Enol triflates Heck reaction

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. 

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],... 

Construction of the B ring of the congested taxol molecule 101 has been carried out by the intramolecular Heck reaction of the enol triflate 100 [46],... 

By converting the enol triflate 41 to the spiro-tricyclic dienone 42, Overman and co-workers had already shown in 1989 that the direct enantio-selective formation of quaternary chiral carbon centers ean be carried out through an intramolecular Heck reaction. While the enantioselectiv-ities were only moderate at the beginning [ 16], the same authors later succeeded in achieving the Pd(0)-BINAP-catalyzed cyclizalion of substrates of type 43 to spiro-oxindoles 44 with up to 95 % ee (Scheme 12) [17]. 

Aryl and vinyl sulfonate esters are reactive toward oxidative addition, and the perfluoroaUcyl versions are useful substrates in the Heck reaction. Conditions can be mild, comparable to those for vinyl iodide reactions. The enol (vinyl) triflates are particularly attractive, since they are prepared directly from the corresponding ketone (equation 21). ... 

Cyclizations. A great number of substrates designed for cyclization have been studied, including those leading to l-sulfinylmethylene-2-methylenecycloalkanes and to pyrroles. - Intramolecular Heck reaction involving enol triflate and allylsilane moieties is useful for the synthesis of cyclic compounds. ... 

Heck reaction) was developed 115). The cyclization substrate, acrylamide 347, was best prepared by conversion to the enol triflate 346 followed by carbonylation in the presence of 2-bromoaniline. After A-methylation of 347, the bromide was exposed to Heck conditions to provide the stereoiso-meric pentacyclic products 348 and 349 (1.5-2.0 1) in 81% yield. That the major isomer 348 has the desired configuration at the spiro center was established by H-NMR NOE experiments (Scheme 43). 

In 2010, Weinreb and coworkers reported their synthesis of communesin F (17) [30]. The synthesis began with known enol triflate 37. A Suzuki-Miyaura crosscoupling with 0-nitrophenyl boronic acid (38) followed by a two-step reaction with iodoaniline 39, afforded amide 40. A one-pot displacement of the benzyl group with ethyl carbamate, amide nitrogen protection, and a subsequent intramolecular Heck reaction provided enamide 41 (Scheme 5). 

Enol triflates are also excellent substrates in the Heck reaction. They may be prepared by the reaction of enolizable ketones with trifluoromethanesulphonic anhydride or the crystalline A, A -bis(trifluoromethanesulphonyl)anilide (A/ -phenyltriflide) [46]. The enol triflates derived from 2,2,6-trimethylcyclohexanone (90), from the r-butyldi methyl si lyl ether of 3-hydroxy-2,2,6-trimethylcyclohexanone (91), and from 2,2,5-trimethylcyclopentanone (92) couple in excellent yields (88-93%) to methyl vinyl ketone (10) in the presence of bis(triphenyl-phosphine)palladium(n) dichloride [PdCl2(PPh2)2l, to give p-ionone (2) [47], the 3-hydroxy-P-ionone derivative 93 [48], and the 5-membered-ring P-ionone analogue 94 [49], respectively (Scheme 22). 

Heck-type reactions with enol carboxylates (e.g., vinyl acetate) are generally complex. Most common are reactions in which vinyl acetate is employed as an ethylene equivalent (see Scheme 24). However, an example of a preparatively useful reaction with an intact acetate function is given in entry 44.The reaction of vinyl triflates with vinyl phosphonates affords the corresponding conjugate dienylphosphonates (entry 45).f A new access to reactive nonaflates via a one-pot nonaflation-Heck reaction was recently reported (entry 46). " This reaction sequence starts from silyl enol ethers and provides functionalized 1,3-dienes in a simple manner, lodonium salts can be used as RPd precursors (entry 47). It is notable that the palladium(O) insertion preferentially occurs inbetween the iodonium ion and the vinylic, rather than the arylic sp -hybridized carbon (entry 47). Some years ago, Jeffery used acetylenic halides to achieve (JiJ-enynoates and (Ji)-enynones in fair yields at room temperature (entry 48). ... 

Presumably the reaction occurs via the cationic manifold of the Mizoroki-Heck reaction and a bidentate phosphine is employed. Subsffate alkene geometry is critical to the stereochemical outcome and enantioselectivity of the reaction. The (Z)-alkenyl triflate 77 cyclizes to the enantiomeric enol ether 78 in high yield and greater enantioselectivity. The reaction can be utilized to perform a kinetic resolution, although reports are rare. Shibasaki... 

Since the discovery of Pd-catalyzed carbonylation of aryl, vinyl, and benzyl halides by Heck in 1974, this reaction has been used for the synthesis of ester, amide, acid, and acid anhydride. We can nse enol triflate, aryl Iriflate, aniUne derivatives, and vinyl silane as the pseudo aryl or vinyl halide. This reaction has now been further extended for the synthesis of aldehyde and ketone by combination with transmetalation. These reactions have widely been used in organic syntheses, especially the syntheses of biologically active substances in the field of fine chemistry and the syntheses of natural products. 

Treatment of a benzyl-substituted and symmetrical bis-enol tri-flate with various aryl boronic acids in the presence of Pd(OAc)2 results in a Suzuki-Miyaura cross-coupling reaction, then an intramolecular Heck reaction between the remaining triflate residue and the benzyl group and so as to give the illustrated product (eq 96).i i... 

In subsequent studies, the scope of the Heck reaction/ anion-trapping cascade was further extended using soft car-banionic nucleophiles as illustrated in the asymmetric synthesis of (—)-D -capnellene 17. Treatment of prochiral vinyl triflate 15 with Pd(OAc>2, (5)-BINAP, and NaBr, as weU as the sodium enolate of diethyl (2-((rert-butyldiphe-nylsilyl)oxy)ethyl)malonate, gave the cyclic product 16 in 87% ee and 77% yield as the sole product. The use of NaBr as an additive improved the optical yields and was critical in preventing counteranion exchange between the triflate anion and the enolate anion by complexing with sodium enolate (Scheme 13.6). Compound 16 was then advanced through several steps to complete the total synthesis (—)-D -capnellene 17. 

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