Synthesis of BINOL derived phosphorodithioic acids as new chiral Brønsted acids and an improved synthesis of 3,3′-disubstituted H8-BINOL derivatives

Original phosphorodithioic acid diesters were prepared according to an improved synthesis of 3,3′-disubstituted H₈-BINOL derivatives. In preliminary experiments, these new Brønsted acids were tested as organocatalysts in three reactions. They promoted the Nazarov cyclisation with mixed selectivities, the Mannich reaction with good enantioselectivity and they catalyzed efficiently the alkylation of N-acyliminium with enol silyl ether.     

A convenient protocol for the synthesis of axially chiral Brønsted acids

Partially hydrogenated binaphthol monophosphoric acids were prepared via an improved four-step sequence. It is demonstrated that typical protection and deprotection of the phenolic groups are dispensable. The vinyl-substituted derivative has been polymerized to give a novel polymerized organocatalyst.     

Facile evolution of asymmetric organocatalysts in water assisted by surfactant Brønsted acids

Simple mixing of chiral amines and surfactant Brønsted acids such as p-dodecyl benzenesulfonic acid (DBSA) leads to highly effective and selective organocatalysts in water. The in situ generated catalysts catalyze highly stereoselective desymmetrization of prochiral ketones via direct aldol reactions (up to >16:1 dr, >99% ee) in water using micelle as reaction media. The current strategy was also applied in asymmetric Michael addition leading to a catalytic system with good activity and stereoselectivity.     

Palladium-catalyzed asymmetric hydrogenation of simple ketones activated by Brønsted acids

Homogeneous Pd(OCOCF₃)₂/(R)-C₄-TunePhos has been successfully applied in the asymmetric hydrogenation of simple ketones activated by catalytic amount of Brønsted acid with up to 88% ee.     

Electrochemical fluorination (Simons process) – A powerful tool for the preparation of new conducting salts, ionic liquids and strong Brønsted acids

Electrochemical fluorination (Simons process) provides a cheap commercial access to a series of tris(perfluoroalkyl)diflurophosphoranes. These substances are convenient starting material for the preparation of various fluoro-chemicals. The synthesis of new conducting salts and ionic liquids with perfluoroalkyl-fluorophosphate (FAP) and perfluoroalkyl-phosphinate anions is described. FAP ionic liquids exhibit excellent hydrolytic stability, low viscosity and high electrochemical and thermal stability. Organic and inorganic salts with FAP anions possess high electrochemical stability and conductivity that makes them attractive for application in several electrochemical devices (Li-ion batteries, super-capacitors, etc.). The possible application of H[(R_F)₃PF₃] (HFAP), (R_F)₂P(O)(OH) and (R_F)P(O)(OH)₂ as components of proton-conducting membranes is discussed.     

Development of N,N-bis(perfluoroalkanesulfonyl)squaramides as new strong Brønsted acids and their application to organic reactions

New strong Brønsted acids derived from a squaric acid scaffold bearing different perfluoroalkanesulfonyl groups have been developed and applied to several organic reactions. These squaramides are bench-stable and exhibit much higher reactivities in several organic reactions than squaric acid itself. N,N-Bis(trifluoromethanesulfonyl)squaramide 2a was applied to the Mukaiyama aldol reaction and Mukaiyama Michael reaction. Mechanistic studies revealed that the Brønsted acid might be the predominant catalyst through direct protonation of carbonyl compound by the acid itself rather than the silylated Brønsted acid. The utility of this acid 2a was further extended to Hosomi-Sakurai allylation of aldehydes and a carbonyl-ene reaction. Furthermore, other squaramides 2b and c bearing longer perfluoroalkyl chains have been developed, which are also bench-stable and displayed similar reactivities with squaramide 2a in several organic reactions.     

Gold and Brønsted acid catalyzed isomerization of [3]cumulenols and [3]cumulenones: efficient syntheses of 1,5-dien-3-ynes and furan derivatives

An attractive method for assembling π-conjugated dienynes with high stereoselectivity was achieved by dehydration reaction of TMS-substituted [3]cumulenols catalyzed by TsOH·H₂O. On the other hand, cycloisomerizations of the corresponding [3]cumulenones catalyzed by gold(I) complexes afford vinyl furans through activation of the cumulenic double bond via a π-complex, and during the process, deprotonation from an alkyl group on cumulene terminus takes place to induce the isomerization.     

