C-H/olefin coupling

The selective intramolecular arene C-H/olefin coupling reaction (Murai reaction) represents one of the most important discoveries in catalytic C-H functionalization chemistry (Equation (94)). 

Scheme 1. The proposed reaction pathway of the ruthenium-catalyzed C-H/olefin coupling by means of the chelation-assistance.

This C-H/olefin coupling can be extended to coupling with acetylenes [6], The reaction of aromatic ketones with internal acetylenes gives the ortho alkenylated product in high yield (Scheme 2), but reaction with terminal acetylenes does not afford the coupling product. With terminal acetylenes, dimerization of acetylenes occurs as a predominant reaction. 

Scheme 3. Proposed stepwise pathway for the ruthenium-catalyzed C—H/olefin coupling.

In (C5Me5)Rh(C2H3SiMe3)2-catalyzed C-H/olefin coupling the effect of the coordination of the ketone carbonyl is different from that in the ruthenium-catalyzed reaction [10], In the rhodium-catalyzed reaction all C-H bonds on the aromatic ring are cleaved by the rhodium complex without coordination of the ketone carbonyl. Thus, C-H bond cleavage and addition of Rh-H to olefins proceed without coordination of the ketone carbonyl. After addition of the Rh-H species to the olefin, a coordinatively unsaturated Rh(aryl) (alkyl) species should be formed. Coordination of the ketone carbonyl group to the vacant site on the rhodium atom leads... 

Although there are several examples of transition metal-catalyzed addition of C-H bonds to acetylenes, there is neither experimental evidence nor theoretical consideration in respect of a reaction mechanism for C-H/acetylene coupling. This coupling reaction is believed to proceed through a pathway similar to that proposed for C-H/olefin coupling. 

The ruthenium-catalyzed addition of C-H bonds in aromatic ketones to olefins can be applied to a variety of ketones, for example acetophenones, naphthyl ketones, and heteroaromatic ketones. Representative examples are shown in the Table 1. Terminal olefins such as vinylsilanes, allylsilanes, styrenes, tert-butylethy-lene, and 1-hexene are applicable to this C-H/olefin coupling reaction. Some internal olefins, for example cyclopentene and norbornene are effective in this alkylation. The reaction of 2-acetonaphthone 1 provides the 1-alkylation product 2 selectively. Alkylations of heteroaromatic ketones such as acyl thiophenes 3, acyl furans, and acyl pyrroles proceed with high yields. In the reaction of di- and tri-substitued aromatic ketones such as 4, which have two different ortho positions, C-C bond formation occurs at the less congested ortho position. Interestingly, in the reaction of m-methoxy- and m-fluoroacetophenones C-C bond formation occurs at the congested ortho position (2 -position). 

Several related examples of transition metal-catalyzed addition of C-H bonds in ketones to olefins have been reported (Table 2) [11-14]. The alkylation of diterpenoid 6 with olefins giving 7 proceeds with the aid of Ru(H)2(CO)(PPh3)3 (A) or Ru(CO)2(PPh3)3 (B) as catalyst [11], Ruthenium complex C, Ru(H)2(H2)(CO) (PCy3)2, has catalytic activity in the reaction of benzophenone with ethylene at room temperature [12]. The alkylation of phenyl 3-pyridyl ketone 8 proceeds with A as catalyst [13], Alkylation occurs selectively at the pyridine ring. Application of this C-H/olefin coupling to polymer chemistry using ce,co-dienes such as 1,1,3,3-tetramethyl-l,3-divinyldisiloxane 11 has been reported [14]. 

C-H bonds. In this section, among the transition-metal-catalyzed C-H/olefin coupling, ruthenium-catalyzed reactions will mainly be discussed. 

Chelation-assisted C-H/olefin coupling can be applied to the atroposelective alkylation of biaryl compounds. The reaction of 2-(l-naphthyl)-3-methylpyri-dine with ethylene using [RhCl(coe)2]2 where coe is cyclooctene, and PCy3 results in the formation of an ethylation product in 92% yield (Eq. 21) [20]. In place of the PCy3 ligand, the use of (R) - (1 - [ (S) - 2- diphenylphosphino ] ferro-cenyl)ethyl methyl ether [(R),(S)-PPFOMe] leads to the atropselective alkyla-... 

The C-H/olefin coupling of aryloxazolines proceeds with unusual product selectivity. In this case, alkylation products, i.e., formally dehydrogenation products, are obtained as a major product (Eq. 22) [11]. These types of dehydrogenation compounds are believed to be formed via a carbometalation pathway. The first example of this type of alkenylation of arenes with olefins using palladium(II) complexes via C-H bond cleavage was reported in 1967 [32]. Later, several efforts were made to perform this reaction in a catalytic manner [33]. In 2001, Milstein et al. [34] reported the oxidative alkenylation of arenes with olefins using a Ru/02/C0 catalyst system (Eq. 23). Details of the reaction mechanism have not been elucidated. 

Scheme 1 Possible reaction pathways for the C-H/olefin coupling...

These reactions can be applied to an acyclic system [66]. When reactions of tran5-4,4-dimethyl-l-phenyl-l-peneten-3-one with styrene and tri-ethoxyvinylsilane are conducted using RuH2(CO)(PPh3)3 as the catalyst, the expected olefinic C-H/olefin coupling products are obtained in good yields (Eq. 39) [66]. 

Intramolecular olefinic C-H/olefin coupling with the aid of Ru(CO)3(PPh3)2, which is also effective for the reaction of aromatic ketones with olefins, yields the carbocyclic compounds in excellent yield (Eq. 42) [67]. This type of cy-clization reaction can be extended to an asymmetric version when the [RhCl(coe)2]2/PPFOMe catalyst system is employed [68]. 

The relationship between the structure and the reactivity of the ketones has been studied [4cj. When 3-acetylthiophene was used in the coupling reaction, the alkylation took place only at 2-position (Eq. 9.2). In the cases of reactions of the ketones, shown in Scheme 9.1, no coupling product was obtained. Based on these results, Murai proposed that the a,/3-conjugate enone framework is important in the C-H/ olefin coupling reaction. 

When the alkylation of 2-atylpyridines with olefins via a C-H bond cleavage was carried out with the aid of Ru(COD)(COT) (COD = 1,5-cydooctadiene COT = 1,3,5-cyclooctatriene) and the chiral phosphine (R),(S)-PPFOMe ((R),(S)-PPFOMe = (R)-T [(S)-2-(diphenylphosphino)ferrocenyl]ethyl methyl ether), the alkylation product 5 was obtained in 15% yield with 15% e.e. (Eq. 9.7) [22]. Although the chemical and optical yields are inadequate, this result suggests that the atropselective alkylation of a biaryl compound is possible by means of a chelation-assisted C-H/olefin coupling. 

In 1996, the present authors extended their C-H/olefin coupling to the C-H/ CO/olefin coupling reaction [40]. Carbonylation of imidazole derivatives takes place in the presence of Ru3(CO)12 as the catalyst. The C-C bond formation occurs at the 4-position (Eq. 26). In these reactions, the linear ketones are the major products. Various functional groups, e.g., nitrile acetal, and ether, are tolerant. 

Kakiuchi F, Murai S (2002) Catalytic C-H/Olefin coupling. Acc Chem Res 35 826-834... 

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