Stille coupling reactions scope

Carreira and co-workers have also extended the scope of aldehydes that may be utilized in catalytic addition reactions to include stannylpropenal 108 as a substrate (Table 8B2.12, Entry 7). The adduct produced from the aldol addition of 105 is isolated with 92% ee and serves as a useful building block, as it is amenable for further synthetic elaboration (Scheme 8B2.9). Thus, vinylstannane 109 is a substrate for Stille cross-coupling reactions to give a diverse family of protected acetoacetate adducts 110. Following deprotection of the masked keto ester, the corresponding hydroxy keto ester 111 may be converted to either the syn or anti skipped polyols 112 or 113. A recent total synthesis of macrolactin A by Carreira and co-workers utilizes aldol... 

Altogether, mechanistic understanding of both coupling processes, oxidative and non-oxidative, still requires much work. Improvements here may be promising for development of new coupling methods, enriching the already wide scope of acetylenic coupling reactions. 

The scope and limitations of Pd(0)-mediated coupling reactions between aromatic halides linked to a polystyrene resin and boronic acid derivatives (Suzuki coupling) or arylstannanes (Stille coupling) have been reported. For all the reactions, the conditions were optimized and evaluated with various reagents. In most cases, products were obtained in excellent yields upon cleavage from the solid support (Eq. (63)) [101]. 

The scope of the Heck and related coupling reactions was substantially broadened by the development, in the last few years, of palladium/ligand combinations which are effective with the cheap and readily available but less reactive aryl chlorides [86, 87] rather than the corresponding bromides or iodides. The process still generates one equivalent of chloride, however. Of interest in this context, therefore, is the report of a halide-free Heck reaction which employs an aromatic carboxylic anhydride as the arylating agent and requires no base or phosphine ligands [89]. 

While organic chlorides, bromides, and iodides are still the most common substrates, recently the scope has been expanded to include organic fluorides, nitriles, ethers, triflates, phosphates, iodonium salts, and substrates with various chalconide-leaving groups. Of the different cross-coupling reactions covered in this article, the Kumada Corriu protocol has been the least reviewed. However, the topic has been covered in recent historical treatments. ... 

Unlike other cross-coupling reactions, for which the scope has rapidly expanded in recent years, the range of electrophilic substrates that can be used successfully in the Sonogashira protocol is still rather limited. Vinylic substrates (iodides, bromides, chlorides, triflates, and more recently tosylates) typically yield the best results. For aromatic substrates, iodides and triflates are preferred over bromides, which in turn give far better yields than aryl chlorides. This latter aspect of the reaction is particularly frustrating when one considers the recent advances in the activation of aryl chloride substrates for reactivity in other cross-coupling protocols. ... 

Good yields are achieved for five- and six-membered ring cyclizations by the intramolecular cross-coupling reaction of haloalkenes [139, 152], but the scope of reaction is still limited by the availability of the haloalkenes, particularly because of the absence of a simple method for preparing cyclic haloalkenes from ketone precursors. The ready availability of triflates from carbonyl compounds now offers a valuable tool for the annulation of ketones (Scheme 2-56) [160]. 

Blaser and Spencer used aroyl halides in place of aryl halides, with aroyl chlorides being of specific interest as ubiquitous, relatively cheap compounds ( Blaser reaction ) [24], This latter reaction is normally conducted in aromatic solvents phosphines are not used here as catalyst ligands since they fully inhibit the reaction. In the same way, benzoic acid anhydrides can be used as the aryl source in combination with PdCl2 and catalytic amounts of NaBr [79]. In this reaction, one of the arenes is used in the coupling reaction by elimination of CO, whereas the other benzoate serves as the base. The benzoic acid thus formed can easily be recycled into the anhydride. The use of aryl and vinyl triflates according to Cacchi [25] and Stille [26] extends the scope of the Heck coupling to carbonyl compounds phenol derivatives act via triflate functionalization as synthetic equivalents of the aryl halides. The arylation of cyclic alkenes [27], electron-rich vinyl ethers [28], and allylic alcohols [29] is accessible through Heck reactions. Allylic alcohols yield C-C-saturated carbonyl compounds (aldehydes) for mechanistic reasons (y9-H elimination), as exemplified in eq. (6). 

The reactions have a very wide scope. Acyl halides serve as substrates for Stille couplings in addition to the usual aryl and alkenyl halides however, most alkyl halides cannot be used as substrates. Like Pd-catalyzed carbonylations, reactions proceed most quickly when X = I and rather slowly when X = Cl, although especially bulky phosphine ligands such as /-Bu3P allow even aryl chlorides to undergo coupling at room temperature. Again, triflates are also widely... 

In this variation of the Pd-catalyzed cross-coupling reaction, which is closely related to the Stephen-Castro reaction, copper acetylides are reacted with (hetero)aryl halides or triflates to produce (hetero)aryl alkynes [111]. The Sonogashira reaction is comparable to the Suzuki or Stille reactions in its scope and functional group tolerability. 

Scope and limitations of the Heck reaction synthesis of dienes The Heck reaction with electron-rich alkenes A synthesis of strychnine Recent developments in the Heck reaction Sp2-sp2 Cross-Coupling Reactions by Transmetallation Stille coupling... 

The very large variety of aryl-aryl coupling reactions developed in the last decades exceeds the scope of this article. An excellent review on the formation of biaryls with special attention to the synthesis of biaryl natural products was published by Bringmann et al. [93 a] in 1990, further reviews on the Stille [94,95a], Suzuki [95], and Heck [78,79] coupling reactions appeared more recently. This survey will present some selected examples of aryl-aryl coupling and condensation reactions described in recent years with special attention on... 

Verkade has performed a very thorough study on the use of bulky proazaphos-phatrane ligands for Stille couplings of aryl chlorides. The scope and mildness of the reaction conditions are quite impressive, with a wide range of aryl and heteroaryl chlorides participating with an assortment of tin reagents (Equation 2.46) [83]. 

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