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The development of sustainable, functional-group-tolerant catalysis is highly significant from the perspectives of safety, user-friendliness, and cost-effectiveness. We report herein the triple hydrogen-bonding donor activator N -triflyl phosphoric triamide (N -TPT ) for the synergistic Brønsted acid aquacatalysis of multicomponent allylation 'on-water'. The reaction demonstrated remarkable efficiency in converting polar diol substrate, such as 1,3-dihydroxyacetone, into α-tertiary amine derivative incorporating homoallylic amine functionalities using bulk water as the reaction medium. The single crystal X-ray structure and control experiments highlighted the crucial role of multiple hydrogen bonds in enabling this aqueous reaction. [ABSTRACT FROM AUTHOR]

This article presents a new method for synthesizing α-quaternary carbaldehydes through the chemoselective House-Meinwald rearrangement of trisubstituted epoxides. The authors used Brønsted acids as catalysts and identified optimal reaction conditions. The method allows for the synthesis of various carbaldehydes and has been validated for stereospecific reactions. The authors suggest that this method could be useful in the total synthesis of natural products. [Extracted from the article]

We report a Brønsted acid‐catalyzed synthesis of tetrasubstituted allenyl compounds decorated with heterocyclic sulfenyl group. The reaction proceeds readily from available propargylic alcohols in the presence of pentacarboxycyclopenatadienes (PCCPs) as organocatalysts. The developed strategy provides tetrasubstituted allene derivatives in high yields (from 55 to 98 %) and under mild reaction conditions. [ABSTRACT FROM AUTHOR]

Over the last ten years, the combination of organocatalysis with transition metal (TM) catalysis has become one of the most important toolboxes used for synthesizing optically pure compounds containing chiral quaternary centers, including spiro heterocyclic molecules. The dominant method in the enantioselective synthesis of spiro heterocyclic compounds based on synergistic catalysis includes chiral aminocatalysis and NHC catalysis, as already established covalent organocatalytic strategies. Another area of organocatalysis widely combined with TM catalysis producing enantiomerically enriched spiro heterocyclic compounds is non‐covalent catalysis, dominated by chiral phosphoric acids, thiourea, and squaramide derivatives. This review article aims to summarize enantioselective methods used for constructing spirocyclic heterocycles based on a combination of organocatalysis and transition metal catalysis. [ABSTRACT FROM AUTHOR]

This review is devoted to underpinning the contributions of Indian researchers towards asymmetric organocatalysis. More specifically, a comprehensive compilation of reactions mediated by a wide range of non-covalent catalysis is illustrated. A detailed overview of vividly catalogued asymmetric organic transformations promoted by hydrogen bonding and Brønsted acid catalysis, alongside an assortment of catalysts is provided. Although asymmetric organocatalysis has etched itself in history, we aim to showcase the scientific metamorphosis of Indian research from baby steps to large strides within this field. 1 Introduction 2 Non-Covalent Catalysis and Its Various Activation Modes 3 Hydrogen-Bonding Catalysis 3.1 Urea- and Thiourea-Derived Organocatalysts 3.1.1 Thiourea-Derived Organocatalysts 3.1.2 Urea-Derived Organocatalysts 3.2 Squaramide-Derived Organocatalysts 3.2.1 Michael Reactions 3.2.2 C-Alkylation Reactions 3.2.3 Mannich Reactions 3.2.4 [3+2] Cycloaddition Reactions 3.3 Cinchona-Alkaloid-Derived Organocatalysts 3.3.1 Michael Reactions 3.3.2 Aldol Reactions 3.3.3 Friedel–Crafts Reactions 3.3.4 Vinylogous Alkylation of 4-Methylcoumarins 3.3.5 C-Sulfenylation Reactions 3.3.6 Peroxyhemiacetalisation of Isochromans 3.3.7 Diels–Alder Reactions 3.3.8 Cycloaddition Reactions 3.3.9 Morita–Baylis–Hilman Reactions 4 Brønsted Acid Derived Organocatalysts 4.1 Chiral Phosphoric Acid Catalysis 4.1.1 Diels–Alder Reactions 4.1.2 Addition of Ketimines 4.1.3 Annulation of Acyclic Enecarbamates 5 Conclusion [ABSTRACT FROM AUTHOR]

