Reductive modification of difluoromethylene moiety in pentafluoropropionyl group

The reductive Mg-promoted defluorinative-silylation of 2,2,3,3,3-pentafluoropropiophenone readily produces the α-trifluoromethyl enol silyl ether, which then react with electrophiles to give a variety of 2-substituted-3,3,3-trifluoropropiophenones in excellent yields. The same protocol is applicable for the preparation of enol silyl ether of 3,3,3-trifluoropropiophenone. Fluoride ion catalyzed 1,2-desilylative-defluorination of 2,3,3,3-tetrafluoro-2-trimethylsilyloxypropiophenone provided 3,3,3-trifluoro-1-phenyl-1,2-propanedione in a good yield.     

New approaches toward the synthesis of (D-homo) steroid skeletons using Mukaiyama reactions

New, short, and flexible procedures have been developed for syntheses of steroid and D-homo steroid skeletons. A Mukaiyama reaction between the silyl enol ether of 6-methoxytetralone and 2-methyl-2-cyclopentenone or carvone, with transfer of the silyl group to the receiving enone, gave a second silyl enol ether. Addition of a carbocation, generated under Lewis acid conditions from 3-methoxy-2-butenol, 3-ethoxy-3-phenyl-2-propenol or 3-methoxy-2-propenol to this second silyl enol ether gave adducts, which could not be cyclized by aldol condensation to (D-homo) steroid skeletons. The Mukaiyama-Michael reaction of the silyl enol ether of 6-methoxy tetralone with 2-methyl-2-cylopentenone gave a second silyl enol ether, which reacted in high yield with a carbocation generated from 3-hydroxy-3-(4-methoxyphenyl)propene. Ozonolysis of the double bond in this adduct gave a tricarbonyl compound (Zieglers triketone), which has been used before in the synthesis of 9,11-dehydroestrone methyl ether. A second synthesis of C17 substituted CD-trans coupled (D-homo) steroid skeletons has been developed via addition of a carbocation, generated with ZnBr₂ from a Torgov reagent, to a silyl enol ether containing ring D precursor. The obtained seco steroids have been cyclized under formation of the 8-14 bond by treatment with acid. The double bonds in one of the cyclized products have been reduced to a C17-substituted all trans steroid skeleton.     

Reactions of novel mono- and difluoroacetyltrialkylsilanes with sulfur and phosphorus ylides

The reactions of difluoroacetyltrialkylsilanes with methylidene triphenylphosphorane and benzylidene triphenylphosphorane are affected by the nature of the silyl substituents giving either the enol silyl ether or normal Wittig product exclusively, or mixture of both. Reactions with Horner-Emmons type ylide gave only the alkene products. Reactions of mono- and difluoroacetyltrialkylsilanes with dimethylsulfoxonium methylide gave the enol silyl ether products exclusively. Conversion of an enol silyl ether to an epoxide was effected with m-CPBA.     

Synthesis of the hydroazulene portion of guanacastepene A using a [2.3]sigmatropic sulfoxide rearrangement: observations on silyl enol ether electrophilic chemistry for the introduction of the C-13 hydroxyl group

The intermediate 6 can be converted into enone 13 using a [2.3]sigmatropic sulfoxide rearrangement as the key transformation. The C-13 hydroxylation of 13 was studied, and found to give 14 (epimeric to guanacastepene A). Examination of silyl enol ethers of 13 demonstrated the ready isomerization of the kinetic silyl enol ether into the more stable thermodynamic silyl enol ether under mild electrophilic reaction conditions.     

Crucial role of the ligand of silyl Lewis acid in the Mukaiyama aldol reaction

The Me3SiX-induced Mukaiyama aldol reaction proceeds through each catalytic cycle under the influence of X-: the silyl group of Me3SiNTf2 does not release from -NTf2 and that of silyl enol ether intermolecularly transfers to the product, while the silyl group of Me3SiOTf remains in the product and that of the silyl enol ether becomes the catalyst for the next catalytic cycle.     

Oxidative C-C bond-forming reaction of electron-rich alkylbenzyl ether with trimethylvinyloxysilane

Treatment of an electron-rich benzyl ether with DDQ at ambient temperature followed by addition of a silyl enol ether undergoes a C-C bond-forming reaction to afford 3-alkoxy-3-phenyl-propionyl compound. This is a general reaction and works well with a variety of silyl enol ethers to give carbonyl products in yields ranging from 10 to 85%.     

