Lewis Acid Promoter Research Articles

ChemInform Abstract: Ammonolysis of Anilides Promoted by Ethylene Glycol and Phosphoric Acid.

Ethylene glycol (EG) and phosphoric acid have been found to promote the ammonolysis of a variety of diverse anilides as well as N-aryl carbamate, phthalimide, and urea substrates in the absence of transition metals or other Lewis acid promoters.

A Mechanistic Study of the Lewis Base-Directed Cycloaddition of 2-Pyrones and Alkynylboranes

Significant rate enhancements in the Diels-Alder reaction of alkynes and 2-pyrones bearing a Lewis basic group are observed when a combination of alkynyltrifluoroborates and BF3·OEt2 is used. This process generates functionalized aromatic compounds with complete regiocontrol. The observed rate enhancement was studied by density functional theory methods and appears to originate from coordination of the diene substrate to a mixture of alkynylborane intermediates, followed by a Lewis acid-mediated product equilibration step. Evidence for this mechanism is presented, as is the enhanced promotion of the cycloaddition via the use of alternative Lewis acid promoters.

Unified View of Oxidative C–H Bond Cleavage and Sulfoxidation by a Nonheme Iron(IV)–Oxo Complex via Lewis Acid-Promoted Electron Transfer

Oxidative C-H bond cleavage of toluene derivatives and sulfoxidation of thioanisole derivatives by a nonheme iron(IV)-oxo complex, [(N4Py)Fe(IV)(O)](2+) (N4Py = N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine), were remarkably enhanced by the presence of triflic acid (HOTf) and Sc(OTf)3 in acetonitrile at 298 K. All the logarithms of the observed second-order rate constants of both the oxidative C-H bond cleavage and sulfoxidation reactions exhibit remarkably unified correlations with the driving forces of proton-coupled electron transfer (PCET) and metal ion-coupled electron transfer (MCET) in light of the Marcus theory of electron transfer when the differences in the formation constants of precursor complexes between PCET and MCET were taken into account, respectively. Thus, the mechanisms of both the oxidative C-H bond cleavage of toluene derivatives and sulfoxidation of thioanisole derivatives by [(N4Py)Fe(IV)(O)](2+) in the presence of HOTf and Sc(OTf)3 have been unified as the rate-determining electron transfer, which is coupled with binding of [(N4Py)Fe(IV)(O)](2+) by proton (PCET) and Sc(OTf)3 (MCET). There was no deuterium kinetic isotope effect (KIE) on the oxidative C-H bond cleavage of toluene via the PCET pathway, whereas a large KIE value was observed with Sc(OTf)3, which exhibited no acceleration of the oxidative C-H bond cleavage of toluene. When HOTf was replaced by DOTf, an inverse KIE (0.4) was observed for PCET from both toluene and [Ru(II)(bpy)3](2+) (bpy =2,2'-bipyridine) to [(N4Py)Fe(IV)(O)](2+). The PCET and MCET reactivities of [(N4Py)Fe(IV)(O)](2+) with Brønsted acids and various metal triflates have also been unified as a single correlation with a quantitative measure of the Lewis acidity.

Hydrogenation of Carboxylic Acids Catalyzed by Half-Sandwich Complexes of Iridium and Rhodium

A series of half-sandwich Ir and Rh compounds are demonstrated to be competent catalysts for the hydrogenation of carboxylic acids under relatively mild conditions. Of the structurally diverse group of catalysts tested for activity, a Cp*Ir complex supported by an electron-releasing 2,2'-bipyridine ligand was the most active. Higher activity was achieved with employment of Brønsted or Lewis acid promoters. Mechanistic studies suggest a possible reaction pathway involving activated carboxylic acid substrates. The hydrogenation reaction was shown to be general to a variety of aliphatic acids.

ChemInform Abstract: Tetrahydroquinolines by Lewis Acid‐Promoted Friedel—Crafts Cyclizations.

AbstractUse of FeCl3 as Lewis acid promoter proves to be superior for unsubstituted and alkyl‐substituted substrates, whereas more reactive AlCl3 is necessary for substrates possessing heteroatom functionality.

ChemInform Abstract: A New Strategy for Efficient Synthesis of Medium and Large Ring Lactones Without High Dilution or Slow Addition.

We have developed an efficient method for medium and large ring lactone synthesis by a conceptually different ring-expansion strategy. The design of an unprecedented ring conjunction mode of oxetene, combined with the appropriate choice of a Lewis acid promoter and an additive, constitutes the key components of the new process. Enabled by this new approach, the reaction does not require high dilution or slow addition.

