Sulfur ylides via decarboxylation of carboxymethylsulfonium betaines: a novel and mild protocol for the preparation of oxiranes

A novel protocol for the generation of sulfur ylides is described. The overall process involves thermal decarboxylation of a carboxymethylsulfonium betaine to give a sulfur ylide that, in the presence of an aldehyde, affords the corresponding terminal oxirane. Yields were found to correlate with the electron deficiency of the aryl aldehyde. In situ generation of betaine in the presence of an aldehyde successfully afforded the desired oxirane in moderate yield, thus demonstrating the feasibility of a catalytic process. [reaction: see text]     

Redesigning the mechanism of the lipase-catalysed aminolysis of esters

In a previous work, several 2-phenylcycloalkanamines were subjected to aminolysis catalysed by the lipase B from Candida antarctica (CAL-B). In these processes, the size of the cycle and the stereochemistry of the stereogenic centres of the amines had a strong influence on both the enantiomeric ratio and the reaction rate. Herein, molecular modelling approaches have been used to revise the lipase-catalysed aminolysis mechanism. Thus, complexes of CAL-B with the phosphonamidate analogues related to substrates in the kinetic resolution of several 2-phenylcycloalkanamines by this enzyme were built and minimised. This computational study suggests the formation of zwitterionic species (named TI-Z), resulting from the direct His-unassisted attack of the amine onto the carbonyl group of the acyl-enzyme, as the most plausible intermediate for the CAL-B-catalysed aminolysis. This proposal differs slightly from the commonly accepted serine-mediated mechanism, where removal of the proton from the amine occurs simultaneously to the nucleophile attack to the acyl-enzyme complex (TI-2). Subsequently, His-assisted deprotonation of the resulting ammonium group takes place, and a molecule of water could be necessary in some cases to facilitate the transfer of the proton to the catalytic histidine.     

Phosphorus pentasulfide: A mild and versatile Catalyst/Reagent for the preparation of dithiocarboxylic esters

The reaction of carboxylic acids (1) with a variety of thiols or alcohols in the presence of phosphorus pentasulfide (P(4)S(10)) as a catalyst and reagent (20-40 mol %) proceeded effectively to afford the corresponding dithiocarboxylic esters (2) in high yields.     

Intramolecular general acid catalysis in the aminolysis of beta-lactam antibiotics

The rate of aminolysis of benzylpenicillin and cephaloridine by hydroxylamine, unlike other amines, shows only a first order dependence on amine concentration. The rate enhancement compared with that predicted from a Bronsted plot for other primary amines with benzylpenicillin is greater than 10(6). This is much more than an alpha-effect and is compatible with rate-limiting formation of the tetrahedral intermediate due to a rapid intramolecular general acid catalysed breakdown of the intermediate. For cephaloridine, the rate enhancement is greater than 10(4) which demonstrates that beta-lactam C-N bond fission and expulsion of the leaving group at C3' are not concerted.     

Enzymatic synthesis of N-acylethanolamines: direct method for the aminolysis of esters

Immobilized Candida antarctica (Novozyme 435) catalyzed synthesis of N-acylethanolamines is described. Treatment of methyl esters with lipase and amines yielded the desired amides within 2-24 h with yields ranging from 41% to 98%.     

Lewis acid catalyzed reaction of arylvinylidenecyclopropanes with acetals: a facile synthetic protocol for the preparation of indene derivatives

[Structure: see text] A number of highly substituted indene derivatives have been prepared in good yields by the reactions of arylvinylidenecyclopropanes 1 with acetals 2 in the presence of Lewis acid under mild conditions. The reaction is believed to proceed via regioselective addition of oxonium intermediate to arylvinylidenecyclopropane and the subsequent intramolecular Friedel-Crafts reaction.     

