Hydrogen Bond Donor Catalysts Research Articles

Intramolecular Silanoxy-Michael Reactions with Pendant Nitroalkenes: Racemic and Enantioselective.

We present the first racemic and scalemic examples of di-tert-butyl silanoxy-Michael additions. Our operationally simple protocol is selective for nitro-olefins and simply involves stirring the substrate with an appropriate hydrogen-bond donor catalyst without any special precautions to exclude air or moisture. For each substrate examined, we have developed complementary protocols that optimize yield and enantioselectivity. Our reactions scale well, and the products are valuable intermediates for further transformations, including for the preparation of enantioenriched vicinal amino alcohols.

A cobalt templated outer sphere hydrogen bond donor catalyst derived from 2-guanidinobenzimidazole: Synthesis, applications in carbon–carbon bond forming reactions, structure

A lipophilic tricationic cobalt tris(chelate) complex of 2-guanidinobenzimidazole (GBI), [Co(GBI)3]3+ 3BArf– (23+ 3BArf–; BArf = B(3,5-C6H3(CF3)2)4), is prepared from the corresponding hydrophilic trichloride salt and Na+ BArf– or Ag+ BArf– under aqueous/organic biphasic conditions. This racemic chiral complex, which is obtained as a mer isomer and a tetradecahydrate as assayed by NMR and TGA, is an excellent catalyst for additions of dimethyl malonate and indole to trans-ß-nitrostyrenes (10 mol%), and cycloadditions of CO2 to epoxides (1 mol%; solvent-free). Average yields (84 %, 91 %, 81 %) and rates are slightly greater than those obtained with a monocationic ruthenium GBI complex [(η5-C5H5)Ru(CO)(GBI)]+ BArf– prepared earlier. Attempted crystallization of 23+ 3Cl– gives a tetramethanol solvate of a salt derived from loss of two molecules of HCl. This can be represented as [Co(GBI)(GBI–H)2]+ Cl−, and bond lengths and hydrogen bonding motifs are carefully analyzed, especially in the context of dominant chelate resonance forms.

Development of Silica‐Immobilized Material as Heterogeneous Hydrogen Bond Donor (HBD) Catalyst: Synthesis of Cyclic Carbonates from CO2 and Epoxides

AbstractComposite silica materials have been developed by hydrothermal method and utilized as heterogeneous Hydrogen Bond Donor (HBD) catalysts, where the functionalized ketimine derivatives have been immobilized on the solid support. Such functional materials have been found to be efficient catalysts for the synthesis of cyclic carbonates through the installation of CO2 with epoxides. Characterization of these materials was systematically done using various spectroscopic and imaging techniques to confirm the presence of organic compounds on the silica surface. These composite materials exhibited significantly higher catalytic activity as compared to the other homogeneous methods. Additionally, this synthetic process was extremely convenient in terms of all the external parameters such as, solvent free condition at ambient reaction temperature with normal pressure of CO2, very low catalyst loading with proper regeneration and reusability of the catalyst. These facets have definitely made this technique greener and more sustainable.

Development of Suitable Hydrogen Bond Donor (HBD) Catalysts for the Synthesis of Cyclic Carbonates and Dithiocarbonates from Epoxide

Development of Suitable Hydrogen Bond Donor (HBD) Catalysts for the Synthesis of Cyclic Carbonates and Dithiocarbonates from Epoxide

Sustainable Organocatalytic Processes to Access Alkyl SuFEx Click Hubs and Tetrasubstituted Carbon Centers: Potential Libraries for Multidisciplinary Applications