A New Strategy for Efficient Synthesis of Medium and Large Ring Lactones without High Dilution or Slow Addition

We have developed an efficient method for medium and large ring lactone synthesis by a conceptually different ring-expansion strategy. The design of an unprecedented ring conjunction mode of oxetene, combined with the appropriate choice of a Lewis acid promoter and an additive, constitutes the key components of the new process. Enabled by this new approach, the reaction does not require high dilution or slow addition.

Chemical synthesis of a tetrasaccharide related to the repeating unit of the O-polysaccharide isolated from Salmonella enterica O59

The chemical synthesis of the tetrasachharide repeating unit of the O-polysaccharide of Salmonella enterica O59 in the form of its p-methoxyphenyl glycoside is reported. The total synthesis of the tetrasaccharide has been achieved through concise protecting group manipulations and stereoselective glycosylations via thioglycoside activation using La(OTf) 3 as a Lewis acid promoter in conjunction with N-iodosuccinimide. La(OTf) 3 was found to be a better alternative to the more traditional Lewis acid promoters such as TfOH or TMSOTf.

ChemInform Abstract: Efficient Synthesis of β‐Chlorovinylketones from Acetylene in Chloroaluminate Ionic Liquids.

AbstractChloroaluminate ionic liquid, generated in situ from AlCl3 and [bmpy]Cl, acts both as solvent and a Lewis acid promoter.

Hetero Diels–Alder reactions of acyl phosphonates: synthesis of glycosyl type phosphonates

We have prepared glycosyl type phosphonates via hetero Diels–Alder (HDA) reactions of acyl phosphonates with electron rich dienes. HDA reactions of acyl phosphonates with Danishefsky’s diene required thermal activation to yield the desired dihydropyranones in good yield (70–91%). The reactions with Brassard’s diene involved Lewis acid promotion to yield the corresponding lactones, though in moderate yield (33–69%).

La(OTf)3: An Efficient Promoter for Thioglycoside Activation in Conjunction with N-Iodosuccinimide

Use of La(OTf)3 as a Lewis acid promoter for N-iodosuccinimide-mediated activation of thioglycosides is reported. The glycosylation reactions proceeded smoothly with good to excellent yields and stereoselectivity.

ChemInform Abstract: Asymmetric Diels-Alder and Ene Reactions Promoted by a Ti(IV) Complex Bearing a C2-Symmetric Tridentate Ligand.

Abstract A new Ti(IV) complex obtained from the C 2 -symmetric amino diol (1 R ,5 R )-3-aza-3-benzyl-1,5-diphenyl pentan-1,5-diol, (1 R ,5 R )- 1 , is used effectively as a Lewis acid promoter in asymmetric Diels–Alder reactions. Using various Evans' oxazolidinones as dienophiles and cyclopentadiene as the diene high yields of the adducts with moderate enantioselectivity, under different reaction conditions are achieved. The effects of solvent, temperature and ligand on the enantioselectivity of the Diels–Alder products are reported. Molecular modelling studies provide an understanding of the diastereofacial selectivity of the Diels–Alder reactions. Asymmetric carbonyl-ene reactions between various glyoxylate esters and α-methyl styrene are also described.

The synthesis of chiral N-heterocyclic carbene–borane and –diorganoborane complexes and their use in the asymmetric reduction of ketones

Chiral N-heterocyclic carbene-borane complexes have been synthesised, and have been shown to reduce ketones with Lewis acid promotion. Chiral N-heterocyclic carbene-borane and -diorganoborane complexes can reduce ketones with enantioselectivities up to 75% and 85% ee, respectively.

Bismuth trichloride - A clean, green catalyst for the synthesis of Hantzsch 1,4-dihydropyridines (DHPs)

Hantzsch 1,4-dihydropyridines (DHPs) are synthesized in good to excellent yields from aldehydes, 1,3-dicarbonyl compounds and ammonium acetate using bismuth trichloride which acts as mild Lewis acid promoter and 10 mol% is enough for this protocol under solvent free conditions.

β-Iodoallenolates as Springboards for Annulation Reactions

Beta-iodoallenolates II, generated from alkynones I with tetra-n-butylammonium iodide and a Lewis acid, underwent selective single or double annulation, depending on the Lewis acid promoter. Treatment with TiCl(4) gave cyclohexenyl alcohols III, whereas BF(3) x OEt(2) gave oxadecalins IV. The scope and limitations of the two annulation reactions are described.

