Metal nitrite: a powerful oxidizing reagent

An efficient and simple source of nitroso reagents and their oxidation reactions are described. The combination of a Lewis acid and a metal nitrite was applied to the oxidation of silyl enol ethers. Amino acid and peptide derivatives were easily accessed through in situ C-C bond cleavage of fully substituted silyl enol ethers upon oxidation.     

Stereoselective synthesis of cycloheptanone derivatives via an intermolecular [5 + 2] cycloaddition reaction

[reaction: see text] A [5 + 2] cycloaddition reaction of a new five-carbon unit was developed on the basis of a dicobalt hexacarbonyl propargyl cation species. Under the influence of EtAlCl(2), [5-benzoyloxy-2-(triisopropylsiloxy)-1-penten-3-yne)]dicobalt hexacarbonyl reacted with enol triisopropylsilyl ethers to yield seven-membered dicobalt acetylene complexes in good yield. The reactions with cyclic enol silyl ethers as well as acyclic enol silyl ethers exhibited remarkably high diastereoselectivity. The cycloadducts can be easily converted into various kinds of cycloheptanone derivatives.     

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.     

A Chiral N,N′‐Dioxide–ZnII Complex Catalyzes the Enantioselective [2+2] Cycloaddition of Alkynones with Cyclic Enol Silyl Ethers

A highly efficient enantioselective [2+2] cycloaddition between alkynones and cyclic enol silyl ethers was developed by using a chiral N,N′‐dioxide‐zinc(II) complex as a catalyst. This method functions well for a variety of terminal alkynes as well as cyclic enol silyl ethers, with good to excellent enantioselectivity (up to 97 % ee). This is also the first successful example for the catalytic enantioselective [2+2] cycloaddition of internal alkynes with cyclic enol silyl ethers to give fully substituted cyclobutenes. Meanwhile, the desired cyclobutene product can easily be transformed into fused cyclobutane derivatives.     

Tandem carbocupration/oxygenation of terminal alkynes

[chemical reaction: see text]. A direct and general synthesis of alpha-branched aldehydes and their enol derivatives is described. Carbocupration of terminal alkynes and subsequent oxygenation with lithium tert-butyl peroxide generates a metallo-enolate. Trapping with various electrophiles provides alpha-branched aldehydes or stereo-defined trisubstituted enol esters or silyl ethers. The tandem carbocupration/oxygenation tolerates alkyl and silyl ethers, esters, and tertiary amines. The reaction is effective with organocopper complexes derived from primary, secondary, and tertiary Grignard reagents and from n-butyllithium.     

Synthetic Studies on and Mechanistic Insight into [W(CO)5(L)]‐Catalyzed Stereoselective Construction of Functionalized Bicyclo[5.3.0]decane Frameworks

Stereoselective preparation of a variety of synthetically useful functionalized bicyclo[5.3.0]decane derivatives was achieved by tandem cyclization of 3‐siloxy‐1,3,9‐triene‐7‐yne derivatives based on the electrophilic activation of alkynes catalyzed by [W(CO)₅(L)]. The reaction proceeded smoothly under photoirradiation, and various substrates were cyclized to give the corresponding bicyclic compounds with up to four chiral centers stereospecifically. Reactions of siloxydienes with a silyl substituent as an equivalent of a hydroxyl group also proceeded with wide generality to afford silyl‐substituted bicyclo[5.3.0]decanes, which were highly useful as synthetic intermediates. Stereochemical studies concerning the silyl enol ether moiety suggested that two types of reaction pathway for the formation of seven‐membered rings were present. The reaction of (Z)‐enol silyl ethers proceeded through Cope rearrangement of cis‐divinylcyclopropane intermediates, and that of (E)‐enol silyl ethers by 1,4‐addition of the dienyl tungsten species at the position δ to the metal atom. In the reactions of siloxydiene derivatives with silyl substituents, all possible diastereomers could be synthesized stereoselectively by changing the geometry of the silyl enol ether and enyne moieties.     

Chiral Zinc(II)‐Catalyzed Enantioselective Tandem α‐Alkenyl Addition/Proton Shift Reaction of Silyl Enol Ethers with Ketimines

A new catalytic asymmetric tandem α‐alkenyl addition/proton shift reaction of silyl enol ethers with ketimines was serendipitously discovered in the presence of chiral N,N′‐dioxide/Zn^II complexes. The proton shift preferentially proceeded instead of a silyl shift after α‐alkenyl addition of silyl enol ether to the ketimine. A wide range of β‐amino silyl enol ethers were synthesized in high yields with good to excellent ee values. Control experiments suggest that the Mukaiyama–Mannich reaction and tandem α‐alkenyl addition/proton shift reaction are competitive reactions in the current catalytic system. The obtained β‐amino silyl enol ethers were easily transformed into β‐fluoroamines containing two vicinal tetrasubstituted carbon centers.     

A novel synthesis of silyl enol ethers from α-silylbenzylthiols and carboxylic acid derivatives via C---C bond formation; thermal rearrangement of S-α-silylbenzyl thioesters

A new procedure for the synthesis of silyl enol ethers from S-α-silylbenzyl thioesters without need for either bases or catalysts via C---C bond formation is described. Solutions of S-α-silylbenzyl thioesters were simply heated at 180°C for 24 h in a sealed tube to give silyl enol ethers in good yields with high stereoselectivity. Cyclization of the dipoles generated by thermal rearrangement of the silyl group and elimination of sulfur afforded silyl enol ethers.     

