Lewis acid-catalyzed reactions of mono-aryl group substituted methylenecyclopropanes with diethyl ketomalonate

Mono-aryl group substituted methylenecyclopropanes (MCPs) 1 react with diethyl ketomalonate 2a, an activated ketone, to give the corresponding 7-hydroxy-5-oxa-spiro[2,4]heptan-6-one derivatives 6 with syn-configuration in moderate yields in the presence of water under the catalysis of Lewis acids such as Sc(OTf)₃, Yb(OTf)₃ or In(OTf)₃ at room temperature. The reaction mechanism has been discussed on the basis of an ¹⁸O-labeling experiment.     

A mild procedure for the Lewis acid-catalyzed ring-opening of activated cyclopropanes with amine nucleophiles

The Lewis acid-catalyzed ring-opening of methyl 1-nitrocyclopropanecarboxylates with amine nucleophiles is described. The reaction proceeds at room temperature and with complete preservation of the enantiomeric purity from the electrophilic center of the cyclopropane to the acyclic product. The methodology was applied in an enantioselective synthesis of the dual serotonin/norepinephrine reuptake inhibitor (3R)-3-(1 H-indol-1-yl)- N-methyl-3-phenylpropan-1-amine.     

Lewis acid catalyzed ring-opening reactions of methylenecyclopropanes with diphenylphosphine oxide in the presence of sulfur or selenium

Methylenecyclopropanes undergo an interesting Lewis acid-catalyzed ring-opening reaction with diphenylphosphine oxide in the presence of sulfur or selenium upon heating at 85 degrees C in 1,2-dichloroethane to give the corresponding homoallylic thiol or selenol derivatives in good to high yields.     

Lewis acids catalyzed ring-opening reactions of methylenecyclopropanes and epoxides in supercritical carbon dioxide or modified supercritical carbon dioxide with perfluorocarbon

The reactions of methylenecyclopropanes (MCPs) and epoxides with alcohols and aromatic amines can be carried out in supercritical carbon dioxide (scCO₂) or modified scCO₂ with perfluorocarbon which offer a way to synthesize various alcohols, amino-alcohols, homoallylic ethers, and amines under an environmentally benign condition.     

Lewis acid-catalyzed novel [3+2] cycloaddition of methylenecyclopropanes with activated aldehydes or ketones

Methylenecyclopropanes react with activated aldehydes or ketones in the presence of various Lewis acids to give the corresponding [3+2] cycloaddition products having tetrahydrofuran (THF) skeleton in good yields and in some cases with high stereoselectivity.     

Lewis acid-catalyzed nucleophilic ring-opening/intramolecular Conia-ene reactions of methylenecyclopropane 1,1-diesters with propargyl alcohols

We presented a Lewis acid-catalyzed nucleophilic ring opening of methylenecyclopropane (MCP) 1,1-diesters with propargyl alcohols. Unlike the proximal-bond cleavage mode observed in cases of unactivated MCPs, the intrinsic characteristic of MCP 1,1-diesters gave a regiospecific distal-bond cleavage under attack of propargyl alcohols as nucleophiles. By combining a subsequent intramolecular Conia-ene reaction, 3,5-dimethylenetetrahydropyrans could be obtained in either a stepwise or a one-pot strategy.     

Rhodium-catalyzed ring-opening reactions of N-boc-azabenzonorbornadienes with amine nucleophiles

In the presence of a rhodium catalyst (5 mol %) generated in situ from [Rh(cod)Cl](2) and (S,S')-(R,R')-C(2)-ferriphos (4a), the asymmetric ring-opening reaction of azabenzonorbornadienes (1a-m) with various aliphatic and aromatic amines (2a-l) proceeded with high enantioselectivity (up to >99% ee) to give the corresponding 1,2-diamine derivatives 3 in high yields. In the specific case of pyrrolidine as nucleophile, Et(3)NHCl was necessary as an additive for good reactivity and enantioselectivity. Additionally, a practical protocol was developed for the ring-opening of 1a with volatile amines at elevated temperatures and standard pressure, using R(2)NH(2)I and i-Pr(2)NEt. The experimental results showed that the nature of the chiral ligand has the significant impact on the reactivity of the catalyst and the use of excess amount (2.2 eq to Rh) of the chiral ligand plays an important role to improve the enantioselectivity in the present asymmetric reaction.     

