Suzuki coupling reactions of 2,4,6-trialkoxyphenylboronic acids with enol triflates: asymmetric synthesis of a lactone template for calyxin assemblage

Suzuki coupling reactions between 2,4,6-trialkoxyphenylboronic acids and enol triflates have been found to occur in excellent yield, while the use of an enol tosylate failed to give any of the desired product. This coupling reaction has led to the synthesis of a lactone which could serve as a precursor to several calyxin analogues.     

5-(Trimethylstannyl)-2H-pyran-2-one and 3-(Trimethylstannyl)-2H-pyran-2-one: New 2H-Pyran-2-one Synthons

5-(Trimethylstannyl)-2H-pyran-2-one (11) and 3-(trimethylstannyl)-2H-pyran-2-one (30), readily prepared from the corresponding bromo-2H-pyran-2-ones, undergo Pd(0)-catalyzed coupling reactions with a variety of enol triflates to give 5- and 3- substituted 2H-pyran-2-ones, respectively. This reaction is applicable to the enol triflates of 14beta-hydroxy-17-ketosteroids, and therefore may prove useful in convergent syntheses of lucibufagins and bufadienolides.     

Palladium-catalyzed amidation of enol triflates: a new synthesis of enamides

[reaction: see text] The palladium-catalyzed coupling of a range of enol triflates with amides, carbamates, and sulfonamides has been developed. This offers a simple and widely applicable synthesis of enamides, which may not be readily available by other means.     

Synthesis of substituted pyrazoles via tandem cross-coupling/electrocyclization of enol triflates and diazoacetates

The synthesis of 3,4,5-trisubstituted pyrazoles via a tandem catalytic cross-coupling/electrocyclization of enol triflates and diazoacetates is presented. The initial scope of this methodology is demonstrated on a range of differentially substituted acyclic and cyclic enol triflates as well as an elaborated set of diazoacetates to provide the corresponding pyrazoles with a high degree of structural complexity.     

Synthesis of Unsaturated Tricyclic Lactones. The Coupling of the Enol Triflate of β-Keto Lactones with Lithium Dimethylcuprate

The anions of selected β-keto lactones were transformed into their corresponding enol triflates. These enol triflates were coupled with lithium dimethylcuprate to afford tricyclic unsaturated /aciones, key intermediates for the synthesis of the biologically important natural product forskolin.     

An olefin metathesis route for the preparation of (1-->6)-linked C-disaccharide glycals. A convergent and flexible approach to C-saccharide synthesis

A convergent route to a variety of C-1-disaccharide glycals based on the olefin metathesis reaction of enol ethers and alkenes is described. The DCC-mediated coupling reaction of a variety of pentose enitols (1a-c) with a number of C-5- and C-6-monosaccharide carboxylic acids (2a-e) gave the corresponding esters 3a-l in good yield. Methylenation of these compounds was followed by ring-closing metathesis, mediated by the Schrock molybdenum catalyst 8 in warm toluene, to provide the target C-disaccharide glycals 5a-l. The formed enol ether double bond in 5a was then transformed, via standard manipulations, into a variety of C-disaccharide derivatives 21-25.     

Vinyl carbocations: solution studies of alkenyl(aryl)iodonium triflate fragmentations

Generation of vinyl cations is facile by fragmentation of alkenyl(aryl)iodonium trifluoromethanesulfonates. Kinetics and electronic effects were probed by (1)H NMR spectroscopy in CDCl(3). Products of fragmentation include six enol triflate isomers in addition to iodoarenes. The enol triflates arise from direct reaction of a triflate anion with the starting iodonium salts as well as triflate reaction with rearranged secondary cations derived from those salts. G2 calculations of the theoretical isodesmic hydride-transfer reaction between secondary vinyl cation 7 and primary vinyl cation 6 reveal that cation 6 is 17.8 kcal/mol higher in energy. Activation parameters for fragmentation of (Z)-2-ethyl-1-hexenyl(3,5-bis-trifluoromethylphenyl)iodonium triflate, 17e, were calculated using the Arrhenius equation: E(a) = 26.8 kcal/mol, Delta H(++) = 26.2 kcal/mol, and Delta S(++) = 11.9 cal/mol x K. Added triflate increases the rate of fragmentation slightly, and it is likely that for most beta,beta-dialkyl- substituted vinylic iodonium triflates enol triflate fragmentation products are derived from three competing mechanisms: (a) vinylic S(N)()2 substitution; (b) ligand coupling (LC); and (c) concerted aryliodonio departure and 1,2-alkyl shift leading to secondary rather than primary vinyl cations.     

