Alkenyl halides, coupling with metals

Ma recently demonstrated that 2-haloanilides can undergo coupling with metal sulfides subsequent intramolecular condensation affords substituted benzothia-zoles (3). Thioamides and thioureas also serve as precursors to benzothiazoles (vide infra). In addition to S -arylation reactions, alkenyl halides are also effective... 

The general mechanism of coupling reactions of aryl-alkenyl halides with organometallic reagents and nucleophiles is shown in Fig. 9.4. It contains (a) oxidative addition of aryl-alkenyl halides to zero-valent transition metal catalysts such as Pd(0), (b) transmetallation of organometallic reagents to transition metal complexes, and (c) reductive elimination of coupled product with the regeneration of the zero-valent transition metal catalyst. 

Secondary bromides and tosylates react with inversion of stereochemistry, as in the classical SN2 substitution reaction.24 Alkyl iodides, however, lead to racemized product. Aryl and alkenyl halides are reactive, even though the direct displacement mechanism is not feasible. For these halides, the overall mechanism probably consists of two steps an oxidative addition to the metal, after which the oxidation state of the copper is +3, followed by combination of two of the groups from the copper. This process, which is very common for transition metal intermediates, is called reductive elimination. The [R 2Cu] species is linear and the oxidative addition takes place perpendicular to this moiety, generating a T-shaped structure. The reductive elimination occurs between adjacent R and R groups, accounting for the absence of R — R coupling product. 

Transition metal-catalyzed transformations are of major importance in synthetic organic chemistry [1], This reflects also the increasing number of domino processes starting with such a reaction. In particular, Pd-catalyzed domino transformations have seen an astounding development over the past years with the Heck reaction [2] - the Pd-catalyzed transformation of aryl halides or triflates as well as of alkenyl halides or triflates with alkenes or alkynes - being used most often. This has been combined with another Heck reaction or a cross-coupling reaction [3] such as Suzuki, Stille, and Sonogashira reactions. Moreover, several examples have been published with a Tsuji-Trost reaction [lb, 4], a carbonylation, a pericyclic or an aldol reaction as the second step. 

Hayashi et al.74 described a process of kinetic resolution in the coupling of Grignard reagents R Mgx (having a chiral center at the point of attachment to the metal) with various alkenyl halides under the influence of chiral phosphine-nickel complexes. Chiral amino acid derivatives (35) were used as ligands. 

The copper-catalysed, Ullman-type coupling of aryl, heteroaryl and alkenyl halides may be achieved at ambient temperature using copper(I) thiophene-2-carboxylate as catalyst.60 A new semiconducting poly(anthraquinone-l,5-diyl) with nitro groups at the 4- and 8-positions has been prepared by Ullman-type coupling using metallic copper or a zerovalent nickel complex as catalyst.61... 

Transition metal-catalyzed cross-coupling reactions between vinyl organometallic compounds and unactivated alkyl halides that can be usually performed with palladium, nickel and cobalt are of particular synthetic interest [37-39]. Recently, the groups of Cahiez [48] and Cossy [49] concurrently reported the first iron-catalyzed reaction of alkenyl Grignard compounds with primary and secondary alkyl halides (X=Br, I) (Scheme 5.15). The two protocols basically differ in the iron source... 

Three transmetallation reactions are known. The reaction starts by the oxidative addition of halides to transition metal complexes to form 206. (In this scheme, all ligands are omitted.) (i) The C—C bonds 208 are formed by transmetallation of 206 with 207 and reductive elimination. Mainly Pd and Ni complexes are used as efficient catalysts. Aryl aryl, aryl alkenyl, alkenyl-alkenyl bonds, and some alkenyl alkyl and aryl-alkyl bonds, are formed by the cross-coupling, (ii) Metal hydrides 209 are another partner of the transmetallation, and hydrogenolysis of halides occurs to give 210. This reaction is discussed in Section 3.8. (iii) C—M bonds 212 are formed by the reaction of dimetallic compounds 211 with 206. These reactions are summarized in Schemes 3.3-3.6. 