Synthesis of 14-Bromo and 14-Hydroxy Baccatin III Derviatives

Numerous efforts towards synthesis of anticancer drug paclitaxel (Taxol(r), 1a) with improved activities led to the modification at 13-phenylisoserine side chain and different positions of its core structure-baccatin III 1c1. At the same time, the activities of searching new taxoids for starting materials of new semi-synthetic paclitaxel analogs from Taxus spp. plant have not ever been stopped. Among these taxoids, 14?-hydroxy-10-deacetylbaccatin III 22 and 13-acetyl-9-dihydrobaccatin III …     

Synthesis of medium-sized cyclic γ-haloketones by radical mediated ring-opening reaction of Lewis acid catalyzed (2+2)-cycloaddition products

Novel entry to synthesize medium-sized cycloalkanones is described. Thus, employment of catalytic (2+2)-cycloaddition for cyclic silyl enol ether followed by radical mediated ring-opening reaction provided medium-sized γ-halocycloalkanones.     

alpha-Nitration of Ketones via Enol Silyl Ethers. Radical Cations as Reactive Intermediates in Thermal and Photochemical Processes

Highly colored (red) solutions of various enol silyl ethers and tetranitromethane (TNM) are readily bleached to afford good yields of alpha-nitro ketones in the dark at room temperature or below. Spectral analysis show the red colors to be associated with the intermolecular 1:1 electron donor-acceptor (EDA) complexes between the enol silyl ether and TNM. The formation of similar vividly colored EDA complexes with other electron acceptors (such as chloranil, tetracyanobenzene, tetracyanoquinodimethane, etc.) readily establish enol silyl ethers to be excellent electron donors. The deliberate irradiation of the diagnostic (red) charge-transfer absorption bands of the EDA complexes of enol silyl ethers and TNM at -40 degrees C affords directly the same alpha-nitro ketones, under conditions in which the thermal reaction is too slow to compete. A common pathway is discussed in which the electron transfer from the enol silyl ether (ESE) to TNM results in the radical ion triad [ESE(*)(+), NO(2)(*), C(NO(2))(3)(-)]. A subsequent fast homolytic coupling of the cation radical of the enol silyl ether with NO(2)(*)() leads to the alpha-nitro ketones. The use of time-resolved spectroscopy and the disparate behavior of the isomeric enol silyl ethers of alpha- and beta-tetralones as well as of 2-methylcyclohexanone strongly support cation radicals (ESE(*)(+)) as the critical intermediate in thermal and photoinduced electron-transfer as described in Schemes 1 and 2, respectively.     

Photochemical Selective Desilylation of t-Butyldimethylsilyl Ethers

The silyl moiety, e.g., trimethylsilyl (TMS), has been widely used as a protecting group for alcohols or aldehydes and ketones in organic synthesis via formation of alkyl silyl ethers or enol silyl ethers respectively. Generally, the protecting silyl group was removed by fluoride ion1, acid2 or base3. However, these deprotection methods afford little selectivity between silyl alkyl ethers and silyl enol ethers. Recently, photochemical approaches of desilylation have also been developed4-7. K…     

Acid anhydrides as alternatives to acid chlorides in the palladium‐catalyzed reaction with silacyclobutanes

The palladium‐catalyzed reaction of acid anhydrides with silacyclobutane gives a mixture of cyclic silyl enol ether, carboxy(propyl)silane, and 3‐(carboxysilyl)ketone. In the presence of N,N‐dicyclohexylcarbodiimido (DCC), the reaction preferentially provides a cyclic silyl enol ether in a good yield. In addition, the palladium‐catalyzed reaction of benzoic acid with silacyclobutane in the presence of two equivalents of DCC also affords a cyclic silyl enol ether in a moderate yield. Copyright © 2001 John Wiley & Sons, Ltd.     

Synthesis of Telechelic Oligo(isobutyl vinyl ether)s via Alkylation of Silyl Enol Ethers by the Propagating Chain End in an Ab Initio Cationic Polymerisation

Telechelic oligomers prepared by cationic polymerisation of isobutyl vinyl ether were synthesised by an ab initio procedure, in which silyl enol ethers were alkylated by the propagating carbocationic chain end. In‐situ addition of a silyl enol ether to the propagating chain end in a cationic polymerisation yields functionalized oligomers during the polymerisation. Therefore, it is not necessary to operate under living conditions.     