Since the innovative work of Terada and Akiyama, asymmetric reaction using chiral Brønsted acid has attracted great attention. Asymmetric aldol reactions are extensively studied in different organocatalysis. Brønsted acid-catalyzed aldol reaction may be carried out directly without modification of the substrates or Mukaiyama type aldol reaction using silyl enol ether as nucleophiles. The reaction may proceed through the formation of enol intermediate followed by the attack to the electrophile while Mukaiyama type aldol reactions may follow two mechanistic pathways-Brønsted acidic pathways where Brønsted acid directly activates the substrate or Lewis acid pathways where Brønsted acid acts as precatalyst. Here, the recent advancement of asymmetric aldol reactions using chiral Brønsted acid as a catalyst and the fate of the catalysts in the reaction has been discussed in this review. It is observed that some kinds of aldol reactions have rarely been studied and need more attention. [ABSTRACT FROM AUTHOR]

Here we present an enantioselective aminalization of aldehydes catalyzed by Brønsted acids based on pentacarboxycyclopentadienes (PCCPs). The cyclization reaction using readily available anthranilamides as building blocks provides access to valuable 2,3-dihydroquinazolinones containing one stereogenic carbon center with good enantioselectivity (ee up to 80%) and excellent yields (up to 97%).

The Morita‐Baylis‐Hillman (MBH) reaction has been stablished as an important C−C bond‐forming transformation between carbonyl‐containing compounds and activated olefins. However, the slow reaction rate usually observed with electron‐rich electrophilic partners hinders a more widespread use of this reaction. In order to overcome this drawback, the effects of several Brønsted acids on the rate of DABCO‐catalyzed MBH reactions were evaluated. The protocol is operationally simple, involving neat and open‐flask conditions, and is compatible with a wide range of reagents. We suggest a general acid catalysis mechanism to be responsible for the rate increase. The synthetic versatility of the MBH adducts is exemplified with a two‐steps diastereoselective synthesis of the natural product (±)‐sitophilure. We hope this acid‐mediated protocol to have potential use as a general methodology for the MBH reaction. [ABSTRACT FROM AUTHOR]

A dearomative spirocyclization of diazo‐functionalized indoles was developed under metal‐free conditions. Although the spiroindolenine architecture with a tertiary alkyl substituent at the 2‐position is a privileged scaffold of bioactive molecules, a general synthetic strategy has remained elusive. In this study, a dual catalyst system comprising maleic acid and Schreiner's thiourea was used to construct a spiroindolenine core that was inaccessible by rhodium or silver catalysis. Computational studies revealed a unique macrocyclic transition state consisting of the substrate, maleic acid, and thiourea cocatalyst, which lowered the activation energy of spirocyclization through multipoint mutual interactions. [ABSTRACT FROM AUTHOR]

The mechanism of Brønsted acid‐initiated formal [1,3]‐rearrangement was rationalized using density functional theory (DFT) calculations. The computed mechanism comprises I) fragmentation: (a) imino‐nitrogen protonation, (b) proton transfer to olefin, (c) 1,2‐shift, and (d) C−C bond cleavage, and II) product formation: (e) methylene addition, (f) azonia‐[3,3]‐sigmatropic rearrangement, and (g) methylene elimination. The ene‐aldimine fragmentation to the 2‐azaallenium cation was found to be a highly reactive intermediate and the real catalyst species. The stereoselectivity for asymmetric formal [1,3]‐rearrangement of optically pure ene‐aldimine is in good agreement with chair transition state of azonia‐[3,3]‐sigmatropic rearrangement step and is supported by DFT calculation. Our computational study provides important mechanistic insights for ene‐aldimine rearrangements and guides the design of chiral catalysts for rearrangement process. [ABSTRACT FROM AUTHOR]

An enantioselective intermolecular addition reaction of azlactones, as carbon nucleophiles, with styrene derivatives, as simple olefins, was demonstrated using a newly developed chiral Brønsted acid catalyst, namely, F10BINOL‐derived N‐triflyl phosphoramide. Addition products having vicinal tetrasubstituted carbon centers, one of which is an all‐carbon quaternary stereogenic center, were formed in good yields with moderate to high stereoselectivities. Extremely high acidity of the new chiral Brønsted acid was confirmed by its calculated pKa value based on DFT studies and is the key to accomplishing not only high catalytic activity but also efficient stereocontrol in the intermolecular addition. [ABSTRACT FROM AUTHOR]