Lewis acid-catalyzed reactions on polystyrene

The action of aluminium halides upon polystyrene was studied as a function of the nature of the reaction medium and of the concentration of catalyst. It was demonstrated that polystyrene undergoes crosslinking, the extent of which is particularly important in chlorinated aliphatic solvents and at high catalyst concentrations. In additions, phenyl rings of the polymer are alkylated and halogenated by the solvent or catalyst. Infrared spectroscopic investigation of the structure of the products indicated that in most cases crosslinking was connected with the formation of 1,4-disubstituted, and eventually 1,2,4-trisubstituted benzenes. In carbon tetrachloride medium, meta substitution was also detected. In products obtained when polystyrene was treated with high amounts of the Lewis acid in CCl₄ medium degrees of substitution even higher than three were probable.     

Development of fluorous Lewis acid-catalyzed reactions

Organic synthetic methodology in the 21st century aims to conform to the principles of green sustainable chemistry (GSC) and we may expect that in the future, the realization of GSC will be an important objective for chemical industries. An important aim of synthetic organic chemistry is to implement waste-free and environmentally-benign industrial processes using Lewis acids as versatile as aluminum chloride. A key technological objective of our work in this area has been to achieve a "catalyst recycling system that utilizes the high activity and structural features of fluorous Lewis acid catalysts". Thus, we have developed a series of novel fluorous Lewis acid catalysts, namely the ytterbium(III), scandium(III), tin(IV) or hafnium(IV) bis(perfluoroalkanesulfonyl)amides or tris(perfluoro- alkanesulfonyl)methides. Our catalysts are recyclable and effective for acylations of alcohols and aromatics, Baeyer-Villiger reactions, direct esterifications and transesterifications in a fluorous biphasic system (FBS), in supercritical carbon dioxide and on fluorous silica gel supports.     

Lewis acid-catalyzed Mannich type reactions with potassium organotrifluoroborates

Three-component Lewis acid-catalyzed Mannich type reactions using potassium organotrifluoroborates (aryl, vinyl, and allyl reagents) has been developed as an extension of the standard Petasis reaction.     

Chiral Lewis acid-catalyzed asymmetric Baylis-Hillman reactions

An effective chiral Lewis acid-catalyzed asymmetric Baylis-Hillman reaction is described. Good to high enantioselectivities were obtained using 3 mol % chiral catalyst. Novel camphor-derived dimerized ligands were prepared from the condensation of (+)-ketopinic acid with the corresponding diamines and hydrazine under acidic conditions. When alpha-naphthyl acrylate was used as a Michael acceptor, the reaction is complete within 20 min with high stereoselectivity and in reasonable chemical yields.     

Acid-catalyzed intramolecular ring-opening reactions of cyclopropanated oxabenzonorbornadienes with alcohol nucleophiles

An investigation of intramolecular ring-opening reactions of various cyclopropanated oxabenzonorbornadienes (CPOBDs) with alcohol nucleophiles is reported, which forms two regioisomeric products in good yields. The effect of various tether lengths was explored, wherein increasing the alcohol tether length to 4 or 5 carbons exclusively generated Type 3 products in good yield, while C-1-hydroxymethyl substituted CPOBD formed a 1,3,5-cycloheptatriene derivative in excellent yield. Electron donating arene and electron withdrawing C-5-bridgehead substituents formed Type 3 major products, whereas electron withdrawing arenes and electron donating C-5 substituents preferentially afforded Type 2 compounds. A mechanism is also proposed for the formation of both regioisomeric products.     

Lewis acid-catalyzed reactions of donor-acceptor cyclopropanes with furan derivatives

Lewis acid-catalyzed reactions of dialkyl 2-arylcyclopropane-1,1-dicarboxylates with 2,5-dimethylfuran were found to give products of [3+2]-cycloaddition to C(2)-C(3) bond, which contain reactive vinyl ether moiety. These adducts can be further transformed into various products depending on the Lewis acid, the nucleophilicity of aryl group in starting cyclopropane and the ratio of reagents. The vinyl ether moiety can attack the appropriate nucleophilic center in intramolecular or intermolecular mode or can undergo cycloaddition to the second equivalent of donor-acceptor cyclopropane. Alternatively, 2,5-diphenylfuran formed Friedel-Crafts products only when reacted with donor-acceptor cyclopropanes.     

