Lactonization, silyl enolates

As discussed in Chapter 9, various nucleophiles can be introduced at the ortho position of nitroarenes via the VNS process. This provides a useful strategy for the synthesis of indoles. One of the most attractive and general methods of indoles and indolinones would be the reductive cyclization of a-nitroaryl carbonyl compounds (Eq. 10.54). The VNS and related reactions afford a-nitroaryl carbonyl compounds by a simple procedure. For example, alkylation of 4-fluoronitrobenzene with a lactone silyl enol ether followed by reductive cyclization leads to tryptophols (Eq. 10.55).73... 

When the lactone silyl enol ether U is heated to 135°C, a mixture of four stereoisomers is obtained. Although the major one is that expected for a [3,3] sigmatropic rearrangement, lesser amounts of the other possible C-4a and C-5 epimers are also formed. When the reactant is heated to 100°C, partial conversion to the same mixture of stereoisomers is observed, but most of the product at this temperature is an acyclic... 

Danishefsky, S. J. Simoneau, B. Total synthesis of ML-236A and compactin by combining the lactonic (silyl) enolate rearrangement and aldehyde-diene cyclocondensation technologies./. Am. Chem. Soc. 1989, 111, 2599-2604. 

Due to the boat geometry, dihydropyran rearrangements usually require temperatures >190°C176. In common with acyclic Claisen rearrangements using the Ireland variation, considerably lower temperatures are necessary for the rearrangement of lactonic silyl enolates... 

Danishefsky and his collaborators have shown that Claisen rearrangement of lactonic silyl enolates provides an excellent route to functionalized cycloalkenes [(76) (77)]. This methodology has been applied to a total synthesis of... 

A highly successful route to stereoisomers of substituted 3-cyclohexene-l-carboxylates runs via Ireland-Claisen rearrangements of silyl enolates of oj-vinyl lactones. The rearrangement proceeds stereospeaifically through the only possible boat-like transition state, in which the connecting carbon atoms come close enough (S. Danishefsky, 1980 see also section 4.8.3, M. Nakatsuka, 1990). 

Silyl enol ethers are other ketone or aldehyde enolate equivalents and react with allyl carbonate to give allyl ketones or aldehydes 13,300. The transme-tallation of the 7r-allylpalladium methoxide, formed from allyl alkyl carbonate, with the silyl enol ether 464 forms the palladium enolate 465, which undergoes reductive elimination to afford the allyl ketone or aldehyde 466. For this reaction, neither fluoride anion nor a Lewis acid is necessary for the activation of silyl enol ethers. The reaction also proceed.s with metallic Pd supported on silica by a special method[301j. The ketene silyl acetal 467 derived from esters or lactones also reacts with allyl carbonates, affording allylated esters or lactones by using dppe as a ligand[302]... 

Silyl enol ethers and ketene acetals derived from ketones, aldehydes, esters and lactones are converted into the corresponding o/i-unsaturated derivatives on treatment with allyl carbonates in high yields in the catalytic presence of the palladium-bis(diphenylphosphino)ethane complex (32). A phosphinc-free catalyst gives higher selectivity in certain cases, such as those involving ketene acetals. Nitrile solvents, such as acetonitrile, are essential for success. 

An efficient two-step annelation of functionalized orthoesters with trimethyl-silyloxyfuran derivatives has been reported that produces bicyclo[3. .0]lactones. ° The reaction in Scheme 7 shows an example in which the initial condensation between silyl enol ether and orthoester is followed by the radical cyclization reaction under standard conditions. It is worth underlining the complete diastereocontrol in which three contiguous stereocenters are generated in one step with >95% stereoselectivity. 

The reaction of pyrazine and quinoxaline with methyl chloroformate and bis-silyl enol ethers gave fused tetrahydropyrazine lactones 88, in an extension of previous work. There was little consistency with the variation of R in the stereochemistry of the products <06T12084>. 

Silyl enol ether 139 has also been transformed into D-allose, as shown in Scheme 5. The same methods can be applied to the enantiomeric enol ether derived from camphanate 38, and this allows one to prepare L-allose and its derivatives. Oxidation of 139 with MCPBA in THF (20 °C) led to the product of epoxide acidolysis 147 (69 %) which yielded 148 on heating to 200 °C for 15 min. Addition of 1.1 equiv. of MCPBA converted 148 into lactone 149 which in the presence of MeOH and K2CO3 (20 °C), gave selectively diester 150. Reactions 147... 