The enantioselective, catalytic vicinal difluorination of alkenes is reported by II/IIII catalysis using a novel, C2‐symmetric resorcinol derivative. Catalyst turnover via in situ generation of an ArIIIIF2 species is enabled by Selectfluor oxidation and addition of an inexpensive HF–amine complex. The HF:amine ratio employed in this process provides a handle for regioselective orthogonality as a function of Brønsted acidity. Selectivity reversal from the 1,1‐difluorination pathway (geminal) to the desired 1,2‐difluorination (vicinal) is disclosed (>20:1 in both directions). Validation with electron deficient styrenes facilitates generation of chiral bioisosteres of the venerable CF3 unit that is pervasive in drug discovery (20 examples, up to 94:06 e.r.). An achiral variant of the reaction is also presented using p‐TolI (up to >95 % yield). AC2‐symmetric resorcinol derivative was used in the enantioselective, catalytic vicinal difluorination of alkenes by II/IIII catalysis. The HF:amine ratio employed in this process provides a handle for regioselective orthogonality as a function of Brønsted acidity. Selectivity reversal from the 1,1‐difluorination pathway (geminal) to the desired 1,2‐difluorination (vicinal) is disclosed. [ABSTRACT FROM AUTHOR]

The first example of solvent-free, organocatalyzed, polymerization of 1,3-dioxolan-4-ones, used as easily accessible monomers for the synthesis of polylactic acid (PLA), is described here. An optimization of reaction conditions was carried out, with p-toluensulfonic acid emerging as the most efficient Brønsted acid catalyst. The reactivity of the monomers in the tested conditions was studied following the monomer conversion by 1H NMR and the molecular weight growth by SEC analysis. A double activation polymerization mechanism was proposed, pointing out the key role of the acid catalyst. The formation of acetal bridges was demonstrated, to different extents depending on the nature of the aldehyde or ketone employed for lactic acid protection. The polymer shows complete retention of stereochemistry, as well as good thermal properties and good polydispersity, albeit modest molecular weight.

Abstract: The present study reports the organocatalytic enantioselective allylic amination of Morita–Baylis–Hillman carbamates efficiently catalyzed by a chiral amine in the presence of a Brønsted acid. Chiral allylic amines were produced in high yields (up to 98 %) and enantioselectivities (up to 97 % ee). This method provides an efficient and easily performed route to prepare α‐methylene‐β‐lactams, and other optically active β‐lactams, such as the cholesterol‐lowering drug Ezetimibe. [ABSTRACT FROM AUTHOR]

Chiral imidodiphosphoric acids were employed as catalysts for the enantioselective α -chlorination of β -keto esters and amides using NCS as the chlorine source, providing a series of optically active products with good to high enantioselectivities (74–95% ee) and excellent yields (92–99%). This represents the first report of the Brønsted acid catalyzed enantioselective α -chlorination of cyclic β -keto derivatives. [ABSTRACT FROM AUTHOR]

Abstract: Reported is the first organocatalytic asymmetric 1,3‐alkyl shift in alkyl aryl ethers for the synthesis of chiral 3,3′‐diaryloxindoles using a chiral Brønsted acid catalyst. Preliminary results showed that each enantiomer of the 3,3′‐diaryloxindole, and a racemic mixture, showed different antiproliferative activities against HeLa cell lines by using an MTT assay. [ABSTRACT FROM AUTHOR]

A new Lewis acid-catalyzed endo-selective Prins bicyclization of γ,δ-unsaturated aldehydes or ketones with a broad range of aldehydes to dioxabicyclo[2.2.2]octanes is disclosed. When using a chiral BINOL-derived N-triflylphosphoramide (NTPA) as catalyst and glyoxylate esters as substrates, the cross-dimerization afford functionalized bicyclic acetals with excellent diastereo- and enantioselectivities. [ABSTRACT FROM AUTHOR]

The first Brønsted acid catalyzed enantioselective addition of thiols to the in situ generated ortho-quinone methides (o-QMs) is described. Complementary to the chiral amine catalyzed approach, the present reaction employs a chiral phosphoric acid as the catalyst. The readily available o-hydroxybenzyl alcohols serve as the atom-economical precursors of o-QMs to react with tritylthiol with moderate to good efficiency and enantioselectivity under mild conditions. [ABSTRACT FROM AUTHOR]