AbstractIn this Account, we provide an overview of our recent achievements on sustainable organocatalysis. Our group has unveiled the effectiveness of specific organocatalysts under various environmentally benign conditions. We have found that N-heterocyclic carbene and phosphazene superbases exhibit favorable performances in bulk aqueous reaction environments. In addition, the use of organic superacid catalysts results in synergistic effects when hydrogen-bond donor catalysts are assembled in aqueous media. Moreover, we discovered that a neutral organic salt precatalyst can generate a potent silylium Lewis acid catalyst in situ, specifically under solvent-free conditions. These innovative, sustainable organocatalytic processes have successfully facilitated the conversion of raw starting materials into valuable compounds, including sulfur(VI) fluoride exchange (SuFEx) click hubs and tetrasubstituted carbon centers incorporating heteroatoms.1 Introduction2 Water-Accelerated N-Heterocyclic Carbene (NHC) Catalysis for β-Aminosulfonyl Fluorides3 Water-Accelerated Phosphazene Superbase Catalysis for β-Sulfidosulfonyl Fluorides and γ-Geminal Dithioester-Incorporated Sulfonyl Fluorides4 Water-Accelerated Synergistic Superacid Catalysis for α-Tertiary Amines5 Solvent-, Metal-, and Purification-Free PPM (parts per million) Neutral Organic Salt Catalysis for Tertiary Cyanohydrin Derivatives6 Conclusion

Post-Modification of Octahedral Chiral-at-Metal Cobalt(III) Complexes by Suzuki–Miyaura Cross-Coupling and Evaluation of Their Catalytic Activity

A family of well-defined Λ- and Δ-configured octahedral cationic chiral-at-cobalt catalysts were expanded through a straightforward postcomplexation of the bromine-functionalized Co(III) complexes based on (R,R)-1,2-cyclohexanediamine and (S,S)-1,2-diphenylethylenediamine by Suzuki–Miyaura cross-coupling reaction (CCR) with arylboronic acids. The corresponding modified Co(III) complexes were isolated by standard silica column chromatography with up to 65% yields. Indeed, it is the first example of the direct modification of the ligand sphere of chiral Co(III) catalysts through Suzuki–Miyaura CCR. It was observed for the first time that the chiral metal center is epimerized during the cross-coupling process at the transmetalation stage on palladium catalyst in the case of minor diastereomers of Co(III) complexes (Δ(R,R)-1 and Λ(S,S)-2). Next, the efficacies of obtained chiral metal-templated complexes 1–4 were evaluated in benchmark asymmetric reactions in order to compare their catalytic activity. Chiral Co(III) complexes 1–4 have been examined as hydrogen bond donor (HBD) catalysts in such important reactions as epoxidation of chalcone and the fixation of CO2 into valuable cyclic carbonates.

Exploring Structure-Function Relationships of Aryl Pyrrolidine-Based Hydrogen-Bond Donors in Asymmetric Catalysis Using Data-Driven Techniques.

Hydrogen bond-based organocatalysts rely on networks of attractive noncovalent interactions (NCIs) to impart enantioselectivity. As a specific example, aryl pyrrolidine substituted urea, thiourea, and squaramide organocatalysts function cooperatively through hydrogen bonding and difficult-to-predict NCIs as a function of the reaction partners. To uncover the synergistic effect of the structural components of this catalyst class, we applied data science tools to study various model reactions using a derivatized, aryl pyrrolidine-based, hydrogen-bond donor (HBD) catalyst library. Through a combination of experimentally collected data and data mined from previous reports, statistical models were constructed, illuminating the general features necessary for high enantioselectivity. A distinct dependence on the identity of the electrophilic reaction partner and HBD catalyst is observed, suggesting that a general interaction is conserved throughout the reactions analyzed. The resulting models also demonstrate predictive capability by the successful improvement of a previously reported reaction using out-of-sample reaction components. Overall, this study highlights the power of data science in exploring mechanistic hypotheses in asymmetric HBD catalysis and provides a prediction platform applicable in future reaction optimization.

Synthesis of Functionalized Five-Membered Heterocycles from Epoxides: A Hydrogen-Bond Donor Catalytic Approach.

