Enol triflates vinylation

Unfortunately, it quickly became apparent that a shortfall in this proposal was an inability to prepare the desired vinyl halide 25 in a straightforward and selective manner [19]. In contrast, we reasoned that the selective formation of an enol sulfonate, such as the enol triflate 26a, could be controlled by judicious tuning of enolization conditions starting from the corresponding ketone, and that such an enol sulfonate would possibly be a substrate for a palladium-mediated coupling (Scheme 9.17). In this way a common intermediate from the previously defined synthesis, that is, the racemic ketone rac-13 or its cyano equivalent rac-5 could be used to generate the required enamide. 

Alkenyl trifluoromethanesulphonates (enol triflates) undergo Heck coupling with alkenes efficiently (equation 123)209a 215. This reaction is a useful variation of the use of vinyl halides not only because they are easy to prepare from the corresponding carbonyl compounds, but also because yields are good, and the stereochemistry of the triflate is largely maintained. 

Boronic acids 96 and 97 couple very well with vinyl triflates 98 and 99 under typical Suzuki conditions (Pd(PPh3)4/Na2C03/LiCl/DME) to give indoles 100 and 101, respectively, in 76-92% yield [115, 116]. Enol triflates 98 and 99 were prepared in good yield (73-86%) from N-substituted 3-piperidones, wherein the direction of enolization (LDA/THF/-78 °C PhNTf2) is dictated by the tf-substituent. 

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. 

Although the coupling of aiyl halides with alkenes (commonly referred to as the Heck reaction) was first reported more than 25 years ago [ 1 ], only in the past decade has its enormous synthetic potential been realized [2], Within that time, the reaction has been extended to many substrates, including vinyl iodides and bromides and enol triflates. Moreover, the intramolecular variant has become one of the more important reactions for the formation of carbon-carbon bonds and has emerged as a premier method for the construction of quaternary carbon centers. The ability of intramolecular Heck reactions to reliably fashion carbon-carbon bonds in polyfunctional molecules has led to wide application of this reaction at the strategy level for the synthesis of complex natural products [2g],... 

Initially the Pd(0) complex oxidatively adds to enol triflate 6 to form a vinyl-Pd(II) species. Carbon monoxide then inserts into the new Pd—C o-bond to yield a palladium(ll)-acyl complex which captures methanol. The methanolysis step is formally a reductive elimination reaction in which the Pd(0) catalyst is regenerated to propagate the catalytic cycle (Scheme 6.8).7... 

The method of Hayashi and Ozawa is neither restricted to aryl triflates nor to 2,3-dihydrofu-ranes. Vinyl triflates can also be employed, and V-(methoxycarbonyl)-pyrroline 19 as the olefin component gives even better results. Thus, the reaction of 19 with the enol triflate 20 results in the formation of 21 with excellent yield and almost complete enantioselectivity (Scheme 7) [9e]. 

Andersson, C.-M., and Hallberg, A. 1989. Palladium-catalyzed vinylation of alkyl vinyl ethers with enol triflates. A convenient synthesis of 2-alkoxy 1,3-dienes. J Org Chem 54, 1502-1505. 

These ease of preparation of vinyl and aryl triflates and the availability of the starting materials have expanded their use as a coupling partner with a terminal acetylene. Facile Pd-Cu coupling of vinyl triflates with terminal acetylenes was reported by Cacchi [51]. The cross-coupling of enol triflate 88 with phenylacetylene proceeds easily under normal conditions [Eq. (33)] [52]. For the double cross-coupling of aromatic 1,2-ditriflates with TMSA, the addition of Bu4NI accelerates enediyne formation [Eq. (34)] [53]. 

X = OTf) may fail to accomplish metal exchange and consequently hinder the formation of the alke-nylchromium reagent. Few examples of the use of enol triflates as progenitors of vinyl carbanion equivalents have appeared. Consequently, the work from Takai and coworkers is particularly useful. The alkenylchromiums generated from enol triflates are functionally indistinguishable from those generated from iodoalkenes (equation 65 and table 10). This fact is disclosed by comparison of Table 9 with Table 10. 

Ceccarelli, S., Piarulli, U., Gennari, C. Effect of ligands and additives on the palladium-promoted carbonylative coupling of vinyl stannanes and electron-poor enol triflates. J. Org. Chem. 2000, 65, 6254-6256. 

Stannylcuprates will also react with enol triflates (equation 8-21)41 and with vinyl iodides (equation 8-22)42 to give vinylstannanes, in a reaction which may be regarded either as a nucleophilic substitution or as stannylcupration followed by elimination of CuX. 

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]. 

If the electrophile is a vinyl triflate, it is essential to add LiCl to the reaction so that the chloride may displace triflate from the palladium o-complex. Transmetallation takes place with chloride on palladium but not with triflate. This famous example illustrates the similar regioselectivity of enol triflate formation from ketones to that of silyl enol ether formation discussed in chapter 3. Kinetic conditions give the less 198 and thermodynamic conditions the more highly substituted 195 triflate. 

---