The insight that zinc ester enolates can be prepared prior to the addition of the electrophile has largely expanded the scope of the Reformatsky reaction.1-3 Substrates such as azomethines that quaternize in the presence of a-halo-esters do react without incident under these two-step conditions.23 The same holds true for acyl halides which readily decompose on exposure to zinc dust, but react properly with preformed zinc ester enolates in the presence of catalytic amounts of Pd(0) complexes.24 Alkylations of Reformatsky reagents are usually difficult to achieve and proceed only with the most reactive agents such as methyl iodide or benzyl halides.25 However, zinc ester enolates can be cross-coupled with aryl- and alkenyl halides or -triflates, respectively, in the presence of transition metal catalysts in a Negishi-type reaction.26 Table 14.2 compiles a few selected examples of Reformatsky reactions with electrophiles other than aldehydes or ketones.27... 

The stereodefined alkenyl halides are of prime importance due to the recent developments of di- or trisubstituted alkene synthesis by cross-coupling reactions between organometallics and alkenyl halides catalyzed by transition metal compounds 171). These alkenyl halides can be conveniently obtained from alkenylboranes or alkeneboronic acids. B-Alk enylcatecholboranes undergo rapid hydrolysis when stirred with excess water at 25 °C (Eq. 109)102). The alkeneboronic acids are usually crystalline solids of low solubility in water and can be easily isolated and handled in air without significant deterioration. 

The stereospecific insertion of 2-monosubstituted alkenyl carbenoids was successfully employed in the preparation of 1-alkyl-1-zircono-dienes. The Z and E carbenoids of 1-chloro-l-lithio-l,3-butadiene (69 and 70, respectively) are generated in situ fromE- andZ-l,4-dichloro-2-butene [53] (Scheme 25). Inversion of configuration at the carbenoid carbon during the 1,2-metalate rearrangement stereospecifically yields terminal dienyl zirconocenes 71 and 72 [54] (Scheme 25). As the carbenoid-derived double bond is formed in 9 1=Z E for 69 and >20 1=E Z isomeric mixtures for 70, the metalated dienes 71 and 72 are expected to be formed with the same isomeric ratio. Carbon-carbon bond formation was achieved by palladium-catalyzed cross-coupling with allyl or vinyl halides to give the functionalized products with >95 5 stereopurity [55-57]. 

The cross-coupling of organozinc compounds has been accomplished using a number of metal enolate complexes, namely Rh(acac)(H2C=CH2)2 (6) , Co(acac)3 (30) °, Ni(acac)2 (47) , Li(acac) (107) and Cr(acac)3 (108) . For instance, complex 47 proved to be an extremely effective catalyst system for the Negishi cross-coupling of arylzinc halides (109) with aryl (110), heteroaryl and alkenyl halides, triflates and nonaflates to give the corresponding biaryl compounds (111) (equation 30). The solvent played an important role in these reactions and optimal conditions were found with 8 1 mixtures of THF and A-ethylpyrrolidinone (nep). Only 0.05 mol% of the nickel complex... 

Oxidative addition of the carbon-halogen bond is a well-documented reaction for Group 10 transition metal complexes, but it is relatively limited for ruthenium. The example given here involves the reversible oxidative addition of allyl halide to RuCp(CO)2X to produce RuCp(p -allyl)X2 [78]. Oxidative addition of allyl halide to a Ru(0) complex Ru(l,5-COD)(l,3,5-COT) is also reported, but the product yield was poor [79]. Nevertheless, a catalytic Heck-type alkenylation of bromostyrene with methyl acrylate by Ru(l,5-COD)(l,3,5-COT) proceeded smoothly [80]. A cross-coupling reaction of alkenyl halide with Grignard reagents or alkyl lithium also pro-... 

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