Subject Number :S-16-MS-0025
Support Type : Collaborative research, Technical consultation
Proposal Title (English) : Mechanistic Studies on Cross-Coupling Reactions Catalyzed by Transition Metals
Username (English) : N. Kambe1)
Affiliation (English) : 1) Osaka University, Graduate School of Engineering

1. Summary
We previously reported Rh-catalyzed cross-coupling reaction of vinylic ethers with aryl Grignard reagents via C–O bond cleavage, in which a unique anionic diarylrhodate plays important role as the key intermediate.1 In the present study, we examined reactivities of various transition metals and found that Fe also catalyzed the cross-coupling reaction of aryl vinyl ethers with aryl Grignard reagents via selective cleavage of the vinylic C–O bond. This reaction preferred vinylic ethers as the coupling partner than aryl esters, such as tosylates and triflates of phenols, which usually shows higher reactivity toward transition metal catalysts. The present Fe catalyzed reaction does not requires costly ligands and is applicable to sterically hindered ortho-substituted aryl Grignard reagents. Mechanistic studies imply the intermediacy of low valent anionic Fe species in the C–O bond cleavage process.2
2. Experimental
The reactions of vinylic ethers with aryl Grignard reagents were conducted at rt in the presence of a catalytic amount of FeCl2 using a co-solvent of THF and dimethoxyethane (DME).
3. Results and Discussion
Firstly, the reaction of phenyl styryl ether (1a) with PhMgBr (2a) was examined at rt using various transition metal salts (Scheme 1). The desired cross-coupling product 3aa was formed in 92% yield by use of 5 mol% of FeCl2 without any ligands, indicating that iron catalysts have similar catalytic activities for this transformation as the Rh catalysts reported by us previously.1 On the other hand, other

metals are less effective as the catalyst, and Cu did not show catalytic activity.
When benzofuran (4) was employed as a cyclic aryl vinyl ether, the expected phenol derivative 5 was yielded as a mixture of E/Z isomers (Eq. 1). When diphenyl ether was employed, the coupling reaction did not take place at all and Ph2O was recovered unchanged (Eq. 2). A competitive reaction using a 1:1 mixture of vinylic ether 1a and PhOTs (6a) with p-TolMgBr (2c) gave 3ac exclusively and no biaryl 7ac was obtained (Eq. 3). Another competitive reaction using a more reactive aryl triflate led to the same result.

This reaction is triggered by the reduction of FeCl2 with two equiv of Grignard reagents takes place to generate Fe(0) and/or Fe(I), which do not directly react with vinyl ethers but do react with a Grignard reagent giving rise to anionic complex of Fe as the active catalytic species for cross-coupling reaction.
4. Others
Computational studies on catalytic cross-coupling reactions were carried out by Prof. M. Ehara (IMS).
5. Publication/Presentation
(1) T. Iwasaki, Y. Miyata, R. Akimoto, Y. Fujii, H. Kuniyasu, and N. Kambe, J. Am. Chem. Soc. 2014, 136, 9260.
(2) T. Iwasaki, R. Akimoto, H. Kuniyasu, and N. Kambe, Chem. Asian J. 2016, 11, 2834.