Synthesis of cyclobutanones and four-membered enol ethers by using a rearrangement reaction of enol triflates

A new synthetic method of cyclobutanone derivatives and four-membered enol ethers via an intramolecular cyclization of a ketone enolate was developed. The cyclization precursors, enol triflates having a silyloxy group at the β′-position, were synthesized from the corresponding β-hydroxy ketones, which were prepared via an aldol reaction of a cycloalkanone and an aldehyde. Under the influence of TBAF, the enol triflates afforded a cyclobutanone or a four-membered enol ether through rearrangement of the trifluoromethanesulfonyl group followed by an intramolecular C- or O-alkylation reaction.     

Nickel-catalyzed carbonylative Negishi cross-coupling reactions

Catalytic carbonylative Negishi cross-coupling reactions are described. This method readily provides various enones from enol triflates and diorganozinc reagents with catalytic amounts of nickel(II) chloride-4,4′-dimethoxyl-2,2′-bipyridyl under carbon monoxide atmosphere. The rate of carbon monoxide insertion is increased by the addition of lithium or magnesium halides and the use of polar solvents. Alkenyl iodides can also be used in place of enol triflates.     

Unexpected migration and oxidative cyclization of substituted 2-acetophenone triflates under basic conditions: synthetic and mechanistic insights

Oxidative ring closure of alkyl-substituted 2-hydroxyacetophenone trifluoromethanesulfonate esters (triflates) occurs upon exposure to base in anaerobic DMF at 20-90 degrees C. Alkyl substitution is required for ring closure. A migrated enol triflate product forms at lower temperature in high yield via migration of the trifluoromethanesulfonate in the unsubstituted and monoalkyl-substituted cases. The alkyl-substituted enol triflates also enter into the benzofuran-3-one ring-forming process under thermal cyclization conditions. Potential mechanistic pathways are evaluated.     

Hydrogenolysis of enol triflates; A new method for the reduction of ketones to methylene compounds

Hydrogenolysis of enol trifluoromethanesulphonates (enol triflates) gives the hydrocarbon in high yield; ketones can thus be converted to the corresponding methylene compounds in a two-step process under mild conditions.     

Terminal olefins from aldehydes through enol triflate reduction

The transformation of aldehydes into terminal olefins through reduction of the corresponding enol triflates is described. The method is effective with both linear and alpha-branched aldehydes.     

Suzuki cross-coupling reactions of gamma-alkylidenebutenolides: application to the synthesis of vulpinic acid

alpha-Hydroxy-gamma-alkylidenebutenolides were efficiently functionalized by Suzuki cross-coupling reactions via the corresponding enol triflates. The natural product vulpinic acid was prepared by this methodology.     

Palladium-catalyzed carbonylation of enol triflates. A novel method for one-carbon homologation of ketones to α,β-unsaturated carboxylic acid derivatives

Ketones can be homologated to α,gb-unsaturated esters or amides via their enol triflates by a palladium-catalyzed reaction with carbon monoxide and alcohols or amines.     