Concise Synthesis of a Pentasaccharide Related to the Anti-Leishmanial Triterpenoid Saponin Isolated from Maesa balansae

Concise synthesis of the glycone part (a pentasaccharide) of the anti-leishmanial triterpenoid saponin isolated from Maesa balansae is reported. A late-stage TEMPO-mediated oxidation of a primary hydroxyl group to carboxylic acid has been achieved under phase-transfer conditions. Glycosylations were performed either by thioglycoside or glycosyl trichloroacetimidate activation using sulfuric acid immobilized on silica (H2SO4-silica) in conjunction with N-iodosuccinimide and alone, respectively. H2SO4-silica was proved to be a better choice as promoter than conventional Lewis acid promoters such as TfOH or TMSOTf.

Chiral N-phosphonyl imine chemistry: asymmetric additions of ester enolates for the synthesis of beta-amino acids.

Chiral phosphonyl imines attached by 1-naphthyl protection group were found to react with lithium ester enolates smoothly and give chiral beta-amino esters in good yields (70-88%) and up to excellent diastereoselectivity (>99:1 dr). Triisopropoxytitanium (IV) chloride was found to enhance diastereoseletivity when used as the Lewis acid promoter. The chiral auxiliary can be readily removed by treating with HBr to give free amino esters. The absolute structure has been unambiguously determined by converting one of the products into an authentic sample. This reaction provides an easy access to beta-amino acid derivatives.

Efficient Transformation of Azides to Primary Amines Using the Mild and Easily Accessible CeCl3·7H2O/NaI System

Because of the nitrogen functionality, the azido group plays an important role in the synthesis of amines, and numerous reduction methods of azides to primary amines are reported. Recent reports have highlighted the capability of NaI as a useful reagent for this transformation when it is used in combination with a Lewis acid promoter. However, these methods often suffer from harsh reaction conditions; for this reason, the development of a simple and efficient protocol using NaI in presence of inexpensive and readily available cerium salts Lewis acids would extend the scope of this organic transformation. In continuation of our interest on the use of the CeCl3.7H2O/NaI system, in this paper we report how azides undergo reduction by NaI in the presence of CeCl3.7H2O in refluxing acetonitrile under neutral conditions to produce the corresponding primary amines. The rate and yield of the reaction are considerably improved by employing this microwave-assisted procedure, and this may be of value for the preparation of densely functionalized molecules having biological and pharmaceutical activities.

Fe 2(SO 4) 3· xH 2O-catalyzed per- O-acetylation of sugars compatible with acid-labile protecting groups adopted in carbohydrate chemistry

Fully acetylated saccharides are inexpensive and very useful starting materials for the synthesis of many naturally occurring glycosides, oligosaccharides, and glycoconjugates. Ferric sulfate hydrate (Fe 2(SO 4) 3· xH 2O) was found to be a valuable Lewis acid promoter in the per- O-acetylation reaction of saccharides with acetic anhydride in 100% of conversion rate and 88–99% yields. Interestingly, the procedure is perfectly compatible with the presence of a variety of acid-labile protecting groups, such as isopropylidene, benzylidene, trityl, and TBDMS groups. The reactions were simply performed by stirring the mixture of a sugar with a slight excessive acetic anhydride in the presence of 2.0 mol % of Fe 2(SO 4) 3· xH 2O at rt and the pure products were obtained by a simple dilution of the reaction mixture with dichloromethane and washings with aqueous Na 2CO 3.

Synthesis of enantiomerically enriched (R)-5-tert-butylazepan-2-one using a hydroxyalkyl azide mediated ring-expansion reaction

A procedure for the conversion of a symmetrical ketone to an enantiomerically pure lactam is described. The technique described here involves a ring-expansion reaction of a 4-substituted cyclohexanone accomplished with a chiral 1,3-azidopropanol derivative. The procedure entails first a one-step preparation of (R)-1-phenyl-3-azidopropanol from a commercially available halide precursor, which is then reacted with the ketone using BF(3) x OEt(2) as a Lewis acid promoter. The resulting lactam is subsequently converted into a chiral lactam of high enantiopurity via the two-stage removal of the chiral nitrogen substituent. The present protocol carries out the diastereoselective ring-expansion reaction with higher selectivity than competing processes and is generally useful for the preparation of 5-substituted caprolactams.