One-pot enol silane formation-Mukaiyama aldol reactions: Crossed aldehyde-aldehyde coupling,thioester substrates,and reactions in ester solvents

Trimethylsilyl trifluoromethanesulfonate (TMSOTf) and a trialkylamine base promote both in situ enol silane/silyl ketene acetal formation and Mukaiyama aldol addition reactions between a variety of reaction partners in a single reaction flask. Isolation of the required enol silane or silyl ketene acetal is not necessary. For example, crossed aldol reactions between α-disubstituted aldehydes and non-enolizable aldehydes yield β-hydroxy aldehydes in good yield. In a related reaction, the common laboratory solvent ethyl acetate functions as both an enolate precursor and a green reaction solvent. When thioesters are employed as enolate precursors, high yields for additions to non-enolizable aldehydes are routinely observed.     

Rhodium-catalyzed α-fluoroalkylation reaction of ketones using silyl enol ethers

The treatment of silyl enol ethers with fluoroalkyl halides (R_f-X) in the presence of RhCl(PPh₃)₃ gave α-fluoroalkylated ketones. It seems that a rhodium complex derived from the silyl enol ether and RhCl(PPh₃)₃ played an important role for the oxidative addition of fluoroalkyl halides and the reductive elimination of the product.     

Synthesis of 3-substituted 2-cyclohexenones through umpoled functionalization

A new protocol to obtain 3-substituted 2-cyclohexenones, was developed by reversing the chemical reactivity of 2-cyclohexenone. One-pot synthesis of 3-substituted 2-cyclohexenones can be achieved by treatment of 3-phenylthiosilyl enol ether with a mixture of t-BuLi/HMPA that allows hydrogen-selective exchange in presence of reactive electrophiles such as aldehydes, ketones and alkyl halides. This affords the corresponding product in moderate overall yield, after silyl enol ether cleavage and concomitant thiophenol elimination initiated with TBAF.     

Zn-mediated rhodium-catalyzed α-trifluoromethylation of ketones via silyl enol ethers

The treatment of silyl enol ethers of ketones with CF₃-I and Et₂Zn in the presence of RhCl(PPh₃)₃ in DME gave α-trifluoromethyl ketones in good yields. The reaction can be widely applicable to silyl enol ethers derived from aliphatic or aromatic ketones. In the absence of the rhodium catalyst, the reaction was very slow and the yields were quite poor.     

Synthesis of racemic nitramine, isonitramine and sibirine

Condensation of enol ether 6 with methyl vinyl ketone led easily to ketoaldehyde 7 whose cyclisation afforded the azaspiranic enone 8, a key intermediate for the synthesis of the title alkaloids.     

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.     

Preparation of silyl polyenol ethers by carbonyl olefination of silyl esters

Silyl enol ethers were produced by the carbonyl olefination of silyl esters with titanium carbene complexes generated by the desulfurizative titanation of thioacetals. The regioselective preparation of silyl dienol and trienol ethers has been achieved by using unsaturated silyl esters and thioacetals.     

Reaction of acylsilanes with α-sulfinyl carbanions: regioselective synthesis of silyl enol ethers

The reaction of acylsilanes with α-sulfinyl carbanions such as α-lithioalkyl sulfoxide is described. The reaction proceeds to give silyl enol ethers preferentially through the initial formation of the α-silyl alkoxide intermediates. In particular, the products derived from enolizable acylsilanes were the regio-defined silyl enol ethers that cannot be obtained by usual enolization of the corresponding unsymmetrical ketones with base.     

Chalcone and cinnamate synthesis via one-pot enol silane formation-Mukaiyama aldol reactions of ketones and acetate esters

Aryl alkyl ketones, acetate esters, and acetamides undergo facile one-pot enol silane formation, Mukaiyama aldol addition, and dehydrosilyloxylation in the presence of an amine base and excess trimethylsilyl trifluoromethanesulfonate. The chalcone and cinnamate products are generally recovered in high yield. The relative stoichiometry of the trimethylsilyl trifluoromethanesulfonate and amine base reagents determines whether the reaction yields the β-silyloxy carbonyl product or the α,β-unsaturated carbonyl.     

A highly stereoselective approach to tetrasubstituted (E)-β-hydroxy silyl enol ethers by addition of aryl-substituted oxiranyl anions to acylsilanes

A highly stereoselective approach to tetrasubstituted (E)-β-hydroxy silyl enol ethers is described. The reaction proceeds via a sequential addition/[1,2]-Brook rearrangement/epoxide-opening process of aryl-substituted oxiranyl anions with acylsilanes.     