Synthesis of a chiral steroid ring D precursor starting from carvone

A chiral five-membered, silyl enol ether containing, steroid ring D precursor has been synthesized from carvone. This silyl enol ether has been applied in the synthesis of a chiral C17 functionalized steroid skeleton using the addition of a carbocation, generated with ZnBr₂ from a Torgov reagent, followed by cyclization of the adduct by treatment with acid.     

The mannich reaction-II : Derivatization of aldehydes and ketones using dimethyl(methylene)ammonium salts

Aldehydes and ketones have been converted efficiently to their corresponding Mannich products by various dimethyl(methylene)ammonium salts under a range of reaction conditions. The several methods used to form these derivatives are compared. Excellent approaches to aldehyde derivatives involve treating the enol silyl ether of the carbonyl compound with methyllithium and then an iminium salt, or directly adding the iminium salt to the enol silyl ether. Ketones may be derivatized effectively by treatment with potassium hydride, followed by an iminium salt, or from the enol silyl ether by addition of the iminium reagent. Use of iminium reagents in the Mannich reaction is recommended because the yields are often good and the site of attachment on an unsymmetrical ketone is both predictable and controllable.     

Abnormal Ito-Saegusa oxidation of TIPS enol ether assisted by a hydroxy group on a side chain

Although Ito-Saegusa oxidation gives defined α,β-unsaturated ketones from silyl enol ether of ketones controlled by the position of the sp² carbon of the silyl enol ether, the formation of a regioisomeric product that was oxidized abnormally was observed. The structural requirements for the substrates, the conditions, and a plausible mechanism are presented.     

Mechanistic investigation of substrate oxidation by Ce(IV) reagents in acetonitrile

Rates and activation parameters for the Ce(4+)-mediated oxidation of a beta-keto ester, a beta-diketone, and a beta-keto silyl enol ether were determined in acetonitrile. In the case of the dicarbonyls, the enol content of the substrate impacts the rate of oxidation by Ce(4+), predominantly through contributions from DeltaH(). For the silyl enol ether, the transition state for oxidation by Ce(4+) is substantially more ordered than it is for the beta-keto ester or the beta-diketone.     

Stereoselective synthesis of cis-2,5-disubstituted THFs: application to adjacent bis-THF cores of Annonaceous acetogenins

The iodocyclization of γ,δ-unsaturated alcohols in the presence of a silyl enol ether produced cis-2,5-disubstituted tetrahydrofurans in one pot via siloxy intermediates. N-Iodosuccinimide (NIS) effectively worked as an activator of the double bonds in the substrates and the silyl enol ether. Application to an expedient synthesis of the adjacent bis-tetrahydrofuran core of Annonaceous acetogenins with a cis/threo/cis relative stereochemistry is also described.     

Cyclooctanone synthesis via a formal [6+2] cycloaddition reaction of a dicobalt acetylene complex

An efficient formal [6+2] cycloaddition reaction of a new six-carbon unit with enol silyl ether was developed on the basis of a dicobalt hexacarbonyl propargyl cation species. Under the influence of EtAlCl₂, 6-benzoyloxy-2-(triisopropylsilyloxy)-1-hexen-4-yne-dicobalthexacarbonyl reacted with enol triisopropylsilyl ethers to yield 7-(triisopropylsilyloxy)-3-cyclooctyn-1-one-dicobalthexacarbonyl derivatives in good yield. The reactions with cyclic enol silyl ethers as well as acyclic enol silyl ethers exhibited remarkably high diastereoselectivity.     

Domino Mukaiyama-Michael reactions in the synthesis of polycyclic systems

Good results were obtained in the Mukaiyama-Michael reaction of the silyl enol ether of cyclohexanone with 2-methyl-2-cyclopentenone and carvone, with transfer of the silyl group to the receiving enone and with TrSbCl₆ as catalyst. A second Mukaiyama-Michael reaction of this new silyl enol ether with methyl vinyl ketone and cyclization of the resulting adduct leads to tricyclic compounds in one-pot domino sequences. The scope and limitations of this domino reaction have been investigated.     

Synthesis and PET oxidative cyclization of silyl enol ethers: build-up of quasi-steroidal carbocycles

PET oxidative cyclization of silyl enol ethers carrying suitable side chains with olefinic double bonds results in the stereoselective formation of carbocycles. Two model compounds for investigating the influence of silyl enol ether ring size are synthesized. Furthermore the synthesis of a quasi-steroidal carbocycle with an unnatural configuration is presented.