Letter pubs.acs.org/OrgLett

Rhodium(III)-Catalyzed C−C Coupling of Arenes with 2‑Vinyloxiranes: Synthesis of Allylic Alcohols Songjie Yu and Xingwei Li* Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China S Supporting Information *

ABSTRACT: A rhodium(III)-catalyzed C−C coupling between 2-vinyloxiranes and arenes directed by different chelating groups has been realized via a C−H activation pathway. This reaction proceeded under conditions with a low catalyst loading, and allylic alcohols were isolated as the coupling products. A series of benzoazepanes has been synthesized by following this coupling.

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might be ascribable to the lower ligating ability of epoxide oxygen. To address this issue and to take advantage of the strain-induced reactivity of epoxides, we designed 2-vinyloxiranes as the substrate. The CC bond in 2-vinyloxirane should readily undergo insertion to a Rh−C bond to give a rhodium alkyl intermediate, which may induce the epoxide opening via β-oxygen elimination. We noted that a related allylic alcohol formation via nucleophilic addition of lithium dialkylcuperate to 2-vinyloxiranes has been reported. 10 However, using this reactive organometallic reagent may pose an issue of functional group compatibility. It will be highly desirable to take advantage of the ready availability of arenes via a C−H activation pathway. We now report our findings in the coupling of arenes and 2-vinyloxiranes under mild conditions and in high catalytic activity. We initiated our investigation with the optimization studies of the coupling of N-(2-pyrimidyl)indole and 2-vinyloxirane (2a, Table 1). Using a cationic [RhCp*(MeCN)3](SbF6)2 complex (3 mol %) as a catalyst, a coupling occurred and product 3aa was isolated in 65% yield as a result of olefin insertion and epoxide opening. Product 3aa was characterized as a mixture of allylic alcohols in 1.8:1 E/Z ratio (1H NMR analysis). Introduction of PivOH further improved the isolated yield. Thus product 3aa was isolated in 94% even at room temperature,11 where DCE was identified as the optimal solvent. Using a combination of [RhCp*Cl2]2 and AgSbF6 afforded comparable results, but for operational simplicity [RhCp*(MeCN)3](SbF6)2 was retained for further studies. By following the optimized conditions, the scope and limitations of this system were next explored (Scheme 2). N(2-Pyrimidyl)indoles bearing a large variety of electrondonating (Me, OMe, OBn) and -withdrawing (Cl, Br, COOMe) groups in the benzene ring coupled smoothly with 2-vinyloxirane. Introduction of a substituent at the 3-position of the indole ring has minimal influence (3ba and 3ca), indicative of tolerance of steric effects. In this case, the products were

unctionalized allylic alcohols are well-known as biologically active small molecules and are also key building blocks in the synthesis of natural and pharmaceutical compounds.1 Therefore, the synthesis of compounds with an allylic alcohol fragment has attracted the attention of synthetic chemists. Over the past decades, transition-metal-catalyzed C−H bond activation has emerged as a powerful tool for the formation of functionally diverse and structurally complex aromatics.2 From a step- and atom-economic standpoint, synthesis via C− H bond functionalization would be a more straightforward and attractive alternative. Recently, Rh(III)-catalyzed C−H bond functionalization3 has allowed effective construction of various C−C bonds. The oxidative C−H olefination4 of arenes and alkenes has been particularly well studied. However the direct C−H insertion into olefins under redox-neutral conditions has been rarely realized.5 To achieve this insertion, two strategies with additional driving forces have been employed (Scheme 1). Scheme 1. Rhodium(III)-Catalyzed Redox-Neutral Coupling of Arenes

Glorius, Loh, and others independently applied allyl esters to coupling with arenes under Rh(III)-catalysis, leading to allylation of C−H bonds.6 In this process, the olefin insertion is coupled with subsequent β-elimination of an acetate or carbonate leaving group. This strategy has also been extended to the coupling of allenyl carbinol carbonate.7 Alternatively, olefin insertion can be streamlined with subsequent opening of a strained cyclobutane.8 We recently reported the rhodiumcatalyzed insertion of aryl C−H bonds into N-Ts aziridines, leading to the synthesis of β-branched amines (Scheme 1).9 The analogous reaction for epoxides, however, failed even after extensive screenings. We reasoned that the poor reactivity © 2014 American Chemical Society

Received: January 9, 2014 Published: February 7, 2014 1200

dx.doi.org/10.1021/ol5000764 | Org. Lett. 2014, 16, 1200−1203

Organic Letters

Letter

Table 1. Optimization Studiesa

Scheme 3. C−H Allylation of Benzene and Thiophene Ringsa,b

entry

catalyst (mol %)

solvent

yieldb

1 2c 3 4 5 6 7 8 9

− [Cp*Rh(MeCN)3](SbF6)2 (3) [Cp*Rh(MeCN)3](SbF6)2 (3) [Cp*RhCl2]2 (1.5)/AgSbF6 (6) [Cp*Rh(MeCN)3](SbF6)2 (3) [Cp*Rh(MeCN)3](SbF6)2 (3) [Cp*Rh(MeCN)3](SbF6)2 (3) [Cp*Rh(MeCN)3](SbF6)2 (3) [Cp*Rh(MeCN)3](SbF6)2 (3)

DCE DCE DCE DCE DCM acetone THF MeCN dioxane

0 65 94 92 91 15 45

Rhodium(III)-catalyzed C-C coupling of arenes with 2-vinyloxiranes: synthesis of allylic alcohols.

A rhodium(III)-catalyzed C-C coupling between 2-vinyloxiranes and arenes directed by different chelating groups has been realized via a C-H activation...
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