Asymmetric sp C-H functionalization via a chiral Brønsted acid-catalyzed redox reaction for the synthesis of cyclic aminals

An organocatalytic asymmetric tandem 1,5-hydride transfer/ring closing reaction of o-aminobenzoketones with anilines to give cyclic aminals in fairly good diastereo- and enantioselectivities.     

Synthesis of tetrahydroisoquinolines and isochromans via Pictet-Spengler reactions catalyzed by Brønsted acid-surfactant-combined catalyst in aqueous media

Perfluorooctanesulfonic acid (PFOSA), Brønsted acid-surfactant-combined catalyst, efficiently catalyzes the Pictet-Spengler reactions of β-arylethyl carbamate derivatives with aldehydes in water. The present reaction is accelerated by the addition of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP). PFOSA in HFIP-water (10 v/v %) is also successfully applied to the oxa-Pictet-Spengler reactions of β-arylethyl alcohol compounds.     

Brønsted acidity of ceric ammonium nitrate in anhydrous DMF. The role of salt and solvent in sucrose cleavage

The generation of an unexpected Brønsted acidity in anhydrous DMF at 50 °C was evidenced by NMR measurements during the investigation on the course of sucrose cleavage by ceric ammonium nitrate (CAN). The formation of a nitrooxy derivative of DMF by reaction with CAN is responsible for this acidity. The reactivity of CAN at 50 °C with several solvents was evaluated by voltammetric and potentiometric measurements. The possible release of protons from these reactions, particularly when aqueous solvent mixtures are used, should always be taken into account in the mechanistic interpretation of CAN synthetic applications.     

Chiral Brønsted acid-catalyzed hydrophosphonylation of imines—DFT study on the effect of substituents of phosphoric acid

The enantioselective hydrophosphonylation reaction of diisopropyl phosphite with aldimine furnished α-amino phosphonates with high enantioselectivities by means of a chiral phosphoric acid. DFT calculation of the effect of 3,3′-substituents of the phosphoric acid revealed the reason for the high enantioselectivities.     

Theory-guided design of Brønsted acid-assisted phosphine catalysis: synthesis of dihydropyrones from aldehydes and allenoates

The phosphine-catalyzed addition of 2,3-butadienoates to aldehydes has been extended to the formation of disubstituted dihydro-2-pyrones. The requisite shift in equilibrium of the intermediate zwitterionic β-phosphonium dienolates toward the s-cis intermediate was accomplished through the use of a Brønsted acid additive, which disrupts the favorable Coulombic interaction present in the s-trans intermediate. The detailed nature of the synergistic interactions involving the Brønsted acid additives and phosphine involved in the formation of s-cis β-phosphonium dienolates was analyzed through a series of DFT calculations. Unlike previously reported annulations of aldehydes with allenoates, where trialkylphosphines are optimal catalysts, in this study triphenylphosphine was also found for the first time to be a suitable catalyst for the synthesis of dihydropyrones. This method provides a one-step route toward functionalized dihydropyrones from simple, stable starting materials. In addition, new reaction pathways of phosphine-catalyzed allene annulations are unveiled, with the formation of dihydropyrones being the first example of dual activation in this sphere.     

Synthesis of furo[2,3-b]pyridin-4(7H)-ones and related quinolinone via Brønsted acid-promoted cyclisation of alkynes

N-Alkyl-4-alkoxy-3-alkynylpyridin-2(1H)-ones readily undergo acid-promoted 5-endo-heteroannulation to furopyridinium intermediates that are dealkylated in situ to provide the corresponding furo[2,3-b]pyridin-4(7H)-ones. The same strategy applies to the formation of furo[2,3-b]quinolin-4(9H)-ones. In the case of Me₃Si-substituted alkynes, hydration of the triple bond was observed.     

Solvent-free Brønsted acid catalysed alkylation of arenes and heteroarenes with benzylic alcohols

A simple and efficient alkylation of aromatic and heteroaromatic compounds via the direct S_N1-type nucleophilic substitution of benzylic alcohols in the presence of catalytic amounts of the strong Brønsted acid o-benzenedisulfonimide under neat conditions is herein reported. A library of di- and triaryl (and heteroaryl) methanes was prepared in good yields and high regioselectivity. The observed reactivity was shown to be in agreement with Mayr's nucleophilicity and electrophilicity scales.     