Coupling reactions of alpha-(N-carbamoyl)alkylcuprates with enol triflates derived from cyclic beta-keto esters: A facile approach to gamma-carbamoyl-alpha,beta-enoates

alpha-(N-Carbamoylalkyl)cuprates couple with enol triflates derived from carbocyclic and heterocyclic (i.e., piperidinones) beta-keto esters. Product yields are higher with the alkyl(cyano)cuprates [i.e., RCu(CN)Li, 56-93%] than with the dialkylcuprate reagents (i.e., R(2)CuLi.LiCN). An enol nonaflate works as well as the corresponding enol triflate. A facile synthetic route to gamma-amino alpha,beta-enoates not readily prepared from gamma-keto-alpha,beta-enoates is thus established. The gamma-amino-alpha,beta-enoates, available via N-Boc deprotection, can be cyclized to annulated pyrrolin-2-ones.     

Development of a Friedel-Crafts triflation

The development of a new variant of the Friedel-Crafts reaction that yields 3-aryl enol triflates is described. The reaction is practical, is atom-economical, and works well with electron-rich arene substrates. [reaction: see text].     

Enol triflates derived from the Wieland-Miescher ketone and an analog bearing an angular acetoxymethyl group: their highly regioselective synthesis and Stille coupling with vinyl(tributyl)tin

A highly selective synthesis of the enol triflate derived from the 9-keto group was achieved directly from the Wieland-Miescher ketone or an analog in kinetic conditions with LHMDS/THF-HMPA and Comins reagent. The other isomeric triflates were also obtained selectively in other conditions and their specific Stille coupling with vinyl(tributyl)tin was achieved in high yields. The structures of the different isomers were determined unambiguously by IR, UV, ¹H and ¹³C NMR (COSY, HMBC, HSQC, and NOE). The results previously reported by Pal for the Wieland-Miescher ketone have therefore to be corrected, due to erroneous structural assignments.     

Coupling Reaction of Enol Derivatives with Silyl Ketene Acetals Catalyzed by Gallium Trihalides

A cross‐coupling reaction between enol derivatives and silyl ketene acetals catalyzed by GaBr₃ took place to give the corresponding α‐alkenyl esters. GaBr₃ showed the most effective catalytic ability, whereas other metal salts such as BF₃?OEt₂, AlCl₃, PdCl₂, and lanthanide triflates were not effective. Various types of enol ethers and vinyl carboxylates as enol derivatives are amenable to this coupling. The scope of the reaction with silyl ketene acetals was also broad. We successfully observed an alkylgallium intermediate by using NMR spectroscopy, suggesting a mechanism involving anti‐carbogallation among GaBr₃, an enol derivative, and a silyl ketene acetal, followed by syn‐β‐alkoxy elimination from the alkylgallium. Based on kinetic studies, the turnover‐limiting step of the reaction using a vinyl ether and a vinyl carboxylate involved syn‐β‐alkoxy elimination and anti‐carbogallation, respectively. Therefore, the leaving group had a significant effect on the progress of the reaction. Theoretical calculations analysis suggest that the moderate Lewis acidity of gallium would contribute to a flexible conformational change of the alkylgallium intermediate and to the cleavage of the carbon?oxygen bond in the β‐alkoxy elimination process, which is the turnover‐limiting step in the reaction between a vinyl ether and a silyl ketene acetal.     

Carbohydrate-based oxepines: ring expanded glycals for the synthesis of septanose saccharides

A ring-closing metathesis (RCM) approach to a family of carbohydrate-based oxepines is described. A variety of readily accessible, protected monosaccharide derived dienes were used to demonstrate the utility of the synthetic sequence and to investigate how factors such as rigidification and deoxygenation mediate RCM using the Grubbs or Schrock catalyst. The seven-membered cyclic enol ethers are ring expanded glycals to be used in the synthesis of septanose carbohydrates.     

Efficient synthesis of benzopyrano[2,3-b]pyridines by sequential reactions of 1,3-bis-silyl enol ethers with 3-cyanobenzopyrylium triflates

Benzopyrano[2,3-b]pyridines were efficiently prepared by condensation of 1,3-bis-silyl enol ethers with 3-cyanobenzopyrylium triflates and subsequent domino ‘retro-Michael-lactonization-aldol’ reactions.