Enol triflates Stille reaction

Enol triflates have emerged as attraetive alternatives to vinyl halides in the Stille coupling partner due to their ease of preparation from readily available carbonyl compounds. The addition of LiCI has been found to be beneficial to Stille enol triflate coupling reactions. Thus, it was not surprising that coupling 5-tributylstannylpyrimidine to enol triflate 134 proceeded in good yield in the presence of LiCI. In this case, the addition of Cul as cocatalysts was found to also be beneficial to the reaction outcome [57]. 

An application of Stille couplings to the solid phase using a traceless A-glycerol linker with 2-stannylindoles has been developed [177]. Only a few examples of the use of 3-stannylindoles in Stille reactions have been described. Ortar and co-workers prepared 169 and 170 and effected Pd-catalyzed cross coupling reactions with several aryl, heteroaryl, and vinyl substrates (bromides, iodides, triflates) to give the expected products 171 in high yields [178]. Enol triflates behave exceptionally well under the Ortar conditions, e.g., 172 to 173. 

The introduction of the allylic silane moiety required for the intermolec-ular Hosomi-Sakurai reaction is depicted in Scheme 16. Following the formation of the enol triflate 97, a Stille coupling provided excess to the allylic alcohol 98 [51]. The allylic alcohol (98) was endowed with a phosphate leaving group for the subsequent allylic substitution. Utilizing a trimethylsilyl cuprate as nucleophile for the 5 2 reaction, the allylic phosphate was converted into the allylic silane 89. A useful substrate-induced diastereoselectivity in favour of (14i )-89 was encountered at small scale but decreased significantly upon up-scaling. 

Vinyl Inflates are especially attractive in Stille reactions since they can be prepared regioselectively from enolizable ketones by trapping the enolate oxygen with triflating agents (e.g., Tf20, PhNTf2 ). For reactions of vinyl triflates with... 

In the total synthesis of the marine terpenoid (-)-frondosin B, Trauner and Hughes described an intramolecular palladium-catalyzed alkenylation reaction between a benzofuran and an enol triflate (124 to 125, Scheme 10.41). Although the mechanism to form the key seven-membered ring is still unclear, a reasonable hypothesis would involve oxidative addition of palladium(0) to the C—OTf bond, C3-palladation of the benzofuran and reductive elimination to form the new C—C bond. This work is notable as it was the first example of heteroaromatic C—H activation in a complex molecule setting. 

Process research efforts relative to the design of a practical synthesis of a structurally complex MRSA carbapenem (1) culminated in the establishment of two distinct synAeses. The first is based on a unique Stille coupling between a carbapenem enol triflate and a stannatrane appended via a methylene spacer to a complex and extended heteroaromatic side chain. The second is founded upon a novel n-allyl palladium reaction to incorporate die entire complex side chain. Details on die development of both methods are described. 

In 2002, Trauner and coworkers reported the total synthesis of (—)-frondosin B (Scheme 16.19) [39]. In their synthesis, a palladium-catalyzed C-H alkenylation of benzofuran with an enol triflate was used for the construction of the seven-membered ring in frondosin B. Treatment of triflate 95 with catalytic Pd(PPh3) and f-PrjNEt in Af,Af-dimethylacetamide (DMAc) afforded cyclized product 97 in 70% yield. Although the mechanism of the coupling reaction is still unclear, the catalytic cycle might involve (i) C-OTf oxidative addition of 95 to Pd(0),... 

Although in the recent years the stereochemical control of aldol condensations has reached a level of efficiency which allows enantioselective syntheses of very complex compounds containing many asymmetric centres, the situation is still far from what one would consider "ideal". In the first place, the requirement of a substituent at the a-position of the enolate in order to achieve good stereoselection is a limitation which, however, can be overcome by using temporary bulky groups (such as alkylthio ethers, for instance). On the other hand, the ( )-enolates, which are necessary for the preparation of 2,3-anti aldols, are not so easily prepared as the (Z)-enolates and furthermore, they do not show selectivities as good as in the case of the (Z)-enolates. Finally, although elements other than boron -such as zirconium [30] and titanium [31]- have been also used succesfully much work remains to be done in the area of catalysis. In this context, the work of Mukaiyama and Kobayashi [32a,b,c] on asymmetric aldol reactions of silyl enol ethers with aldehydes promoted by tributyltin fluoride and a chiral diamine coordinated to tin(II) triflate... 

Vinyl triflates (C=C-0S02CF3) react with vinyl tin derivatives in the presence of palladium catalysts to form dienes, in what is known as the Stille coupling. Vinyl triflates can be prepared from the enolate by reaction with Al-phenyl trifli-... 

The Mannich and related reactions provide one of the most fundamental and useful methods for the synthesis of y -amino ketones and esters [46]. Although the classical protocols include some severe side reactions, new modifications using preformed iminium salts and imines have improved the process. Some of these materials are, however, unstable and difficult to isolate, and deaminations of the products that occur under the reaction conditions still remain as problems. The direct synthesis of /5-amino ketones from aldehydes, amines, and silyl enolates under mild conditions is desirable from a synthetic point of view [47, 48]. Our working hypothesis is that aldehydes could react with amines in the hydrophobic micellar system in the presence of a catalytic amount of lanthanide triflate and a surfactant to produce imines, which could react with hydrophobic silyl enolates [49]. 

The demand for environmentally friendly chemistry and its widespread applicability have made water an increasingly popnlar solvent for organic transformations. Mixtures of water and other solvents snch as tetrahydrofnran are now commonly anployed for a number of organic transformations. For instance, the Lewis acid catalysed aldol reaction of silyl enol ethers, commonly known as the Mnkaiyama aldol reaction, which was firstly reported in the early seventies, can be carried ont in snch media. With titanium tetrachloride as the catalyst this reaction proceeds regioselectively in high yields, but the reaction has to be carried ont strictly nnder non-aqneons conditions in order to prevent decomposition of the catalyst and hydrolysis of the sUyl enol ethCTS. In the absence of the catalyst it was observed that water had a beneficial influence on this process (Table 4, entry D) . Nevertheless, the yields in the nncatalysed version WCTe still unsatisfactory. Improved results were obtained with water-tolerant Lewis acids. The first reported example for Lewis acid catalysis in aqueous media is the hydroxymethylation of silyl enol ethers with commercial formaldehyde solution using lanthanide trillates. In the meantime, the influence of several lanthanide triflates in cross-aldol reactions of various aldehydes was examined " " ". The reactions were most effectively carried out in 1 9 mixtures of water and tetrahydrofnran with 5-10% Yb(OTf)3, which can be reused after completion of the reaction (Table 19, entry A). Although the realization of this reaction is quite simple, the choice of the solvent is crucial (Table 20). 

Use of diisopinocampheyl boron chloride in place of the triflate affords E(0)-enolates, but the isopinocampheyl ligands were ineffective for anti aldol reactions [48]. Encouraged by the molecular mechanics analysis of the ZfOj-enolate additions, Gennari and Paterson used computational methods to design a new boron ligand for use with E(G)-enolates [97]. The design was cued by Still s comment [98] that cis-2-... 

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