Brønsted acidic magnetic nano-Fe3O4-adorned calix[n]arene sulfonic acids: synthesis and application in the nucleophilic substitution of alcohols

Three magnetically recoverable Brønsted acidic calix[n]arene derivatives were successfully constructed by immobilizing calix[n]arene sulfonic acids onto silica-coated magnetic nanoparticles, a process, which allows calix[n]arene derivatives to acquire magnetic properties. All of the magnetically recoverable Brønsted acidic calix[n]arenes efficiently catalyze the coupling of electron-rich arenes with some alcohols in water. After separation and recovery from the reaction mixture by a simple magnet, these Brønsted acidic calix[n]arenes can be recycled many times without losing their catalytic activity.     

Highly efficient synthesis of N-confused meso-tetraspirocyclohexyl calix[4]pyrrole using Brønsted acidic ionic liquids as catalysts

An efficient, green and novel protocol is described for high yield synthesis of N-confused meso-tetraspirocyclohexyl calix[4]pyrrole. In aqueous solution, the condensation of pyrrole and cyclohexanone in the presence of Brønsted acidic ionic liquid catalysts afforded N-confused calix[4]pyrrole in up to 62.5% yield which represents a ∼threefold yield improvement over existing protocol and makes significant quantity of N-confused calix[4]pyrrole readily available.     

Iron/Brønsted Acid Catalyzed Asymmetric Hydrogenation: Mechanism and Selectivity‐Determining Interactions

Hydrogenation catalysts involving abundant base metals such as cobalt or iron are promising alternatives to precious metal systems. Despite rapid progress in this field, base metal catalysts do not yet achieve the activity and selectivity levels of their precious metal counterparts. Rational improvement of base metal complexes is facilitated by detailed knowledge about their mechanisms and selectivity‐determining factors. The mechanism for asymmetric imine hydrogenation with Knölker’s iron complex in the presence of chiral phosphoric acids is here investigated computationally at the DFT‐D level of theory, with models of up to 160 atoms. The resting state of the system is found to be an adduct between the iron complex and the deprotonated acid. Rate‐limiting H₂ splitting is followed by a stepwise hydrogenation mechanism, in which the phosphoric acid acts as the proton donor. C?H ??? O interactions between the phosphoric acid and the substrate are involved in the stereocontrol at the final hydride transfer step. Computed enantiomeric ratios show excellent agreement with experimental values, indicating that DFT‐D is able to correctly capture the selectivity‐determining interactions of this system.     

Synthesis of 1-C-alkyl-α-d-glucopyranosides by Lewis acid- or Brønsted acid-catalyzed O-glycosidation

We prepared several kinds of 1-C-alkyl-2,3,4,6-tetra-O-benzyl-α-d-glucopyranose derivatives containing methyl, ethyl, n-butyl, and benzyl groups as the alkyl groups at their anomeric positions. The Lewis acid- or Brønsted acid-catalyzed O-glycosidations using them as the glycosyl donors to synthesize 1-C-alkyl-d-glucopyranosides were investigated. Using 10 mol % of triphenylmethyl perchlorate efficiently catalyzed the glycosidation of 2,3,4,6-tetra-O-benzyl-1-C-methyl-α-d-glucopyranosyl dimethylphosphinothioate. The glycosidation using the 1-C-alkyl-2,3,4,6-tetra-O-benzyl-α-d-glucopyranosyl acetates smoothly proceeded in the presence of only 5 mol % of scandium(III) trifluoromethanesulfonate. The dehydration-condensation type glycosidation using the 1-C-alkyl-2,3,4,6-tetra-O-benzyl-α-d-glucopyranoses was significantly promoted using 5 mol % of bis(trifluoromethane)sulfonimide. These glycosidations successfully afforded various 1-C-alkyl-α-d-glucopyranosides in good yields with high α-stereoselectivities.     

Brønsted acid TfOH-mediated reactions of 2-(arylmethylene)cyclopropylcarbinols with acetonitrile

We report herein Brønsted acid TfOH-mediated reactions of 2-(arylmethylene)cyclopropylcarbinols with acetonitrile to give the corresponding ring-enlarged N-(3-arylmethylidenecyclobutyl)acetamides in moderate to good yields under mild conditions. A plausible mechanism is proposed on the basis of previous investigations.