Letter pubs.acs.org/OrgLett
Rhodium-Catalyzed Alkenylation of C−H Bonds in Aromatic Amides with Alkynes Kaname Shibata, Satoko Natsui, and Naoto Chatani* Department of Applied Chemistry, Faculty of Engineering, Osaka University, Suita, Osaka 565-0871, Japan S Supporting Information *
ABSTRACT: The rhodium-catalyzed alkenylation of C−H bonds of aromatic amides with alkynes is reported. A variety of functional groups, including OMe, OAc, Br, Cl, and even NO2, are applicable to this reaction to give the corresponding hydroarylation products. The presence of an 8aminoquinoline group as the directing group is crucial for the success of the reaction.
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the rhodium-catalyzed alkenylation of aromatic amides that contain a bidentate directing group with internal alkynes.16 The hydroarylation of alkynes represents a powerful method for constructing styrene derivatives in an atom-economical manner.17,18 In a preliminary study, the reaction of amide 1a and diphenylacetylene (2a) was used as a model reaction. The reaction of amide 1a (0.3 mmol) with alkyne 2a (0.45 mmol) in the presence of [Rh(OAc) (cod)]2 (0.0075 mmol) as the catalyst in toluene (1 mL) at 140 °C for 12 h gave a mixture of E- and Z-isomers of the alkenylation product 3aa in 88% isolated yield (the E/Z ratio could not be determined) along with the cyclized isoquinolinone derivative 4aa in 8% yield (Scheme 2). A variety of conditions were examined in an attempt to avoid the formation of the undesired 4aa, but these attempts were unsuccessful. However, fortunately, the desired product 3aa and the byproduct 4aa were easily separated by silica gel column chromatography. Scheme 3 shows some representative results for the reaction of 1a with various alkynes. In all cases, trace amounts of cyclized products (equivalent to 4aa) were formed. However, they were easily separated from the major product by column chromatography. When the 6-dodecyne was used as the coupling partner, the desired product 3ab was obtained in only 63% (NMR yield) along with the cyclized product 4ab (not shown) in 21% (NMR yield), and 15% (NMR yield) of the starting amide remained unreacted. After optimization of the reaction conditions,19 the addition of 1 equiv of AcOH was found to be effective for the reaction to proceed smoothly and to achieve a high degree of selectively (81%, E/Z + inseparable structural isomers = >13/1). In the case of alkynes that contain at least one alkyl group (3ab−ae), the addition of an acid was required for the reaction to proceed efficiently. The unsymmetrical 1-phenylpropyne 2f was found to participate in the reaction, although the regioselectivity was low (A/B = 1.4:1). 4,4-Dimethyl-2-pentyne was also applicable to this reaction
umerous advances in transition-metal-catalyzed C−H bond functionalizations have been made recently.1 Transition-metal-catalyzed C−C bond-forming reactions involving C−H bond activation are currently one of the most extensively studied research topics in organic synthesis. In most cases, the presence of a directing group in the substrate is required to achieve a high degree of regioselective C−H functionalization. A bidentate chelation system has recently been shown to be a powerful system for developing new types of C−H functionalizations. One such successful example was reported by Daugulis and co-workers.2 After their seminal work, a wide variety of reactions, including arylation, alkylation, amination, sulfenylation, halogenation, oxidation, and so on, has been developed in which a bidentate chelation system is used.3 Alkynes have also been found to serve as the coupling partner in C−H functionalizations involving a bidentate system (Scheme 1). In 2011, we reported on the Ni(0)-catalyzed oxidative cyclization of C−H bonds of aromatic amides that contain a 2-pyridinylmethylamine moiety as the directing group with alkynes leading to the production of isoquinolinones.4 Later, a similar type of oxidative cyclization reaction using Ru(II), Co(II), and Fe(III) complexes as catalysts were reported by Swamy,5 Daugulis,6 and Nakamura.7 The same type of reaction using aryl sulfonamides or aryl phosphinic amides instead of aromatic amides was also reported.8 In 2016, we and Huang independently developed the Ni(II)-catalyzed oxidative cyclization of C−H bonds leading to the production of naphthalene skeletons into which two molecules of alkynes are incorporated.9,10 Cu(II)-mediated and Ni(II)-catalyzed oxidative alkynylation reactions using terminal alkynes have also been reported.11 Furthermore, Cu(II)-mediated and Co(II)- and Ni(II)-catalyzed reactions in which a product containing a five-membered ring was obtained by cyclization after oxidative alkynylation were reported.12 In addition, the Rh(I)-, Ni(II)-, and Pd(II)-catalyzed alkenylation of C−H bonds with alkynes was reported in which a picolinamide or an 8-aminoquinoline group was used as the bidentate directing group.13−15 However, alkenylation reactions of C−H bonds in aromatic amides bearing an 8-aminoquinoline bidentate directing group remain undeveloped. Herein, we report on © 2017 American Chemical Society
