Urea Organocatalysts Research Articles

Synthesis and Characterization of New Chiral Polyurea‐Polyurethane Nanocomposites Incorporating Cinchona‐Derived Urea Organocatalysts

AbstractThe field of asymmetric organocatalysis has witnessed significant advancements in recent years, with chiral urea and thioureas emerging as powerful catalysts. In this study, we aimed to design novel polyurea‐polyurethane nanocomposites functionalized with cinchona urea groups, incorporating organoclay and graphene oxide, to serve as heterogeneous organocatalysts in asymmetric synthesis. The synthesis of these polyurea‐polyurethane nanocomposites was achieved through a two‐component polycondensation reaction. The resulting chiral polyurea‐polyurethanes (PU‐PURs) exhibited favorable yields and demonstrated precise control over stereochemistry, resulting in high enantioselectivity. The incorporation of nanocomposites, such as CU‐MMT and graphene oxide (GO), significantly enhanced the catalytic performance of the PU‐PURs. The CU‐MMT nanocomposites exhibited higher catalytic activity, while the PU‐PURs/GO still exhibited enantioselectivity greater than 99 %. Overall, this study highlights the potential of these novel polyurea‐polyurethane nanocomposites as efficient and versatile heterogeneous organocatalysts in asymmetric synthesis.

Molecularly Imprinted Polymers for (Thio)urea Organocatalyst Recovery and Recycling

Molecularly Imprinted Polymers for (Thio)urea Organocatalyst Recovery and Recycling

Isoselective Ring-opening Polymerization of Racemic Lactide Catalyzed by N-heterocyclic Olefin/(Thio)urea Organocatalysts

The isoselective ring-opening polymerization of racemic lactide was achieved by combining N-heterocyclic olefin (NHO) with mono(thio)ureas or bis(thio)ureas as catalytic systems. The polymerization process shows high stereoselectivity, controllability and reactivity, delivering multi-block isotactic polylactides with high chain-end fidelity and narrow molecular weight distributions. The enhancement of catalytic performance was observed in the following order: bisthiourea (DTU) < monothiourea (TU) < bisurea (DU) < urea (U). The highest Pm (probability of forming a meso dyad) = 0.91 was observed at −70 °C when using NHO/U1 catalytic system and the high stereoselectivity was attributed to chain-end control mechanism.

Studies on the influence of saccharide fragment of urea organocatalysts on the yield and enantioselectivity of aza-Henry reaction

Studies on the influence of saccharide fragment of urea organocatalysts on the yield and enantioselectivity of aza-Henry reaction

The mechanistic duality of (thio)urea organocatalysts for ring-opening polymerization.

Among the various catalysts for ROP, H-bonding organocatalysts stand out in the precise level of reaction control they are able to render during ROP. The H-bonding class of organocatalysts are thought to effect ROP via dual activation of both monomer and chain end. (Thio)urea mediated ROP has experienced a renaissance as a new polymerization mechanism - mediated by imidate or thioimidate species - facilitates new modes of reactivity and new synthetic abilities. Indeed, the urea class of H-bond donors has been shown to be more active than their corresponding thioureas. The imidate mechanism remains highly active in polar solvents and exhibits remarkable control - and 'living' behavior - under solvent-free conditions, and a broad range of temperatures is accessible. The advancements in synthetic abilities have all evolved through a greater understanding of reaction mechanism. Through the continued synergistic advances of catalysis and material, the (thio)urea class of catalyst can find use in a host of potential applications, research and industrial environments.

Steric effects of pH switchable, substituted (2-pyridinium)urea organocatalysts: a solution and solid phase study

ABSTRACTThe study of hydrogen bonding organocatalysis is rapidly expanding. Much research has been directed at making catalysts more active and selective, with less attention on fundamental design strategies. This study systematically increases steric hindrance at the active site of pH switchable urea organocatalysts. Incorporating strong intramolecular hydrogen bonds from protonated pyridines to oxygen stabilizes the active conformation of these ureas thus reducing the entropic penalty that results from substrate binding. The effect of increasing steric hindrance was studied by single crystal X-ray diffraction and by kinetics experiments of a benchmark reaction.

Bifunctional iminophosphorane superbases: Potent organocatalysts for enantio- and diastereoselective Michael addition reactions

Bifunctional iminophosphorane (BIMP) organocatalysts catalyze the enantio- and diastereoselective Michael additions of high pKa cyclic malonamate ester pro-nucleophiles to nitroalkenes with reactivity profiles of up to 3 orders of magnitude greater than tertiary amine bifunctional Brønsted base/(thio)urea organocatalysts. The unrivalled performance of the BIMPs allows reaction times of challenging reactions to be slashed from weeks to minutes and has enabled new flow chemistry applications using polystyrene-supported versions contained within a flow reactor.

Role of Configuration at C6 in Catalytic Activity of l-Proline-Derived Bifunctional Organocatalysts.

l-Proline-derived chiral bifunctional (thio)urea organocatalysts epi-PTU and epi-PU were newly synthesized, and their catalytic performances were compared with their C6 epimeric catalysts PTU and PU in various Michael reactions of nitrostyrene in terms of reactivities and stereoselectivities. The experimental results indicate that a proper relative stereochemistry at C2 and C6 in l-proline-derived bifunctional organocatalysts is important for successful catalysis and that catalysts (PTU and PU) with the 2S,6R configuration are much more efficient.

Chloramphenicol base chemistry. Part 10 : Asymmetric synthesis of α-hydroxy chiral alcohols via intramolecular Michael additions of γ-hydroxy-α, β-unsaturated enones with chloramphenicol base derived bifunctional urea organocatalysts

We have developed the chloramphenicol base urea-catalyzed intramolecular Michael addition of γ-hydroxy-α, β-unsaturated enones. The oxidation of the resulting products provided facile access to the corresponding α-hydroxy chiral alcohols with good efficiency and enantioselectivity, with the reaction displaying broad substrate scope. The utility of this methodology was further demonstrated by the synthesis of (R)-2-hydroxy-4-phenylbutanoate, which is a key building block for the construction of the ACE inhibitor benazepril hydrochloride.

