Enol triflates oxidative addition

Achiral ketones, for example, 3-pentanone, can be converted predominantly into (Z)-boron enolates [(Z)/( )>97 3] by treatment with (- )-diisopinocampheylboron triflate. Subsequent addition to aldehydes, followed by an oxidative workup procedure, delivers /i-hydroxy ketones with a diastcrcomeric ratio of 95 5 to 98 2 (synjanli) and the xpn-products with 66 to 93% ee33. 

In addition to halides, some pseudohalides undergo facile oxidative addition to Pd and Ni complexes. Trifluoromethanesulfonates (triflates), namely aiyl triflates 3 derived from phenols and enol triflates of carbonyl compounds, are most useful. 

Alkenyl halides and their pseudohalides also react with Pd(0) to form the alkenylpalladium intermediates 11, and their transformations are summarized in Scheme 3.4. In addition to alkenyl halides, the enol triflates 12 undergo oxidative addition, showing that carbonyl compounds are useful starting compounds for Pd-catalysed reactions. 

Three new chirality centers are formed with high enantio- and complete diastereoselectivity in the course of the reaction of the enol triflate 37 to the bicyclo [3.3.0]octane derivative 38 (Scheme 11) [15]. In this transformation, the intermediate 39, formed by oxidative addition, leads to the cationic palladium-7r-allyl complex 40, which is finally converted to the isolated product 38 by regio- and diastereoselective nucleophilic addition of an acetate anion. The bicyclic product 38 is of interest as a building block for the synthesis of capnellene sesquiterpenes. 

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). ... 

In order to craft the lactone ring, 38 was oxidized to 40 under Swem conditions in a prelude to intramolecular 1,4-addition of the hemiacetal anion [20] formed via nucleophilic attack by methoxide ion at the aldehyde site. With the availability of acetal 41, it became necessary to consider carefully whether to elaborate the epoxy lactone segment in advance of, or subsequent to, introduction of the a,p-unsaturated ester subunit. Since the latter option was considered more workable, 41 was transformed into the enol triflate and subjected to palladium(II) catalyzed methoxycarbonylation [21]. This methodology allowed for proper homologation of 42 to 43, and subsequent conversion to 44, in totally regiocontrolled fashion. 

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. 

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),... 

Carbon-centered nucleophiles can also be used to advantage in the reaction with epoxides. For example, the lithium enolate of cyclohexanone 96 engages in nucleophilic attack of cyclohexene oxide 90 in the presence of boron trifluoride etherate to give the ketol 97 in 76% yield with predominant syn stereochemistry about the newly formed carbon-carbon bond <03JOC3049>. In addition, a novel trimethylaluminum / trialkylsilyl triflate system has been reported for the one-pot alkylation and silylation of epoxides, as exemplified by the conversion of alkenyl epoxide 98 to the homologous silyl ether 99. The methyl group is delivered via backside attack on the less substituted terminus of the epoxide <03OL3265>. 

As shown in Scheme 38, several primary alkyl-substituted cyclohexanones have been prepared by Lewis acid catalyzed phenylthioalkylation of the TMS enol ether of cyclohexanone followed by reductive removal of a phenylsulfenyl group. The two-step neopentylation sequence is particularly noteworthy. This methodology has been used to prepare numerous a-alkylated cyclic and acyclic ketones. a-Alkylated aldehydes can be produced in a like manner. a-Alkylidenation can also be accomplished by oxidative removal of sulfur. Lee and coworkers have found that TMS triflate-catalyzed reactions of silyl enol ethers of cyclic ketones and aldehydes with saturated and unsaturated l,l-dimethoxy-(i>-tri-methylstannanes, followed by addition of titanium tetrachloride, provide novel routes to fused and spiro-cyclic ring systems. Phenylthiomethylstannylations of silyl enol ethers have also been reported. ... 

The use of Montmorillonite clay, a very efllcient acidic catalyst, allows a-alkylation of / -substituted indoles ytterbium triflate can also be used to catalyse such alkylations. This efficient catalysis contrasts with the different, but very instructive, reaction pathway followed when mesityl oxide and 1,3-dimethylindole are combined in the presence of sulfuric acid - electrophilic attack at the already substituted /3-position is followed by intramolecular nucleophilic addition of the enol of the side-chain ketone to C-2. ... 

---