The synthesis of highly functionalized five-membered oxa- and aza-heterocycles has been reported utilizing hydrogen-bond donor (HBD) catalysis. In this method, an epoxide was taken as a substrate and reacted with functionalized arylidene/alkylidene malononitrile derivatives in the presence of a newly designed HBD catalyst. In all the cases, the products 2,5-disubstituted tetrahydrofurans (2,5-THFs) were obtained in good to excellent yields (up to 86%) with high diastereoselectivity (dr up to 99:1) as a single regioisomer. The stereochemistry at the 2- and 5-positions of the five-membered ring has been confirmed by single-crystal X-ray analysis, and cis is found to be the major product. The same strategy has been further utilized to obtain substituted oxazolidines whenever the epoxide has been reacted with isocyanate as an electrophile. In order to induce enantioselectivity, a chiral epoxide has been reacted with both the electrophiles in the presence of the same catalyst system to afford the single stereoisomer of the final products. This synthetic methodology involves a low catalyst loading and ambient reaction condition and has been generalized with various substituents present in the starting electrophiles to produce the resultant products in acceptable yields and stereoselectivity.

Charge‐activated TADDOLs: Recyclable organocatalysts for asymmetric (hetero‐)Diels–Alder reactions

AbstractSeveral charge‐containing TADDOL salts were synthesized and used as organocatalysts in asymmetric Diels–Alder and hetero‐Diels–Alder reactions. Their catalytic activity was found to exceed that of a noncharged analog while maintaining or improving upon the enantioselectivity. The enhanced activities of the TADDOL salts enabled them to act as presumed hydrogen bond donor catalysts in the Diels–Alder and hetero‐Diels–Alder reactions of 1,3‐cyclohexadiene with methyl vinyl ketone at 40°C and 2‐phenoxy‐1,3‐butadiene with ethyl glyoxylate at room temperature, respectively. Given the ionic nature of these charge‐activated catalysts, it also proved possible to recycle and reuse the TADDOL without chromatography or the need for a recrystallization.

Enantioselective organocatalytic synthesis of α-allylated dihydroquinolines

An enantioselective anion-binding catalyzed allylation method allowing for rapid access to chiral α-allyl dihydroquinolines has been developed. These chiral N-heterocycles were achieved in good yields (up to 90%) and with up to 89:11 e. r. using a tetrakis-triazole-based hydrogen-bond donor catalyst. The versatility of the allyl moiety in the formed products was further demonstrated by selective post-epoxidation and aziridination reactions, leading to highly decorated chiral molecules with up to four stereocenters and 94:6 e. r.

Rhodium(III) Werner Complexes with 1,2‐Diphenylethylenediamine Ligands: Syntheses, Structures, and Applications as Chiral Hydrogen Bond Donor Catalysts and Agents for Enantiomer Purity Determinations

AbstractReactions of RhCl3 and (S,S)‐1,2‐diphenylethylenediamine (S,S‐dpen) in DMSO at 140 °C give Λ‐[Rh(S,S‐dpen)3]3+3Cl− (Λ‐(S,S)‐43+3Cl−) in 76 % yield. When CH2Cl2/water suspensions are treated with 1.0 equiv. of Na+ B(C6F5)4− or Na+ B(3,5‐C6H3(CF3)2)4−, the mixed salts Λ‐(S,S)‐43+2Cl−B(aryl)4− can be isolated from the organic layers (95–91 %). A wide variety of mixed and non‐mixed salts involving these and other anions (BF4−, ClO4−, I−) are also prepared. The lipophilic salts are highly enantioselective catalysts for the Michael addition of dimethylmalonate to trans‐ß‐nitrostyrene (acetone, 0 °C; 92–85 % ee). The crystal structures of seven solvated salts are determined, and hydrogen bonding between the trications and anions or solvate molecules analyzed. There is a notable affinity of chloride anions for the C3 face of Λ‐(S,S)‐43+, which features three synperiplanar NH groups. Λ‐(S,S)‐43+2I−B(C6F5)4− is an excellent chiral solvating agent for determining enantiomeric purities of chiral organic molecules with hydrogen bond accepting functional groups (11 mol% (average), CDCl3).

Bis(amino)cyclopropenium Ion as a Hydrogen-Bond Donor Catalyst for 1,6-Conjugate Addition Reactions.

