The Stille Cross-Coupling Reaction

Copyright 2005 WILEY-VCH Verlag GmbH Co. KGaA, Weinheim ISBN 3-527-31131-9 

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Despite being activated by the nitrogen atom, 2-chloroquinoline (25) is still a poor substrate for the Stille cross-coupling reactions, though yields are usually improved under Negishi conditions. For instance, the coupling of... 

Chamoin, S. Houldsworth, S. Snieckus, V. The Stille Cross Coupling Reactions on Solid Support. Link to Solution Phase Directed ortho Metala-tion. An Ester Linker Approach to Styryl, Biaryl and Heterobiaryl Carboxylic Acids, Tetrahedron Lett. 1998, 39, 4175-4178. 

The Stille cross-coupling reactions of thienyl-3-carbamate 115 with o-formyl (trimethylstannyl)pyridines 118-120 (1994JHC1161) or acetal 121 (1992MI3, 1994JHC1161, 1994JOMC127) afford a series of isomeric thienonaphthyridines 122-125. The addition of CuO to the reaction mixture leads to an increase in rate (1993JOMC127). 

Pyridine ring construction according to strategy P is based on the one-step formation of the C(4)-N(5) and C(7)-C(7a) bonds. For example, this approach provides the basis for the synthesis of the simplest isomeric dithienopyridines (1988CS281). The Stille cross-coupling reaction of 2-tributylstannyl-3-thiophene-carbaldehyde (256) with thienylcarbamates 115, 257, and 258 affords the target compounds 259-261, respectively, in different yields. 

Stille coupling between suitable 6-chloropurines and aryl(tributyl)tin afforded 6-arylpurines with a variety of substituents in the 9-position which were screened for antimycobacterial activity <02JMCI383>. The Stille cross-coupling reactions of 1,4- and l,3-bis(trialkylstannyl)benzenes with 9-benzyl-6-chloropurine gave 1,4- and l,3-bis(purin-6-yl)benzenes and 4-(purin-9-yl)benzenes <02T7431>. 

The Stille cross-coupling reaction between various heteroarylstannanes and ring-brominated benzylphosphonates (107) has been used to prepare heterobiaryl phosphonates 108. A key step in the synthesis of individual optical isomers of 2-hydroxymethyl-4-[3-(diethoxyphosphinyl)propyl]-5-alkylpiperazines 109 as CPP analogues is the alkylation of protected 5-alkyl-2-hydroxymethylpiperazines with (3-bromopropyl)phosphonate (Scheme 5). Compound 110, a new member... 

It may be that the relatively weak allyl-R bond makes RE less favorable both thermodynamically and kinetically. For an excellent summary of recent mechanistic studies of the Stille cross-coupling reaction, see R Espinet and A. M. Echavarren, Angew. Chem. Int. Ed., 2004, 43, 4704. 

A direct approach for selective construction of properly substituted bis(indole) pyrazine 100, the skeleton of a marine alkaloid dragmacidin D, has been reported. The Suzuki and the Stille cross-coupling reactions are key steps involved for regioselective introduction of two indole units [6]. 

The aryltrialkylstannanes obtained by above described methods affected the Stille cross-coupling reactions whose efficacy is presented through the following examples where arylstannanes 172-176 were reacted with aryl halides 25, 177, 178 and iodobenzene giving biaryls 179-183 in respective yields [77], Scheme 25. 

On these grounds, a synthetic methodology for the preparation of oligothiophene-5, -dioxides was developed based on the Stille cross-coupling reaction of thienylstannanes with bromo-substituted thienyl-5, 5 -dioxide units in the presence of Pd(0) catalysts [13], Subsequently, copolymers of thiophene-5, S -dioxide with thiophene were prepared both electrochemically and by action of ferric chloride [14, 15]. 

Scheme 6.6 The catalytic cycle of the Stille cross-coupling reaction [11-13].

These reactions are anployed to obtain a variety of stannanes, which are then used in the Stille cross-coupling reactions (see Chapta 19). Thus, the sequence S l-Stille reactions can be successfully applied to build complex molecules [45,46].This approach was used for the synthesis of 6-substituted uracils from 51. By performing a one-pot three-step reaction S j l-Stille-hydrolysis, it was possible to obtain 6-aryl- and 6-acyl-substituted uracils 52 in good yields (Eq. 10.18) [47] ... 

Scheme 1.6 (a) General conditions for the Stille cross-coupling reaction, (b) The proposed mechanism for the Stille cross-coupling arylation procedure [12a]. 

Another approach for the synthesis of biaryls is the Stille cross-coupling reaction. For this, chlorothiophenes 148 can be coupled with tributyl(phenyl)stannanes 149 by means of a highly active phosphanyUp-ketoiminate palladium complex 150 forming the aiylated thiophenes 151 in high yields (Scheme 59, Table 37) [357]. It is noteworthy that the reaction works with unreactive, inexpensive, and readily available chlorothiophenes 148 at room temperature. 

The reaction between an organic electrophile 1 and an organostannane 2 mediated by a transition metal catalyst (originally palladium) to form a new sigma carbon carbon bond is referred to as the Stille cross-coupling reaction (equation 1). 

Coffin et al. (2009) have shown the importance of the Stille cross-coupling reaction for the generation of conjugated polymers having fused aromatic heterocycles, especially thiophenes in their backbone. 

The palladium catalyzed cross-coupling of 3a with phenylacelylene was found to lead to decomposition of the acetylene and recovery of 3a. In another model study we employed 3c in the Stille cross-coupling reaction with acid chlorides and found the reaction led to the formation of ketone, but also several additional by-products. With so many side-reactions we deemed the reaction unsuitable for polymerization studies. We did find that the iodo derivatives undergo facile palladium/copper catalyzed alkynylation and were successful in preparing copolymer 6 (Scheme 3). Copoljuner 6 was produced in high yield and purity [M = 67,000, polydispersity 3.8]. 

Nova A, Ujaque G, Maseras F, Liedos A, Espinet P (2006) A critical analysis of the cyclic and open alternatives of the transmetalation step in the Stille cross-coupling reaction. J Am Chem Soc 128 14571-14578... 

Alvarez R, Perez M, Faza ON, de Lera AR (2008) Associative transmetalation in the Stille cross-coupling reaction to form dienes Theoretical insights into the open pathway. Organometallics 27 3378-3389... 

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