moiety (X=4-
dimethylaminobenzoyl) the substrate produced 3a
and 4a in 77% total yield along with a >1:1.2 product
Figure 1. X-ray crystal structures of products 3q (left)and 4q
(right).
confirmed by X-ray diffraction. Their ORTEP draw- ratio (Table 4, entry 3). However, on introducing
ings are shown in Figure 1 and the corresponding CIF a strongly electron-withdrawing group at the benzoyl
Table 4. Optimization of the reaction conditions of benzamides with VDCPs toward the
synthesis of 4a.
[a]
The reaction was carried out using 5–9 (0.2 mmol), 2a (0.4 mmol), catalyst (0.006
mmol), in the indicated solvent (2.0 mL) in a Schlenk tube at the indicated tempera-
ture.
Isolated yields.
[b]
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moiety (X=4-triflourmethylbenzoyl or 2,3,4,5,6-pen- 4d was obtained from the ortho-substituted benz-
taflourobenzoyl), the desired products 3a and 4a were amide because of the poor stability of the correspond-
AHCTUNGTRENNUNG
obtained in 73% and 86% yields as well as 1:2.8 and ing benzamide 9 under the standard conditions. Elec-
1:3.1 product ratios, respectively (Table 4, entries 4 tron-deficient benzamides gave the desired product
and 5). Moreover, inspired by Cramer and Fagnouꢀs 4h in 74% yield and a 1:6.2 product ratio was ob-
findings,[17] we also changed the directing group to tained. VDCPs 2 with a methyl, ethyl or isopropyl
C(O)NH–OBoc and found that the reaction of sub- group at the allenyl moiety were also tolerated in this
strate 9 with 2a provided 3a and 4a in 53% yield transformation, giving the desired products 4n, 4o or
along with a 1:6 product ratio (Table 4, entry 6). The 4p in 49–66% yields and 2:1 to 7:1 product ratios.
poor total yield of 3a and 4a was presumably due to Non-phenyl group-containing VDCPs were also com-
the instability of 9 in the presence of CsOAc. Using patible, affording the corresponding products 4w and
PhCOONa as a base, the total yield of 3a and 4a in- 4x in 54–62% yields.
creased to 78% along with a 1:6.1 product ratio,
A plausible mechanism has been depicted in
which was determined as the optimal conditions for Scheme 2 taking substrate 1 or 9 in the reaction with
the production of 4a (Table 4, entry 7).
2a under Cp*Rh(III) catalysis as an example on the
Thus, by changing the directing group to C(O)NH– basis of previous literature reports.[18] Substrate 1 or 9
OBoc, product 4a could be mainly obtained. The gen- reacts with Cp*Rh(III) through direct C–H activation
erality of this transformation was studied as well and to form intermediate I, which is followed by the inser-
the results are shown in Table 5. Electron-rich benz- tion of VDCP 2a to form intermediate II when the di-
ACHTUNGTRENNUNGamides were applicable in this transformation to fur- recting group is C(O)NH–OPiv. Subsequent reductive
À
nish the benzamides 4b and 4f in 63–69% yields and elimination along with internal oxidation leads to C
1:5 to 1:6 product ratios of 3 and 4. Introducing a sub- N bond formation/N O bond cleavage to give 3a
À
stituent at the meta-position of benzamide gave the along with the regeneration of the Rh(III) catalyst to
desired product 4c in 53% yield along with a 1:3.8 start a new catalytic cycle (cycle A). When the direct-
product ratio. However, none of the desired product ing group is C(O)NH–OBoc, the insertion of I with
Table 5. Reaction scope toward the synthesis of 4.[a,b]
[a]
Isolated yields are given, reaction conditions: 9 (0.2 mmol), 2 (0.4 mmol), [Cp*RhCl2]2 (0.006 mmol), CsOAc (0.2 mmol),
MeOH (2.0 mL), room temperature, under an argon atmosphere.
Isolated yields.
[b]
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Scheme 2. Proposed mechanism for the reactions.
2a gives intermediate III, which undergoes N–Rh the directing group from C(O)NH–OPiv to C(O)NH–
bond cleavage to form intermediate IV. Then OBoc, affording two different major products in good
Cp*Rh(III)-catalyzed b-C elimination of cyclopro- yields under mild conditions. A plausible mechanism
pane generates intermediate V, which undergoes N– has been also proposed on the basis of previous litera-
Rh bond reformation to afford intermediate VI. Simi- ture reports and our own examination. Efforts are in
lar reductive elimination and internal oxidation lead progress to apply this new methodology to the synthe-
À
À
to C N bond formation/N O bond cleavage to pro- sis of interesting biologically active compounds.
duce 4a and regenerate the Rh(III) catalyst for the
next catalytic cycle (cycle B, path a). Intermediate III
may also undergo b-C elimination of cyclopropane
generating intermediate VI directly (cycle B, path b).
Considering the rationale of these different reaction
pathways, we believe that the electron-withdrawing
Experimental Section
property and steric effect of N–OBoc make inter-
General Procedure for Synthesis of 3
mediate III more easily undergo a b-C elimination[19]
Under an argon atmosphere, compound 1 (0.2 mmol), 2
(0.4 mmol) [Cp*RhCl2]2 (5.0 mg, 0.06 mmol), CsF (30.4 mg,
0.2 mmol) and CsOAc (38.4 mg, 0.2 mmol) were weighed
into a Schlenk tube. MeOH (2.0 mL) was added and the
mixture was stirred at 08C until compound 1 was consumed
(see the Supporting Information for further informa-
tion).
Conclusion
completely. The reaction mixture was filtered through
Celite. The filtrate was concentrated under the reduced
pressure and the residue was purified by a silica gel column
flash chromatography (eluent: petroleum ether/ethyl ace-
In summary, we have developed a useful and control-
lable C–H functionalization using VDCPs as new sub-
strates with high product selectivity through changing tate=4/1) to afford the product 3.
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General Procedure for Synthesis of 4
Under an argon atmosphere, compound 9 (0.2 mmol), 2
(0.4 mmol) [Cp*RhCl2]2 (3.7 mg, 0.006 mmol) and PhCOO-
Na (8.6 mg, 0.06 mmol) were weighed into a Schlenk tube.
MeOH (2.0 mL) was added and the mixture was stirred at
258C until compound 9 was consumed completely. The reac-
tion mixture was filtered through Celite. The filtrate was
concentrated under the reduced pressure and the residue
was purified by silica gel column flash chromatography
(eluent: petroleum ether/ethyl acetate=2/1) to afford the
product 4.
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Supporting Information Available
Detailed descriptions of experimental procedures and the
spectroscopic data of the products as well as the crystal
structures are presented in the Supporting Information.
CCDC 1436566 (3q) and CCDC 1440757 (4q) contain the
supplementary crystallographic data for this paper.
These data can be obtained free of charge from
The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
Acknowledgements
We are grateful for the financial support from the National
Basic Research Program of China [(973)-2015CB856603],
the Strategic Priority Research Program of the Chinese Acad-
emy of Sciences (Grant No. XDB20000000), and the Nation-
al Natural Science Foundation of China (20472096,
21372241, 21572052, 20672127, 21421091, 21372250,
21121062, 21302203, and 20732008).
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Rhodium(III)-Catalyzed Controllable C H Bond
Functionalization of Benzamides and
Vinylidenecyclopropanes: A Directing Group Determined
Reaction Pathway
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Adv. Synth. Catal. 2017, 359, 1 – 11
Cheng Ji, Qin Xu, Min Shi*
Adv. Synth. Catal. 0000, 000, 0 – 0
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