ChemInform Abstract: (Thio)urea‐Catalyzed Formation of Heterocyclic Compounds

AbstractReview: 182 refs.

ChemInform Abstract: (Thio)urea‐Mediated Benzoxazinone Opening: Mild Approach Towards Synthesis of O‐(Substituted Amido)benzamides.

C-terminal activation of N-acylated o-aminobenzoic acids and their derivatives during coupling reactions with amines would often pose a challenge due to the formation of a benzoxazinone intermediate, which may resist reacting with amines. This communication reports a mild approach towards the installation of an amide bond via benzoxazinone ring opening utilizing Schreiner's (thio)urea organocatalyst.

ChemInform Abstract: Enantioselective Oxidation of 1,2‐Diols with Quinine‐Derived Urea Organocatalyst.

Quinine-derived urea has been identified as a highly efficient organocatalyst for the enantioselective oxidation of 1,2-diols using bromination reagents as the oxidant. This simple procedure utilizes readily available reagents and operates at ambient temperature to yield a wide range of α-hydroxy ketones in good yield (up to 94%) and excellent enantioselectivity (up to 95% ee).

Enantioselective Oxidation of 1,2-Diols with Quinine-Derived Urea Organocatalyst

Quinine-derived urea has been identified as a highly efficient organocatalyst for the enantioselective oxidation of 1,2-diols using bromination reagents as the oxidant. This simple procedure utilizes readily available reagents and operates at ambient temperature to yield a wide range of α-hydroxy ketones in good yield (up to 94%) and excellent enantioselectivity (up to 95% ee).

(Thio)urea-mediated benzoxazinone opening: mild approach towards synthesis of o-(substituted amido)benzamides

C-terminal activation of N-acylated o-aminobenzoic acids and their derivatives during coupling reactions with amines would often pose a challenge due to the formation of a benzoxazinone intermediate, which may resist reacting with amines. This communication reports a mild approach towards the installation of an amide bond via benzoxazinone ring opening utilizing Schreiner's (thio)urea organocatalyst.

(Thio)urea Organocatalyst Equilibrium Acidities in DMSO

Bordwell's method of overlapping indicators was used to determine the pK(a) values of some of the most popular (thio)urea organocatalysts via UV spectrophotometric titrations. The incremental effect of CF(3) groups on acidic strength was also investigated. The pK(a)'s are in the range of 8.5-19.6. The results may lead to a better understanding of noncovalent organocatalysis and may aid in future catalyst development.

Enantio- and diastereoselective addition of cyclohexylMeldrum's acid to β- and α,β-disubstituted nitroalkenesvia N-sulfinyl urea catalysis

Using N-sulfinyl urea catalysis, a method has been developed for the asymmetric synthesis of biologically important γ-amino acids with a high level of efficiency, practicality and unprecedented control of multiple stereocenters. This method is based upon the highly enantio- and diastereoselective addition of cyclohexyl Meldrum's acid as an easily deprotectable monocarboxylic acid equivalent. The addition to both β-substituted and α,β-disubstituted nitroalkenes using N-sulfinyl urea organocatalyst 8 is described. The utility of this new method toward drug production is demonstrated by the mole scale preparation of a key precursor to the commercial drug Lyrica using catalyst 8 at only 0.2 mol% loading. Moreover, α,β-disubstituted nitroalkene addition products were efficiently converted to γ-amino acid derivatives without epimerization of either stereocenter.

Enantioselective Addition of Thioacetic Acid to Nitroalkenes via N-Sulfinyl Urea Organocatalysis

The highly enantioselective addition of thioacetic acid to nitroalkenes using a new sulfinyl urea organocatalyst is described. The addition of thioacetic acid proceeds in high yields and enantioselectivities for a variety of aromatic and aliphatic nitroalkene substrates. This new method is useful for preparing chiral 1,2-aminothiol derivatives, as demonstrated by the first enantioselective synthesis of the clinically used antifungal drug sulconazole.

ChemInform Abstract: Enantioselective Aza‐Henry Reaction with an N‐Sulfinyl Urea Organocatalyst.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Asymmetric Morita-Baylis-Hillman Reaction of Arylaldehydes with 2-Cyclohexen-1-one Catalyzed by Chiral Bis(Thio)urea and DABCO

Novel bis(thio)urea organocatalysts were synthesized from axially chiral (R)-(-)-5,5',6,6',7,7',8,8'-octahydro-1,1'-binaphthyl-2,2'-diamine (H8-BINAM), and their catalytic abilities have been examined in the Morita-Baylis-Hillman reaction of 2-cyclohexen-1-one or 2-cyclopenten-1-one with a wide range of aromatic aldehydes in combination with DABCO. The best result was achieved in the reaction of 3-fluorobenzaldehyde with 2-cyclohexen-1-one to give the desired Morita-Baylis-Hillman product in 79% yield and 88% ee.

Enantioselective Aza-Henry Reaction with an N-Sulfinyl Urea Organocatalyst

A new class of organocatalyst has been developed that incorporates a sulfinyl group as a urea or thiourea substituent. The sulfinyl group serves to simultaneously acidify the urea and provide asymmetric induction in hydrogen-bond-catalyzed reactions. The utility of this new catalyst structure is demonstrated by the high selectivity provided in the aza-Henry reaction not only for aromatic N-Boc imine substrates but also for aliphatic imines for which enantioselective H-bonding catalysis has not previously been demonstrated.