Direct alkenylations

A very interesting direct alkenylation of aryiamines at the ortho-position by the reaction of magnesium alkylidene carbenoids with A-lithio aryiamines to give 162 was reported by Satoh and coworkers (equation 40) . Magnesium alkylidene carbenoid 157, derived... 

The direct alkenylation of arylamines at the ortho position has been reported in reactions of o -chloroalkenylmagnesium chloride with N-lithioarylamines.22 Use of the CuI-L-proline catalyst system in DMSO has been found to be successful in promoting reactions of aryl iodides and bromides with activated methylene compounds, such as ethyl acetoacetate and diethyl malonate.23 The same catalyst in dioxane has been used in intramolecular cyclization of ene-carbamates leading to indoles or pyrrolo[2,3-cjpyridines.24... 

The direct alkenylation of arylamines at the ortho -position with magnesium alkylidene carbenoids has been investigated using both theoretical and experimental approaches." In some cases, the reaction has proceeded in a highly stereospecific manner at the carbon bearing the chlorine and the sulflnyl group. 

Under catalysis by an Ru complex, alkynylsilanes react with pyridines to give ( )-2-alkenylated pyridines (Equation (15)).71 This regio- and stereoselective direct alkenylation has been proposed to proceed via cationic Ru vinylidene complex 9. 

In a recent work, Piguel has shown that direct alkenylation of various electron-rich heterocycles by alkenyl bromides is possible under copper catalysis [99], Employing a combination of Cul with tra n v-1,2-A, /V - dim e l It y Ic y c I o It exan e diamine ligand and fBuOLi base, 5-aryloxazoles, benzothiazole, benzoxazole, and unsubstituted oxazole were alkenylated by P-bromostyrenes and isocrotyl bromide in good... 

Direct alkenylation of benzene derivatives with alkenes was reported by Fujiwara in 1967 and via mercuration by Heck in 1968 using a stoichiometric amount of Pd(II) salts [2], Then, inspired by the discovery of oxidative addition of iodoben-zene to Pd(PPh3)4 to generate Ph-Pd-I by Fitton in 1968 [3], Mizoroki and Heck independently reported the alkenylation of benzene derivatives by the reaction of... 

Scheme 5.58 Rh-catalyzed asymmetric direct alkenylation of biaryl derivatives with olefins reported by You.

The direct alkenylation of aromatics tolerates a variety of alkenes. Besides the alkenes mentioned above, lower alkenes (e.g. 1-butene, propene) [6], alkenes containing polar groups (e.g. acrylonitrile) [4b] and cychc alkenes such as cyclooctene [7] all participate in the palladium(II)-promoted substitution of arenes. In most cases, however, the yields of these reactions were prohibitively low (less than 20%). 

Importantly, one can effect a chemoselective direct alkenylation of aromatic halides without reacting with the carbon-halogen bond [11]. Murakami and coworkers [12] reported a chemoselective C-3 alkenylation of 4-bromo-l-tosylindole (17) with methyl 2-ferf-butoxycarbamoylacrylate (18) in the presence of stoichiometric Pd(OAc)2 and 1 equiv chloranil. The reaction smoothly generated 4-bromodehydrotryptophan derivative... 

Besides Pd, Rh and Ru catalysts have also been employed for the Fujiwara-Moritani reaction [10]. Such catalyst systems have been foimd to be applicable for chelate-directed alkenylation reactions (see later discussion). 

Through the carboxyl-directed alkenylation/decarboxylation procedure, a series of meta-substituted stilbenes can be synthesized from ortho-substituted benzoic acids (Scheme 18.13). 

Yu and coworkers [25] succeeded in performing hydroxy-directed alkenylation of 2-methyl-l-(2-methylphenyl)propan-2-ol with ethyl acrylate (Scheme 18.25). 

Rh-catalyzed ortho alkenylation reactions have been develop>ed remarkably [10a]. In all cases, [Cp RhCl2]2 is employed as a catalyst precursor, as in the early example with benzoic acids as the substrates (Scheme 18.11) [12]. Glorius [28] and Li s groups [29] reported the amide-directed alkenylation of acetanilides and benzanilides, respectively (Scheme 18.28 and Scheme 18.29). 