H-bonding organocatalysis using (thio)urea/amine achieved massive success. H-bonding binding with Brønsted acid catalysis, especially in polymerizations, was scarcely explored. Here we disclosed 1,3- bis -(3,5- bis (trifluoromethyl)phenyl)thiourea (TU) as hydrogen bond donor (HBD), combined with trifluoroacetic acid (TFA) as a Brønsted acid (BA), promoted efficient controlled/living ring-opening polymerization (ROP) of δ-valerolactone (δ-VL) and ε-caprolactone (ε-CL) at room temperature. The ROPs of δ-VL and ε-CL with benzyl alcohol (BnOH) as the initiator yielded poly(δ-valerolactone) (PVL, M n, NMR = 1900–9900 g mol −1 , M w / M n = 1.28–1.34) and poly(ε-caprolactone) (PCL, M n, NMR = 2400–11,600 g mol −1 , M w / M n = 1.19–1.35) with predicted molecular weights and narrow dispersities. A plausible mechanism of the ROP promoted by associations of TU with TFA through double hydrogen bonding was suggested, in which stabilizing of the carboxylate anion and enhancing of the Brønsted acidity made the catalytic ROPs by TU–TFA viable. The quantitative incorporation of the initiator into the polymer chains was demonstrated by 1 H NMR and MALDI-ToF MS measurements. The controlled/living fashion of the polymerization was supported by the kinetics and chain extension experiments. Synthesis of well defined block copolymers of PVL- b -PCL and PCL- b -PVL verified again the ROPs were in controlled/living manner, and suggested the hydrogen bond donor binding with Brønsted acid catalysis to be a generally applicable method. [ABSTRACT FROM AUTHOR]

The asymmetric synthesis of tetrahydropyridines employing a normal electron-demanding aza-Diels-Alder reaction has been developed. The [4+2] cycloaddition of ethyl glyoxylate imine with aryl-substituted 2-silyloxy-1,3-butadienes is catalyzed by 5 mol% of a BINOL-derived phosphoric acid and in general leads to good yields and ee values with good to excellent diastereoselectivities. The cycloadducts can be further converted into the corresponding piperidinones, which are important pipecolic acid derivatives. [ABSTRACT FROM AUTHOR]

Allylation, trans- and cis-crotylation of (2 E,4 E)-2,4-dimethylhexadienal, a representative α,β,γ,δ-unsaturated aldehyde, was carried out under different catalytic and stoichiometric conditions. The reactions catalyzed by organocatalysts TRIP-PA and N, N′-dioxides gave the best results with respect to yields, asymmetric induction, and catalyst load in comparison to other procedures. The developed methodology was applied in the enantioselective synthesis of (5 R,6 S)-(+)-pteroenone, a defensive metabolite (ichthyodeterrent) of the Antarctic pteropod Clione antarctica. [ABSTRACT FROM AUTHOR]

A convergent, organocatalytic asymmetric aminomethylation of α,β-unsaturated aldehydes by N-heterocyclic carbene (NHC) and (in situ generated) Brønsted acid cooperative catalysis is disclosed. The catalytically generated conjugated acid from the base plays dual roles in promoting the formation of azolium enolate intermediate, formaldehyde-derived iminium ion (as an electrophilic reactant), and methanol (as a nucleophilic reactant). This redox-neutral strategy is suitable for the scalable synthesis of enantiomerically enriched β2-amino acids bearing various substituents. [ABSTRACT FROM AUTHOR]

Highly diastereo- and enantioselective conjugate addition of 3-aryloxindoles to maleimide was accomplished under base-free phase-transfer conditions. The effect of Brønsted acid co-catalyst was examined, and we found that the use of a phenol derivative as co-catalyst was effective for obtaining the target conjugate adduct in good yield with high stereoselectivity. [ABSTRACT FROM AUTHOR]

A highly diastereoselective synthesis of 4-amidotetrahydropyran derivatives has been achieved using a catalytic amount ofo-benzenedisulfonimide under mild conditions involving sequential allylation and Prins–Ritter amidation. The oxo-carbenium ion formed in Prins cyclization could be successfully trapped with nitriles through Ritter amidation. The catalyst is highly efficient in promoting both allylation and Prins cyclization with a net addition of nitrile. The catalyst can be easily recovered and reused in subsequent reactions. [ABSTRACT FROM AUTHOR]

Nitrogen-containing chiral heterocycles represent important structural elements with wide occurrence in natural and unnatural compounds exhibiting important biological activities. Herein, we describe our recent endeavors directed toward the Brønsted acid-catalyzed 1,3-dipolar cycloaddition and alkylation reactions, together with the metal/Brønsted acid relay catalytic cascade reactions to access some typical nitrogenous heterocyclic structures and natural alkaloids, including (+)-folicanthine and (+)-gliocladin C. [ABSTRACT FROM AUTHOR]

Abstract: Brønsted acid catalyzed azlactone ring opening in the presence of different nucleophiles leading to the efficient synthesis of protected amides and amino esters is presented. Sixteen compounds were synthesized in good to excellent isolated yields. Mechanism investigation by using ESI(+)-MS/MS revealed that the CSA catalyst promotes azlactone activation for electrophilic attack facilitating therefore the attack of the nucleophile that leads to ring opening and protonation. [Copyright &y& Elsevier]