A new flexible synthesis of (D-homo) steroids

A short, flexible and efficient procedure has been developed for the synthesis of C17 substituted steroid skeletons and D-homo steroid skeletons using a ZnBr₂ catalysed coupling of a silyl enol ether containing ring D precursor with a Torgov type reagent, followed by acid catalysed cyclisation of the adducts to (D-homo) steroid skeletons.     

Synthesis of functionalized acetophenones by [3 + 3] cyclizations of 1,3-bis-silyl enol ethers with 2-acetyl-3-silyloxyalk-2-en-1-ones

The TiCl₄ mediated cyclization of 1,3-bis-silyl enol ethers with 2-acetyl-1-silyloxybut-1-en-3-one and 3-acetyl-4-silyloxypent-3-en-2-one, readily prepared from 3-formyl(acetylacetone) and triacetylmethane, afforded a variety of functionalized acetophenones.     

Aldol-additions t0eα- and β-alkoxy aldehydes: The effect of chelation on simple diastereoselectivity

The TiC1₄ or SnCl₄ mediated reaction of enol silanes with chiral α- and β-alkoxy aldehydes constitutes the only presently known, general way to perform aldol additions with chelation-control (asymmetric induction 90%). If the enol silane is prochiral, the additional stereoselection (simple diastereoselectivity) is surprisingly good. This unusual effect has been traced to syn-type of complexation of the aldehyde function.     

1-Phenylthio-3-vinyl-3-cyclohexenol, a new reagent for bis-annelation of silyl enol ethers

1-Phenylthio-3-vinyl-cyclohex-1-en-3-ol (2) has been synthesized and investigated as a new bis-annelation reagent for silyl enol ethers. Reagent 2 can be synthesized by a Grignard reaction of vinyl magnesium bromide with 3-phenylthiocyclohexenone. The reaction with silyl enol ethers takes place under Lewis acid catalysis and generally proceeds in good yields. The resulting phenylthiodienes can be hydrolyzed to enones, which have been cyclized in a homologous aldol reaction to polycyclic compounds.     

New synthesis of arcyriaflavin-A via silyl enol ether-mediated and Fischer indolisations

A new synthesis of the natural product arcyriaflavin-A is described. It was brought about through Diels-Alder cycloaddition and two indolisations based on silyl enol ether nucleophilic attack and Fischer processes.     

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.     

Facial selectivity and stereospecificity in the (4 + 3) cycloaddition of epoxy enol silanes

The scope of the (4 + 3) cycloaddition using epoxy enol silanes has been examined. Unhindered and nucleophilic dienes react to give the highest yields, but hindered dienes give rise to higher diastereoselectivities. Notably, the cycloaddition shows facial selectivity and stereospecificity for the stereochemistry of the epoxy enol silane.     

Synthesis of functionalized p-dihydrobenzoquinones and p-benzoquinones based on [3+3] cyclizations of 1,3-bis-silyl enol ethers

Functionalized mono-protected p-dihydrobenzoquinones were prepared by [3+3] cyclization of 1,3-bis-silyl enol ethers with 2-acyloxy-3-(silyloxy)alk-2-en-1-ones. Deprotection and oxidation of the products afforded the corresponding p-benzoquinones.     

Synthesis of (2S,3R)- and (2S,3S)-[3-H1]-proline via highly stereoselective hydrolysis of a silyl enol ether

A straightforward synthesis of (2S)-[3,3-²H₂]-proline 1c and (2S,3R)- and (2S,3S)-[3-²H₁]-proline, 1b and 1a, respectively, has been devised. The key step of the route to the latter compounds involves highly stereoselective hydrolysis of the silyl enol ethers 3 and 3a, respectively, with protonation (deuteriation) from the re-face of the silyl enol ether.     

Co-catalyzed autoxidation of alkene in the presence of silane. The effect of the structure of silanes on the efficiency of the reaction and on the product distribution

A systematic investigation of the structural effect of silanes on the Co-catalyzed reductive oxygenation of alkene in the presence of silane (Mukaiyama-Isayama reaction) showed that the efficiency of the reaction decreases with the increase of the steric bulk of the silanes. A similar trend was observed for the metal-exchange reaction between Co(III)-alkylperoxo complex and silane, too. The peroxidation of (S)-limonene, followed by deprotection of the derived silyl peroxides, provides a mixture of the corresponding monocyclic hydroperoxide 24 and the bicyclic one 25, the ratio being a marked function of the steric bulk of silanes.