Condensation of enol silyl ethers with 2-acetoxytetrahydrofuran and -tetrahydropyrans

Trimethylsilyl trifluoromethanesulfonate catalyzes stereoselective condensation of enol silyl ethers and 2-acetoxytetrahydrofuran or -tetrahydropyran derivatives.     

Efficient synthesis of salicylates by catalytic [3 + 3] cyclizations of 1,3-bis(silyl enol ethers) with 1,1,3,3-tetramethoxypropane

Salicylic acid derivatives were prepared by Me3SiOTf-catalyzed [3 + 3] cyclization of 1,3-bis(silyl enol ethers) with 1,1,3,3-tetramethoxypropane.     

Facile synthesis of pyrroles via Rh(II)-catalyzed transannulation of 1-tosyl-1,2,3-triazoles with silyl or alkyl enol ethers

A novel Rh(II)-catalyzed transannulation of 1-tosyl-1,2,3-triazoles with silyl or alkyl enol ethers has been developed, which enables the facile synthesis of substituted pyrroles in a regiocontrollable manner. Moreover, the methodology could be extended to access 3-pyrrolin-2-one derivatives with silyl ketene acetals used as the reaction partner.     

Tandem asymmetric conjugate addition--silylation of enantiomerically enriched zinc enolates. Synthetic importance and mechanistic implications

[formula: see text] The zinc enolates, resulting from the copper-catalyzed enantioselective conjugate addition of dialkyl zinc reagents to cyclic and acyclic enones, could be trapped, quantitatively, as silyl enol ethers with TMSOTf in apolar solvents or with TMSCI and NEt3. These enantiomerically enriched silyl enol ethers were submitted to four synthetic transformations to show their synthetic utility. The zinc enolates obtained from acyclic enones were found to be configurationally stable, as shown by the stereochemistry of the silyl enol ethers.     

Formal [4+2] cycloaddition between 3-ethoxycyclobutanones and silyl enol ethers

3-Ethoxycyclobutanones reacted with silyl enol ethers to give formal [4+2] cycloadducts, 3-ethoxy-5-trimethylsiloxycyclohexanone derivatives, by using ethylaluminum dichloride as a Lewis acid. Highly oxygenated cyclohexanone derivatives were stereoselectively prepared by this method.     

Synthesis and reactivity of N-alkyl-2-oxoalkanesulfonamides

A series of N-alkyl-2-oxoalkanesulfonamides have been synthesized by reacting silyl enol ethers with N-alkyl-sulfamoyl chlorides. Their reactivity towards electrophiles was investigated in order to explore the regio-aand stereoselectivity of the process. 2-Oxoalkanesulfonamides were used to prepare 5-(methylsulfamoyl)-1,4-dihydropyridines derivatives.     

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.     

Origins of aryl substituent effects on the stereoselectivities of additions of silyl enol ethers to a chiral oxazolinium ion

Density functional theory calculations are reported that reveal the role of aromatic interactions in the additions of aryl-substituted silyl enol ethers to a chiral oxazolinium ion. Aryl-substituted silyl enol ethers give the opposite diastereomer of the adduct than do aliphatic silyl enol ethers, due to a combination of attractive cation-π and CH-π interactions, reduced steric repulsion, and lower torsional strain in the more "crowded" transition state.     

Novel carbon-carbon bond-forming reactions using carbocations produced from substituted propargyl silyl ethers by the action of TMSOTf.

Highly useful carbon-carbon bond forming reactions using stable allenyl, propargyl, or allyl-propargyl hybrid cations have been developed. These carbocations could be generated from silyl 1-(pi-donor)-substituted propargyl ethers by the action of trimethylsilyl trifluoromethanesulfonate in dichloromethane at -78 degrees C to room temperature and could be attacked nucleophilically by electron rich arenes, allylsilanes, or enol silyl ethers, giving rise to allenes, alkynes, and their derivatives. A novel method for regio- and stereoselective synthesis of conjugated enynes utilizing allyl-propargyl hybrid cations has also been established.     

Studies on Reactivity of Pyridinium Chlorochromate — Iodine System: An Efficient Method for Converting Enol Silyl Ethers into α-Iodo Ketones

A new synthesis of α-iodo carbonyl derivatives is described. They are obtained, in very high yields, through an original and efficient procedure, by reaction of enol silyl ethers with I₂-PCC system.     

Synthesis of 1,3,5-tricarbonyl derivatives by condensation of 1,3-bis(silyl enol ethers) with acid chlorides

A variety of 1,3,5-tricarbonyl derivatives were prepared by reaction of 1,3-bis(silyl enol ethers) with acid chlorides under mild conditions. This includes reactions of both aromatic and aliphatic acid chlorides and bis(acid chlorides). The yields vary depending on the type of acid chloride employed.     

Preparation of proximal β-hydroxy silyl enol ethers from α,β-epoxyketones using silyllithium reagents

A new method for the stereoselective preparation of proximal β-hydroxy silyl enol ethers from α,β-epoxyketones using silyllithium reagents has been developed. The reaction is believed to proceed via Brook rearrangement assisted by opening of the adjacent epoxide. A number of α,β-epoxyketones were reacted with methyldiphenylsilyllithium to form the corresponding proximal β-hydroxy silyl enol ethers in good to excellent yield and excellent stereoselectivity.