Caught in the act: A new concept for asymmetric Brønsted acid catalysis is presented. Compounds containing an acidic functionality in addition to an anion recognition site act as powerful conjugate‐base‐stabilized Brønsted acid catalysts. This strategy was applied to the first catalytic enantioselective three‐component Povarov reaction of indoline and other secondary aromatic amines (see scheme; M.S.=molecular sieves). [ABSTRACT FROM AUTHOR]

Brønsted acid, C-C bond formation, Morita-Baylis-Hillman, Organocatalysis, Sustainable chemistry Keywords: Brønsted acid; C-C bond formation; Morita-Baylis-Hillman; Organocatalysis; Sustainable chemistry EN Brønsted acid C-C bond formation Morita-Baylis-Hillman Organocatalysis Sustainable chemistry 1 1 1 03/11/22 20220307 NES 220307 B The Cover Feature b illustrates the effect of acetic acid on the rate of the Morita-Baylis-Hillman reaction. Cover Feature: An Improved Protocol for the Morita-Baylis-Hillman Reaction Allows Unprecedented Broad Synthetic Scope (Eur. J. Org. [Extracted from the article]

Abstract: The first asymmetric reduction of ketimines with catecholborane employing an enantiopure N-triflyl phosphoramide as the organocatalyst has been developed. Five mole% of the catalyst provides the corresponding secondary amines in very good to almost quantitative yields and good enantioselectivities up to 86:14 e.r. under mild reaction conditions. [Copyright &y& Elsevier]

The hetero-Michael reactions among various oxygen, sulfur, and nitrogen nucleophiles and α,β-unsaturated compounds were carried out in the presence of catalytic amounts of o-benzenedisulfonimide as Brønsted acid organocatalyst. The reaction conditions were very mild, and the yields of target products were good. The catalyst was easily recovered and purified, ready to be used in further reactions. This ability grants economic and ecological advantages. Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file. [ABSTRACT FROM PUBLISHER]

A facile and environmentally benign protocol has been developed for the one-pot three-component synthesis of 3,4-dihydropyrimidin-2(1 H)-ones/thiones from the cyclocondensation reaction of aldehyde, ethyl acetoacetate (β-dicarbonyl compound) and urea or thiourea using polyvinylsulfonic acid as a reusable homogeneous Brønsted acid- and metal-free organocatalyst in water and ethanol. This new protocol has the advantages of easy availability, stability, reusability and eco-friendly of the catalyst, high to excellent yields, simple experimental and work-up procedure. Graphical Abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Abstract: A highly enantioselective organocatalytic transfer hydrogenation enabling the synthesis of both 6-fluoro-2-methyltetrahydroquinoline and 7,8-difluoro-3-methyl-benzoxazine has been developed. These key building blocks can for the first time be synthesized using the same methodology allowing fast and efficient, metal-free access to the antibiotic fluoroquinolones flumequine and levofloxacine. [ABSTRACT FROM AUTHOR]

A convenient and efficient organocatalytic procedure for the selective cyclization of 1,3-diketones to give aromatic substituted 4 H -chromen-4-ones under mild reaction conditions using N -triflyl phosphoramide is described. Application of the described conditions is presented in a formal synthesis of ( S )-flavanone. [ABSTRACT FROM AUTHOR]

Abstract: The first example of 2,6-pyridinedicarboxylic acid (PDA)-catalyzed organic reactions was developed in this article. The special bifunctional brønsted acid could be used in the chemoselective acetalization of aldehydes for preparation of corresponding acetals in excellent yields, and the Michael-type Friedel-Crafts reactions of indoles with α,β-unsaturated enones were also promoted by the same catalyst efficiently. [Copyright &y& Elsevier]

The first example of solvent-free, organocatalyzed, polymerization of 1,3-dioxolan-4-ones, used as easily accessible monomers for the synthesis of polylactic acid (PLA), is described here. An optimization of reaction conditions was carried out, with p-toluensulfonic acid emerging as the most efficient Brønsted acid catalyst. The reactivity of the monomers in the tested conditions was studied following the monomer conversion by 1H NMR and the molecular weight growth by SEC analysis. A double activation polymerization mechanism was proposed, pointing out the key role of the acid catalyst. The formation of acetal bridges was demonstrated, to different extents depending on the nature of the aldehyde or ketone employed for lactic acid protection. The polymer shows complete retention of stereochemistry, as well as good thermal properties and good polydispersity, albeit modest molecular weight. [ABSTRACT FROM AUTHOR]