The catalytic application of the bis(amino)cyclopropenium ion has been investigated in conjugate addition reactions. The hydrogen atom, which is attached to the cyclopropene ring of bis(amino)cyclopropenium salts, is moderately acidic and can potentially serve as a hydrogen-bond donor catalyst in some organic transformations. This hypothesis has been successfully realized in the 1,6-conjugate addition reactions of p-quinone methides with various nucleophiles such as indole, 2-naphthol, thiols, phenols, and so forth. The spectroscopic studies (NMR and UV-vis) as well as the deuterium isotope labeling studies clearly revealed that the hydrogen atom (C-H) that is present in the cyclopropene ring of the catalyst is indeed solely responsible for catalyzing these transformations. In addition, these studies also strongly indicate that the C-H hydrogen of the cyclopropene ring activates the carbonyl group of the p-quinone methide through hydrogen bonding.

Solvent free enantioselective catalysis with chiral cobalt(iii) Werner complexes via ball milling

The title technique is applied for the first time to cobalt(iii) hydrogen bond donor catalysts, a large family of recently developed salts that enable numerous enantioselective organic reactions and feature an earth abundant metal.

An octahedral cobalt(iii) complex based on cheap 1,2-phenylenediamine as a bifunctional metal-templated hydrogen bond donor catalyst for fixation of CO2 with epoxides under ambient conditions

An octahedral cobalt(iii) complex based on cheap 1,2-phenylenediamine operates as an efficient bifunctional hydrogen bond donor catalyst in cycloaddition of epoxides with CO2 under ambient conditions and solvent- and co-catalyst-free conditions.

A computational study of hydrogen bonding motifs in halide, tetrafluoroborate, hexafluorophosphate, and tetraarylborate salts of chiral cationic ruthenium and cobalt guanidinobenzimidazole hydrogen bond donor catalysts; acceptor properties of the “BArf” anion

The chiral complexes [(η5-C5H5)Ru(CO)(GBI)]+ X− and mer-[Co(GBI)3]3+ 3X−, where GBI is the chelate ligand 2-guanidinobenzimidazole (HN=C(NHH′)NHC(NHR)=NR′), are effective hydrogen bond donor catalysts for a variety of organic reactions. Salts with X− = halide, BF4−, PF6− and BArf− (B(3,5-C6H3(CF3)2)4−) are studied computationally as an initial step in rationalizing reactivity trends and enantioselectivities. A variety of cation/anion hydrogen bonding motifs are identified, some involving a dyad of synperiplanar NH linkages (HN=C(NHH′)NHC(NHR)=NR′), and others (more stable) involving a triad (HN=C(NHH′)NHC(NHR)=NR′). Within each series, the gas phase ΔG values follow the order Cl− (most negative ΔG) < BF4−< PF6− < BArf−, paralleling catalytic activities and (inversely) hydrogen bond acceptor strengths suggested experimentally. With BF4−, all hydrogen bonds involve F-B-F units; with PF6−, both cis-F-P-F and mer-F-PF-F units can bind; with BArf− the isomers feature 2–6 NH⋯FC− and 1–2 NH⋯π interactions. The ΔG values in CH2Cl2 show a few differences in relative stabilities, which are analyzed; in the ruthenium series, free or solvent separated ions are predicted to be the major species for all PF6− and BArf− salts. Crystallographically characterized BArf− salts where the cations possess NH donor groups are analyzed.

Computational Investigations of Enantioselection in Carbon–Carbon Bond Forming Reactions of Ruthenium Guanidinobenzimidazole Second Coordination Sphere Hydrogen Bond Donor Catalysts