We have just seen in a preceding scheme (see Section 4.2.1.5) an example of alkylation of a silylated enolate with phenylthiomethyl chloride. The Lewis acid-promoted phenylthioalkylation of O-silylated enolates of ketones, aldehydes, esters and lactones has been used by Paterson and Fleming as a convenient synthetic route to a-alkylated or alkylidenated carbonyl compounds [323-325] according to the accompanying scheme. 

Silyl enolates are useful carbon nucleophiles in the asymmetric tandem Michael addition and lactonization (Scheme 3.3). Mukaiyama recently reported that cinchona-derived ammonium phenoxides act as activators (nucleophilic catalysis), to give highly stereocontrolled products [18-20]. In a typical PTC manner, most of the... 

Diastereo- and enantio-selective cascade of Michael addition and lactonization between various silyl enolates derived from phenyl carboxylates and -unsaturated ketones were successfully carried out by using an efficient organic catalyst, a cinchoni- dine-derived chiral quaternary ammonium phenoxide. In this asymmetric domino reaction, the corresponding tnms-3,4-dihydropyran-2-oncs were obtained in high yields with almost complete diastereoselectivities and good to excellent enantioselectivities.161... 

With cyclohexene and silyl enol ethers, under these conditions, there was no cyclization the former gave a mixture of 3- and 4-bis(methoxycarbonyl)methyl-cyclohexenes, whereas the latter afforded RC0CH2CH(C02Me)2 (up to 60%) [24], Lactones were formed from PhI=C(C4F9)C02Et with catalysis by cupric triflate [25]. 

Baeyer-Villiger oxidation of menthone [2-methyl-5-(l-methylethyl)cyclohexanone]. Alternatively, one may first convert menthone into the silyl enol ether B and cleave its C=C double bond with ozone to obtain a bifunctional compound, which exhibits a trimethylsilyl ester and an a-methoxyhydroperoxide. The latter is reduced with NaBLLi to the hydroxylated silyl ester C. The hydroxycarboxylic acid is obtained therefrom by acid-catalyzed hydrolysis. It cyclizes spontaneously to give lactone D. 

Quite recently a modification of the carbene addition reaction has been published and applied to the synthesis of phoracantholide I (11/88) [70]. The silyl enol ether 11/85 prepared from ( )-8-nonanolide underwent addition of chlorocarbene to give the intermediate bicyclic adduct 11/86, which rearranged into an E/Z-mixture of a,/J-unsaturated lactones 11/87 by heating. Phoracantholide I (11/88) was formed by hydrogenation of the latter, Scheme 11/12. 

More recently, worlc has been reported showing that silyl enol ethers of ketones, esters and lactones can be efficiently converted to a-sulfonyloxy carbonyl compounds on treatment with either [hydroxy(to-syloxy)iodo]benzene or [hydroxy(mesyloxy)iodo]benzene (equation 23). This method is similar to that used by the same workers to introduce the trifluoromethylsulfonyloxy group a to ketone carbonyl groups via their silyl enol ethers.While the major interest in these developments is the further func-tion zation of the a-position of carbonyl compounds the method clearly offers a route to a. -unsatu-rated species. 

In a maimer exactly analogous to the a-hydroxylation of ketone silyl enol ethers (Sections 2.3.2.1.3.i and 2.3.2.2.3.i) the corresponding ester silyl ketene acetals may be epoxidized by poacid and subsequently cleaved with fluoride to reveal the a-hydroxy ester.Yiel are good if hexanes are employed as solvent, while competing hydrolysis hampers the process in other media. The equivalent lactone hydroxylations are, however, not possible since hydrolysis is the dominant process even in hexane. This solvent limitation may prove restrictive to the widespread use of this technique. 

Danishefsky. S., Kitahara, T., McKee, R and Schuda, P. F Reaction of silyl enol ethers and lactone enolatcs with di-methyl(meihylenc)ammonium iodide. The bis-a-methylenation of pre-veruolcpin and pre-vemomenin,7. Am. Chem. Soc.. 98,6715, 1976 see also J. Am. Chem. Soc.. 99, 6066, 1977. 

Oida, T., Tanimoto, S., Ikehira, H., and Okano, M Reaction of 0-silylated enolates of carboxylic esters and of lactones with ami-nomethylethers, Bull. Chem. Soc. Jpn., 56, 645, 1983. 

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