Lewis acid mediated reactions of 1-cyclopropyl-2-arylethanones with allenic esters: a facile synthetic protocol for the preparation of dihydrofuro[2,3-h]chromen-2-one derivatives

TMSOTf-mediated reactions of 1-cyclopropyl-2-arylethanones with allenic esters afford a novel method for the synthesis of dihydrofuro[2,3-h]chromen-2-one derivatives in moderate to good yields. This process is a sequential reaction involving a nucleophilic ring-opening reaction of the cyclopropane by H(2)O, two intermolecular aldol-type reactions and one intramolecular aldol-type reaction, a cyclic transesterification, dehydration, and aromatization mediated by Lewis acid.     

Intramolecular carbolithiation reactions for the preparation of Azabicyclo

Tin-lithium exchange and intramolecular carbolithiation (anionic cyclization) have been used to construct the three nitrogen-positional isomers of the azabicyclo[2.2.1]heptane ring system. The 7-azabicyclo[2.2.1]heptane ring system is accessed from either diastereomer of a 2,5-disubstituted pyrrolidine, via a chiral organolithium intermediate. The 2-azabicyclo[2.2.1]heptane ring system is formed stereoselectively in low yield by a tandem cyclization, together with the product from monocyclization. Better yields of the 2-aza ring system can be obtained using an alternative approach from a 2-tributylstannyl-4-allylpyrrolidine, despite the trans arrangement of the tin (and, hence, lithium) atom and the allyl unit. The 1-azabicyclo[2.2.1]heptane ring system is accessed in just three steps from 4-piperidone.     

Catalyzed hydroboration of nitrostyrenes and 4-vinylaniline: a mild and selective route to aniline derivatives containing boronate esters

Transition metal catalyzed reactions of catecholborane (HBcat; cat = 1,2-O₂C₆H₄) with β-nitrostyrene and 3-nitrostyrene lead to products derived from competing hydrogenation and hydroboration of the alkene unit along with reduction of the nitro group. Hydroboration of 4-vinylaniline gave regioselective formation of either the branched or the linear organoboronate ester depending upon the catalyst precursors (i.e., RhCl(PPh₃)₃ or Rh(acac)(dppe) vs [Cp^∗IrCl₂]₂) used to facilitate this reaction. Hydroboration products were converted to air-stable primary amines by addition of pinacol.     

Intramolecular carbolithiation reactions for the preparation of 3-alkenylpyrrolidines

Tin-lithium exchange allows the formation of alpha-amino-organolithium species that undergo anionic cyclization onto allylic ethers to give 3-alkenylpyrrolidines. The methodology has been applied to the synthesis of an advanced intermediate related to the natural product (-)-alpha-kainic acid.     

A mild and environmentally acceptable synthetic protocol for chemoselective α-bromination of β-keto esters and 1,3-diketones

A wide variety of unsubstituted β-keto esters can be brominated chemoselectively to the corresponding α-monobromo-β-keto esters by using a combination of vanadium pentoxide, hydrogen peroxide and ammonium bromide in a biphasic system, dichloromethane-water at 0-5 °C. In addition, α-mono substituted β-keto esters, cyclic β-keto-esters and 1,3-diketones can also be brominated selectively using the same protocol.     

Polymeric DABCO-bromine complex: a mild oxidant for the preparation of ketones and aldehydes

A stable, shelf-ready polymeric oxidant was prepared from the addition of Br₂ to DABCO in CCl₄. This material was used to convert simple primary and secondary alcohols to the corresponding aldehydes and ketones in biphasic CH₂Cl₂/H₂O.     

Kinetics of aminolysis for 1-thio-β- D-glucopyranosyl esters of N-acylalanines

The kinetics of aminolysis of 1-thio-β-D-glucopyranosyl esters of N-protected alanines (1) in dichloromethane, at 26°, by ethyl glycinate, under pseudo-first-order conditions follows the relationship k-_obsd = k₂[H-Gly-OEt]. Significant differences were observed in the rates of dipeptide forming aminolysis for 1-thiolesters 1a-1f, depending on N-acyl substituents and the configuration of alanine.     

High-yielding macrocyclization conditions used in the synthesis of novel Sansalvamide A derivatives

Described are the syntheses of nine Sansalvamide A derivatives using new, high-yielding, in situ deprotection-cyclization conditions that are general for this series of macrocycles, 55% average for both steps. This is 10-fold greater than previously reported yields.