Other carbonyl compounds, ketones [30], esters [31], and carbamates [32] also undergo carbonyl-directed alkenylation (Scheme 18.30, Scheme 18.31, and Scheme 18.32). 

A nitrogen atom in heteroarenes such as azoles and pyridine also acts as good anchor in directed alkenylation. The authors reported the alkenylations of phenylpyrazoles, -imidazole, and -pyridine [36]. Depending on the ratio of substrates employed, mono- and diaUcenylated products can be obtained selectively. Using the procedure, one-pot synthesis of unsymmetrically substituted 1,3-dialkenylbenzene derivatives was achieved (Scheme 18.36). In contrast to the cases using a Rh catalyst, monoalkenylated phenylpyrazoles are formed predominantly under ruthenium catalysis, even in the presence of excess alkenes [37]. 

Pyridine nitrogen-directed alkenylation of C(sp )-H bond under Pd catalysis was achieved by Sanford and coworkers [39] (Scheme 18.38). 

The Pd-catalyzed direct alkenylation procedure was extended to a wide range of heteroarenes. Hirota and coworkers [50] reported that uracils undergo the reaction to give C5-alkenylated products (Scheme 18.52). 

C2-Alkenylated pyridines were found to be obtained through the sequence of the Pd-catalyzed direct alkenylation of pyridine N-oxides and following deoxygenation (Scheme 18.62) [60]. 

The transition-metal-catalyzed direct alkenylation reactions of aromatic and heteroaromatic substrates accompanied by C-H bond cleavage have been developed significantly in past few decades. These reactions provide powerful tools for preparing a wide range of -conjugated molecules from simple, readily available... 

Li H, Li Y, Zhang XS, Chen K, Wang X, Shi ZJ (2011) Pyridinyl directed alkenylation with olefins via Rh(III)-catalyzed C-C bond cleavage of secondary arylmethanols. J Am Chem Soc 133 15244... 

Olefination via Pd(II) C—H functionalization is not limited to carbon-based arenes. Olefination of the C-2 position of pyridines can be accomplished through the A-oxide. Intra-molecular-directed alkenylation of pyridines leading to... 

The direct alkenylation of azoles has been shown to be possible with alkenyl halides " and was later made possible with alkenes via an oxidative Fnjiwara-Moritani reaction." In the presence of palladinm acetate as the catalyst and silver acetate as the oxidant, Miura showed that snbstituted thiazoles and oxazoles 145 could be alkenylated to afford products 146A-D in good yields (Scheme 10.50). 

Vinylthiophenes 10 can be synthesized by direct introduction of alk-l-enyl or alk-l-ynyl groups using equimolar amotmts of palladium(II) chloride or palladium (11) acetate (Scheme 6, Table 2) [28, 30, 31]. A convenient method for the preparation of mono-alkenylated thiophenes is direct alkenylation with catalytic amounts of... 

C-H alkenylation and decarboxylation (Scheme 4.48) [53], as in the reaction of benzoic acids described above (Schemes 4.28 and 4.29). Since the palladium-catalyzed Fujiwara-Moritani type direct alkenylation of indoles usually takes place at the C3-position, it enables alkenylation at a position complementary to that of the Fujiwara-Moritani reaction, being of unique synthetic utility. On the other hand, the reaction of thiophene-2-carboxylic acid leads to the formation of a mixture of C2- and C3-alkenylated products. Decarboxylation may take place too early to complete directed C-H alkenylation at the C3-position. In contrast, the exclusive C3-alkenylation on a thiophene ring is possible under rhodium catalysis (Scheme 4.49) [34b]. 

Direct Alkenylation/Alkynylation. Alkenyl bromides can be coupled to the 2-position of oxazole in moderate yields in the presence of Cul, f-BuOLi, and a diamine ligand (eq 28). The reaction presumably proceeds through the deprotonation of the reaction site followed by metalation. This method was later extended to also include alkynyl bromides. ... 

Direct Alkenylation. A C2-alkenylation of purines and heteroarenes including oxazole utilizing styryl bromide was reported. Palladium acetate and Cul function as co-catalysts ... 

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