Alkene From enol triflate

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. 

Coupling with enol esters (7, 93). A new synthesis of an alkyl-substituted alkene involves coupling of a lithium dialkyl cuprate with an enol triflate,1 available from a ketone by reaction with triflic anhydride and 2,6-di-t-butylpyridine.2 A wide variety of organocuprates can be used and the geometry of the enolate is largely retained. Reported yields are in the range 60 100%. 

For strychnine 3, the ketone 11 was converted to the alkene 12 by reduction of the enol triflate derived from the more stable enolate. Deprotection and acylation gave 13, which was cyclized with Pd to give, after equilibration, the diene 14. Alkylation, to give 15, followed by Pd-mediated cyclization then gave 16, which was reduced and cyclized to (-)-strychnine 3. 

HSAB is particularly useful for assessing the reactivity of ambident nucleophiles or electrophiles, and numerous examples of chemoselective reactions given throughout this book can be explained with the HSAB principle. Hard electrophiles, for example alkyl triflates, alkyl sulfates, trialkyloxonium salts, electron-poor car-benes, or the intermediate alkoxyphosphonium salts formed from alcohols during the Mitsunobu reaction, tend to alkylate ambident nucleophiles at the hardest atom. Amides, enolates, or phenolates, for example, will often be alkylated at oxygen by hard electrophiles whereas softer electrophiles, such as alkyl iodides or electron-poor alkenes, will preferentially attack amides at nitrogen and enolates at carbon. 

C(2)-C(3) fused polycyclic cephalosporins have received considerable attention as new candidates for /3-lactam antibiotics. An access to tricyclic cephalosporins based on metal-promoted alkenylation of 3-trifloxy-A3-cephem and subsequent Diels-Alder reaction has been published <1996TL5967>. Alternatively, the reaction of a cephalosporin triflate with silyl enol ethers and silylketene acetals has been described to afford tri- and tetracyclic cephalosporins <1996TL7549>. A related process is the formation of fused polycyclic cephalosporins 27 and 28 bearing a wide range of functionalities from the reaction of cephalosporin triflates 26 with unsaturated compounds (alkenes and alkynes) and a base (Scheme 5) <1997JOC4998>. These studies have suggested that the reaction proceeds via the intermediacy of a six-membered cyclic allene which undergoes concerted nZs + K2a cycloaddition with alkenes and acetylenes. 

Kobayashi et al. found that lanthanide triflates were excellent catalysts for activation of C-N double bonds —activation by other Lewis acids required more than stoichiometric amounts of the acids. Examples were aza Diels-Alder reactions, the Man-nich-type reaction of A-(a-aminoalkyl)benzotriazoles with silyl enol ethers, the 1,3-dipolar cycloaddition of nitrones to alkenes, the 1,2-cycloaddition of diazoesters to imines, and the nucleophilic addition reactions to imines [24], These reactions are efficiently catalyzed by Yb(OTf)3. The arylimines reacted with Danishefsky s diene to give the dihydropyridones (Eq. 14) [25,26], The arylimines acted as the azadienes when reacted with cyclopentadiene, vinyl ethers or vinyl thioethers, providing the tet-rahydroquinolines (Eq. 15). Silyl enol ethers derived from esters, ketones, and thio-esters reacted with N-(a-aminoalkyl)benzotriazoles to give the /5-amino carbonyl compounds (Eq. 16) [27]. The diastereoselectivity was independent of the geometry of the silyl enol ethers, and favored the anti products. Nitrones, prepared in situ from aldehydes and N-substituted hydroxylamines, added to alkenes to afford isoxazoli-dines (Eq. 17) [28]. Addition of diazoesters to imines afforded CK-aziridines as the major products (Eq. 18) [29]. In all the reactions the imines could be generated in situ and the three-component coupling reactions proceeded smoothly in one pot. 

While not receiving as much attention as vinyl phosphates, vinyl triflates have been successfully employed as intermediates in the transformation of ketones into alkenes (Scheme 31). As in the case of vinyl phosphates, regioselective alkene formation ultimately results from kinetic or thermodynamic enol-ate generation (Scheme 32). ... 

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