The NH2 group of 2-guanidinobenzimidazole (GBI) can be replaced by (RCRC)-NHCH(CH2)4CHNMe2 and elaborated to the enantiopure chelate salts (SRuRCRC)-[(η5-C5H5)Ru(CO)(GBICH(CH2)4CHNMe2)]+PF6– ((SRuRCRC)-2+PF6–) and (RRuRCRC)-2+PF6–. These catalyze highly enantioselective additions of 1,3-dicarbonyl compounds to nitroalkenes. The mechanism and basis for enantioselection are probed by DFT calculations. First, the parent GBI complex [(η5-C5H5)Ru(CO)(GBI)]+PF6– (1+PF6–) is examined. This species has only ruthenium-centered chirality and must be used with a trialkylamine, as it lacks the internal base of 2+PF6–. The dicarbonyl compound initially hydrogen bonds to the NH triad of the GBI ligand, but the transition states leading to each product enantiomer are essentially equal in energy. In contrast, after similar bonding of the dicarbonyl compound to (SRuRCRC)- or (RRuRCRC)-2+PF6–, a proton is transferred to the :NMe2 moiety, giving an enolate and a HNMe2+ group. The latter mediates the introduction of trans-β-nitrostyrene such that one enolate π face attacks the Csi═CrePh face to give an addition product with an R configuration, in agreement with experiment. Thus, the configurations of the catalyst carbon stereocenters control the product stereochemistry. Interactions in competing transition states are analyzed.

Chiral-at-Metal Ruthenium Complexes with Guanidinobenzimidazole and Pentaphenylcyclopentadienyl Ligands: Synthesis, Resolution, and Preliminary Screening as Enantioselective Second Coordination Sphere Hydrogen Bond Donor Catalysts

Pentaphenylcyclopentadienyl ruthenium 2-guanidinobenzimidazole (GBI = HN═C(NHH′)NHC(NHR)═NR′) chelate complexes are accessed by treating (η5-C5Ph5)Ru(CO)2(Br) with Me3NO, GBI, and Ag+PF6–. Chromato...

Chiral Tricationic Tris(1,2-diphenylethylenediamine) Cobalt(III) Hydrogen Bond Donor Catalysts with Defined Carbon/Metal Configurations; Matched/Mismatched Effects upon Enantioselectivities with Enantiomeric Chiral Counter Anions

The enantiopure and diastereopure salts Λ- or Δ-[Co((S,S)-dpen)3]3+ 2Cl–BArf– (Λ- or Δ-(S,S)-13+ 2Cl–BArf–; dpen/BArf = 1,2-diphenylethylenediamine/B(3,5-C6H3(CF3)2)4) and Λ-(S,S)-13+ 3Cl– are trea...

Solvent Dependent Divergent Reactivity of Electron‐Rich Dienones with and without Visible Light: Access to Cyclopropanated Furans and Butenolides

AbstractVisible light excitation of electron‐rich dienones in isopropanol solvent under ambient conditions using hexafluoroisopropanol (HFIP) as an additive promotes intramolecular radical cascade cyclization to afford cyclopropanated furans. Molecular dioxygen in the air serves as a redox catalyst in this reaction which is proposed to proceed through a radical cation intermediate generated by single‐electron transfer (SET) from a phototransient dienone to oxygen. By changing the solvent from isopropanol to HFIP, exclusive formation of substituted butenolides occurs via ionic cascade cyclization involving E→Z isomerization/lactonization/thiolate addition. HFIP is assumed to act as a medium, hydrogen bond donor catalyst, and a Lewis acid substitute as well. This reaction may be conducted even in the absence of light and no catalyst or reagent is required.magnified image

Synthesis and Reactivity of α-Haloglycine Esters: Hyperconjugation in Action.

A general and efficient synthesis of α-haloglycine esters from commercially available feedstock chemicals, in a single step, is reported. The reactivity of these α-haloglycine esters with various nucleophiles was studied as surrogates of α-iminoesters upon activation with hydrogen-bond donor catalysts. DFT calculations on the α-haloglycine structures (X = F, Cl, Br) accompanied by an X-ray characterization of the α-bromoglycine ester support the existence of a "generalized" anomeric effect created by hyperconjugation. This peculiar hyperconjugative effect is proposed to be responsible for the enhanced halogen nucleofugality leading to a facile halogen abstraction by hydrogen-bond donor catalysts. This reactivity was exploited with thiourea catalysts on several catalytic transformations (aza-Friedel-Crafts and Mannich reactions) for the synthesis of several types of non-proteinogenic α-amino esters.