Iridium-catalyzed asymmetric ring-opening reactions of N-Boc-azabenzonorbornadiene with secondary amine nucleophiles

Iridium-catalyzed asymmetric ring-opening reactions of N-Boc-azabenzonorbornadiene with a number of secondary amines has been developed for the first time. The reaction gave 1,2-trans-diamine derivatives in moderate to good yields with high enantioselectivity in the presence of 2.5 mol % of [Ir(COD)Cl]2 and 5 mol % of (S)-BINAP. The trans-configuration of the 1,2-diamino products was confirmed by X-ray crystallography.     

Iridium-catalyzed ring-opening reactions of unsymmetrical oxabenzonorbornadienes with water and alcohol nucleophiles

The iridium-catalyzed ring-opening reaction of unsymmetrical oxabenzonorbornadienes (OBD) with water and alcohol nucleophiles is reported, with the effects of various C₁-substituents explored. Electron-donating alkyl groups lead entirely to the substituted naphthol derivatives in excellent yields while substitution of the C₁ position for electron-withdrawing groups afforded ring-opened products in fair to excellent yields with excellent regioselectivity. The reaction was demonstrated to be highly regioselective for the C₂ position with no C₃ regioisomer observed in all cases. A proposed mechanism for the formation of C₂ regioisomeric ring-opened products has been included.     

Lewis acid-catalyzed Prins-type reactions of methylenecyclopropylcarbinols with aldehydes and aldimines

Lewis acid-catalyzed Prins-type reactions of methylenecyclopropylcarbinols with aldehydes and aldimines proceeded smoothly to give the corresponding 3-oxa-bicyclo[3.1.0]hexane units via 5-exo cyclization in good to high total yields.     

Lewis acid-catalyzed tri- and difluoromethylation reactions of aldehydes

The first Lewis acid-catalyzed trifluoromethylation reactions of aldehydes with Me3SiCF3 under TiF4/DMF, Ti(O iPr)4/DMF and Cu(OAc)2/dppp/toluene conditions are described. We have successfully applied this methodology to the difluoromethylation of aldehydes using Me3SiCF2SePh, Me3SiCF2P(O)OEt2 and Me3SiCF2SPh.     

Ti-catalyzed ring-opening oxidative amination of methylenecyclopropanes with diazenes

The ring-opening oxidative amination of methylenecyclopropanes (MCPs) with diazenes catalyzed by py₃TiCl₂(NR) complexes is reported. This reaction selectively generates branched α-methylene imines as opposed to linear α,β-unsaturated imines, which are difficult to access via other methods. Products can be isolated as the imine or hydrolyzed to the corresponding ketone in good yields. Mechanistic investigation via density functional theory suggests that the regioselectivity of these products results from a Curtin–Hammett kinetic scenario, where reversible β-carbon elimination of a spirocyclic [2 + 2] azatitanacyclobutene intermediate is followed by selectivity-determining β-hydrogen elimination of the resulting metallacycle. Further functionalizations of these branched α-methylene imine products are explored, demonstrating their utility as building blocks.

The ring-opening oxidative amination of methylenecyclopropanes (MCPs) with diazenes catalyzed by py₃TiCl₂(NR) complexes is reported.     

Lewis acid-catalyzed cascade reactions of arylmethylenecyclopropanes with 1,1,3-triarylprop-2-yn-1-ols or their methyl ethers

Arylmethylenecyclopropanes 1 can react with 3-methoxy-1,3,3-triarylprop-1-yne 2 or 1,1,3-triarylprop-2-yn-1-ol 2-OH to give the corresponding functionalized methylenecyclobutene, cyclobutane, and cyclopropane derivatives in the presence of Lewis acid BF3.OEt2 under mild conditions. A plausible Meyer-Schuster rearrangement mechanism has been proposed.     

Brønsted acid-mediated ring-opening reactions of methylenecyclopropanes: a dramatic counter ion effect

We report herein two different ring-opening patterns of methylenecyclopropanes (MCPs) in the presence of two Brønsted acids heptadecafluorooctane-1-sulfonic acid (C₈F₁₇SO₃H) and toluene p-sulfonic acid (TsOH) under mild conditions: (a) the ring-opening of MCPs by H₂O and subsequent etherification give the corresponding homoallylic ethers in the presence of heptadecafluorooctane-1-sulfonic acid; (b) the direct ring-opening of MCPs by the Brønsted acid gives the corresponding homoallylic alcohol derivatives in the presence of toluene p-sulfonic acid.