Received: March 9, 2017 Published: April 21, 2017 2234
DOI: 10.1021/acs.orglett.7b00709 Org. Lett. 2017, 19, 2234−2237
Letter
Organic Letters Scheme 1. Reaction of Aromatic Amides with Alkynes Utilizing a Bidentate Directing Group
with excellent regioselectivity (3ae). The functionalization of C−H bonds with unsymmetrical alkynes generally gave the corresponding vinyl products in which a small substituent group is positioned on the carbon atom adjacent to an aryl ring of the substrate.20 However, the present reaction gave 3ae, in which a bulky substituent group, such as a tert-butyl group, is attached to the carbon atom adjacent to an aryl ring. When terminal alkynes, such as phenylacetylene and triisopropylsilylacetylene, were used as the coupling partners, only trace amounts of products were obtained. Scheme 4 shows the results for the reaction of various aromatic amides with 6-dodecyne.21 To our delight, various functional groups were tolerated in the reaction, with the
Scheme 2. Rh-Catalyzed Alkenylation of C−H Bonds in Aromatic Amides with Alkynes
Scheme 3. Rh-Catalyzed Reaction of the Aromatic Amide 1a with Alkynesa
Scheme 4. Rh-Catalyzed Reaction of Aromatic Amides with 6-Dodecynea,b
a
Isolated yields. The number in parentheses refers the ratio of E/(Z + inseparable structural isomers). bIn the absence of AcOH. cn.d. = not determined. dAlkyne (0.6 mmol) and [Rh(OAc) (cod)]2 (0.015 mmol) for 24 h. eThe reaction was run on a 1 mmol scale.
a
Reaction conditions: amide (0.3 mmol), alkyne (0.45 mmol), [Rh(OAc) (cod)]2 (0.0075 mmol), AcOH (0.3 mmol), toluene (1 mL), at 140 °C for 12 h. bIsolated yields. The number in parentheses is the ratio of cis and trans isomers. cAlkyne (0.6 mmol), [Rh(OAc) (cod)]2 (0.015 mmol) for 24 h. 2235
DOI: 10.1021/acs.orglett.7b00709 Org. Lett. 2017, 19, 2234−2237
Letter
Organic Letters corresponding alkenylated products being produced in moderate to high yields. Since Br survived under the reaction conditions, the product 3fb could be elaborated to give more complex compounds by using it in additional coupling reactions. Even a NO2 group was tolerated under the reaction conditions, leading to the production of 3ib. To gain insights into the reaction mechanism, deuteriumlabeling experiments were carried out (Scheme 5). When the
Scheme 6. Plausible Mechanism
Scheme 5. Deuterium-Labeling Experiments
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ASSOCIATED CONTENT
* Supporting Information S
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.7b00709. Experimental procedures and the characterization of new compounds (PDF)
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AUTHOR INFORMATION
Corresponding Author
*E-mail:
[email protected].
reaction was carried out in the absence of an alkyne, H/D exchange was detected only at the ortho-position of the aromatic amide, even when the reaction was carried out for a short time, such as 15 min (eq 1), indicating that the C−H bond cleavage step is reversible and rapid. In addition, the addition of acetic acid had little effect on the efficiency of H/D exchange. A deuterium-labeling experiment was also carried out in the presence of an alkyne (eq 2). After 1 h, the alkenylated product 8 was obtained in 16% yield, along with the recovery of 63% of the original 1a-d8. Although AcOD was used as the additive, a proton atom was incorporated at the ortho position of the recovered 1a-d8 (0.18H). Deuterium was incorporated only at the vinyl position, but the ratio was not 100%. We currently have no explanation for what caused such a lowering of the deuterium mass balance at the present stage. A plausible mechanism for the formation of the main product 3 and byproduct 4 is shown in Scheme 6. The reaction of the amide 1 with Rh(I) forms the rhodium hydride complex C, which undergoes hydrometalation with an alkyne, after which reductive elimination and protonation gives the major product 3. The carbometalation of C with an alkyne followed by reductive elimination gives the byproduct 4. An alternative route to 4 from B is also possible. The mechanism is not clear at the present stage. In summary, we report on the rhodium-catalyzed direct ortho-alkenylation of C(sp2)−H bonds in aromatic amides with internal alkynes. The presence of an 8-aminoquinoline moiety22 as the directing group is crucial for the success of the reaction. Further studies will target a more complete investigation of the reaction mechanism which leads to this new type of reaction.
ORCID
Naoto Chatani: 0000-0001-8330-7478 Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS This work was supported by JST Strategic Basic Research Programs “Advanced Catalytic Transformation Program for Carbon Utilization (ACT-C)” from the Japan Science and Technology Agency (JPMJCR12YS). K.S. expresses his special thanks for receiving a JSPS Research Fellowship for Young Scientists. We also thank the Instrumental Analysis Center, Faculty of Engineering, Osaka University, for assistance with collecting the MS and HRMS data.
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DOI: 10.1021/acs.orglett.7b00709 Org. Lett. 2017, 19, 2234−2237
