Enol triflates cyclization

The intramolecular coupling of organostannanes is applied to macrolide synthesis. In the zearalenone synthesis, no cyclization was observed between arylstannane and alkenyl iodide. However, intramolecular coupling take.s place between the alkenylstannane and aryl iodide in 706. A similar cyclization is possible by the reaction of the alkenylstannane 707 with enol triflate[579]. The coupling was applied to the preparation of the bicyclic 1,3-diene system 708[580]. 

Clavepictines A and B were prepared using a variety of effective reactions on the piperidine ring, such as a silver-promoted cyclization of an aminoallene intermediate, diastereoselective alkylation, and cross coupling of an enol triflate <99JA10012>. 

Triflic anhydride has been shown to activate enones (113) with an electron-rich aromatic pendant to undergo a Friedel-Crafts-like cyclization, affording the cyclic enol triflate (114).170... 

A new and related carboannulation reaction is possible, that involves insertion of alkynes to aryl or alkenyl palladium intermediates, and subsequent cyclization onto an aromatic ring already present in the substrate [252], The cyclization of the enol triflate 509 to give 510 is an example. The reaction was applied to the synthesis of the indolocarbazole derivative 512 from the iodobisindole 511 [253],... 

A synthetic method for the prepararation of cyclobutanones via an intramolecular cyclization of a ketone enolate has been reported.83 Enol triflates having a silyloxy group at the ft-position under the influence of TBAF give a cyclobutanone or a four-membered enol ether through rearrangement of the trifluoromethanesulfonyl group followed by an intramolecular C- or O-alkylation reaction (Scheme 49). 

The Nazarov cyclization has been featured in a variety of synthetic endeavors involving both natural and unnatural products. In the area of polyquinane natural products ( )-hirsutene (88), ( )-mod-hephene (89), ( )-silphinene (90), ( )-A 2)-capnellene (91) and ( )-cedrene, have all been prepared (Scheme 37). The synthesis of (91) is noteworthy in the iterative use of the silicon-directed Nazarov cyclization. TIk divinyl ketones were constructed by the carbonylation-coupling of enol triflates (92) and (95) with the -silylvinylstannane (Scheme 38). llie diquinane (94), obtained from Nazarov cyclization of (93), was transformed into enol triflate (95) which was coupled with the -silylvinylstaimane as before. Silicon-directed Nazarov cyclization of (96) was highly diastereoselective to provide the cis,anti,cis isomer of (16). The synthesis was completed by routine manipulations. 

The only asymmetric synthesis of the Nuphar indolizidine to date is due to Barluenga and co-workers (615). Their route to the (5S,8 ,8aS)-( -) enantiomer of 944 commenced with cycloaddition between the proline-derived 2-amino-butadiene 957 and imine 958 (Scheme 125). Hydrolysis of the adduct 959 gave piperidinone 960 in 51% yield and an ee of better than 99%. Once the alcohol and amine groups had been mutually protected as the cyclic carbamate 961, defimctionalization of the ketone was accomplished via an enol triflate. Chain-extension of the deprotected piperidine 962 at the hydroxymethyl substituent afforded 963, which was cyclized to the bicyclic lactam 964 simply by heating in toluene. Reduction with lithium aluminum hydride completed the synthesis of ( - )-944 ([a]n -99°, c 1.3, CH2CI2). 

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. ... 

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. 

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). 

Intramolecular cyclization processes of suitable enol triflates and iodoalkenes bearing proximate oxygen or nitrogen nucleophiles 39 via palladium-catalyzed carbonylative... 

As reported in the scheme, a careful choice of the reaction medium and temperature allowed the tandem process, giving rise to the desired compound 29 in 46% yield starting from 27. Lowering of the reaction temperature to 60 °C and performing the reaction in THF instead of PhCN results in the isolation of the sole carbonylative cyclization product 28 in 19% yield, plus 11% recovered enol triflate 27 (Scheme 13.13, path b). 

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),... 

The installation of the pharmacologically important isoquinoline group was achieved by a Stille coupling. Reduction by diimide yielded the trans-fused perhydroindane subunit in 329. An oxidation, enol triflation and reduction sequence converted 329 to enone 331. Enol triflation and deprotection afforded 332. Palladium-catalyzed vinylation, followed by a Parikh-Doering oxidation gave 333. The final and rather splendid step consisted of dimethyl imine-formation and vinysilane cyclization to furnish cortistatin J in high yield and with the correct dimethylamine stereochemistry (Scheme 18.66). 

Chiral 2-oxazolidones are useful recyclable auxiliaries for carboxylic acids in highly enantioselective aldol type reactions via the boron enolates derived from N-propionyl-2-oxazolidones (D.A. Evans, 1981). Two reagents exhibiting opposite enantioselectivity ate prepared from (S)-valinol and from (lS,2R)-norephedrine by cyclization with COClj or diethyl carbonate and subsequent lithiation and acylation with propionyl chloride at — 78°C. En-olization with dibutylboryl triflate forms the (Z)-enolates (>99% Z) which react with aldehydes at low temperature. The pure (2S,3R) and (2R,3S) acids or methyl esters are isolated in a 70% yield after mild solvolysis. 

Scheme 2.25 shows some examples of additions of enolate equivalents. A range of Lewis acid catalysts has been used in addition to TiCl4 and SnCl4. Entry 1 shows uses of a lanthanide catalyst. Entry 2 employs LiC104 as the catalyst. The reaction in Entry 3 includes a chiral auxiliary that controls the stereoselectivity the chiral auxiliary is released by a cyclization using (V-methylhydroxylamine. Entries 4 and 5 use the triphenylmethyl cation as a catalyst and Entries 6 and 7 use trimethylsilyl triflate and an enantioselective catalyst, respectively. 

Aside from alcohols, other oxygen nucleophiles have also participated in hydroalkoxylation reactions with alkynes. The most common of these are 1,3-dicarbonyl compounds, whose enol oxygens are readily available to add to alkynes. Cyclization reactions of this type have been carried out under Pd(0) catalysis with various aryl or vinyl iodides or triflates, often in the presence of CO, affording the corresponding furan derivatives (Equation (95)).337-340 A similar approach employing cyclic 1,3-diketones has also been reported to prepare THFs and dihydropyrans under Pd, Pt, or W catalysis.341 Simple l-alkyn-5-ones have also been isomerized to furans under the influence of Hg(OTf)2.342... 

---