Chiral Superbases Research Articles

Chiral Superbases with Extended Hydrogen Bond Networks.

Extended hydrogen bond networks can substantially increase basicity through stabilization of the resultant conjugate acid. In this study, the chiral superbases (9-11) having anilinyl substituents attached to the prototype superbase 1,8-bis(dimethylamino)naphthalene 1 are examined using DFT methods (PBE1PBE/6-311+G(d,p). While in the gas phase, these are more basic than 1, in THF solution they are slightly weaker bases than 1. While 9-11 are chiral, their rotational barrier about the Caryl-Caryl bond is about 20 kcal mol-1. Aminonaphthyl substituents (18-20) increase the rotational barrier by about 10 kcal mol-1. As a proof-of-concept, deprotonation of propanal by the chiral bases 9-11 is predicted to have ee's ranging from 58% (with 9) to 95% (with 11). The deprotonation of 4- tert-butylcyclohexanone and cyclohexanoxide by 9 are predicted to have modest (23%) and excellent (97%) ee's, respectively.

Chelating P2-Bis-phosphazenes with a (R,R)-1,2-Diaminocyclohexane Skeleton: Two New Chiral Superbases.

The linkage of two P2 -phosphazenyl groups through a C2 -symmetric (R,R)-1,2-diaminocyclohexane (DACH) backbone yielded the new chiral superbases DACH-P2 NMe2 and DACH-P2 Pyr (Pyr=pyrrolidinyl). These bases were prepared by a Kirsanov reaction and studied with respect to their spectroscopic and structural characteristics. Theoretical calculations concerning their basicity properties revealed remarkable pKBH+ values of 38.1 and 39.9 on the acetonitrile scale; this makes them the strongest nonionic chiral superbases known to date.

Two C2-symmetric chelating P2-bisphosphazene superbases connected via a binaphthyl backbone – synthesis, structural features and preparation of a cationic alkyl aluminum complex

Two P2-phosphazenyl groups were linked via a C2-symmetric binaphthyl backbone resulting in two novel chiral superbases with dimethylamino and pyrrolidino substituents. We investigated their basic properties and coordination chemistry towards a cationic alkyl aluminum fragment. The outstanding basicity of the chiral tetrasphosphazenes presented herein leads to interesting perspectives for application in asymmetric Brønsted base catalysis.

Exploiting propane-1,3-diimines as building blocks for superbases: a DFT study

The DFT calculations are employed to construct propane-1,3-diimine as an essential building block to design organic superbases in the gas and acetonitrile phases. This molecular framework is versatile in terms of anchoring different functional groups to achieve higher basicities. Some of these organic superbases showed very high pKa values of ∼40. The influence of iminophosphorane substituents on the propane-1,3-diimine scaffold 4 showed a remarkable enhancement in the basicity, which leads to an increase in the pKa by ∼20 units. The same molecular scaffold also leads to the design of a chiral organic superbase, which keeps a close resemblance to the known ligands for asymmetric synthesis. This newly designed chiral superbase exhibits the highest proton affinity and pKa compared to other reported chiral superbases. The topographical analysis of the molecular electrostatic potential (MESP) has been carried out for some selected compounds at the B3LYP/6-311+G** level of theory. The MESP analyses and steric strain calculations revealed the importance of intrinsic basicity of nitrogen centers and the cation strain effect. To the best of our knowledge, this is the first time that the combination of MESP and strain calculations is employed to segregate the intrinsic basicity of reactive centers and the structural factors responsible for determining the basicities of such organic superbases. The cation resonance effect also plays an important role in enhancing the basicities of the systems studied here. Intramolecular and intermolecular proton transfer barriers have been calculated to examine the kinetic activity of these diimines.

Oxygen Superbases as Polar Binding Pockets in Nonpolar Solvents

A novel class of chiral superbases derived from the 2,2'-bipyridyl-N,N'-dioxide skeleton are presented. Combined experimental and theoretical data reveal that their proton affinities are on the order of 1050 kJ mol(-1), with protonation occurring at the oxygen atoms in a chelating manner. In the free bases, the oxygen atoms form a strongly polar binding site hidden in a hydrophobic envelope formed by the hydrocarbon backbone of the superbases. This chiral molecular structure can entrap polar intermediates or polarized transition structures and stabilize them in nonpolar solvents. Specifically, this mode of catalysis is shown for the coupling of benzaldehyde and allyltrichlorosilane.

Chiral superbases: the proton affinities of 1‐ and 2‐aza[6]helicene in the gas phase

The proton affinities (PAs) of 1- and 2-azahelicene were determined using various mass spectrometric techniques and complementary results from density functional theory. With PAs of about 1000 kJ mol(-1), the helical backbone of both compounds offer promising perspectives for future research on enantioselective reactions of these helical nitrogen bases.

ChemInform Abstract: Modified Guanidines as Chiral Superbases: The First Example of Asymmetric Silylation of Secondary Alcohols.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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.

ChemInform Abstract: Modified Guanidines as Chiral Superbases: Application to Asymmetric Michael Reaction of Glycine Imine with Acrylate or Its Related Compounds.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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.

ChemInform Abstract: Modified Guanidines as Potential Chiral Superbases. Part 2. Preparation of 1,3‐Unsubstituted and 1‐Substituted 2‐Iminoimidazolidine Derivatives and a Related Guanidine by the 2‐Chloro‐1,3‐dimethylimidazolinium Chloride‐Induced Cyclization of Thioureas.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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.

ChemInform Abstract: Modified Guanidines as Potential Chiral Superbases. Part 3. Preparation of 1,4,6‐Triazabicyclooctene Systems and 1,4‐Disubstituted 2‐Iminoimidazolidines by the 2‐Chloro‐1,3‐dimethylimidazolinium Chloride‐Induced Cyclization of Guanidines with a Hydroxyethyl Substituent.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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.

ChemInform Abstract: Modified Guanidines as Potential Chiral Superbases. Part 1. Preparation of 1,3‐Disubstituted 2‐Iminoimidazolidines and the Related Guanidines Through Chloroamidine Derivatives.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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.

Modified guanidines as chiral superbases: the first example of asymmetric silylation of secondary alcohols

Modified guanidines could effectively mediate asymmetric silylation of secondary alcohols as recyclable bases under simple and mild conditions.

Modified guanidines as chiral superbases: application to asymmetric Michael reaction of glycine imine with acrylate or its related compounds

Modified guanidines efficiently catalysed the asymmetric Michael reaction of a prochiral glycine derivative with acrylate or its related compounds either in solution or without a solvent under simple and mild conditions (>95% ee).

Modified guanidines as potential chiral superbases. 2. Preparation Of 1,3-unsubstituted and 1-substituted 2-iminoimidazolidine derivatives and a related guanidine by the 2-chloro-1, 3-dimethylimidazolinium chloride-induced cyclization of thioureas

Simple preparation methods for modified guanidines were explored for new chiral superbases. Thus, (4S,5S)-4,5-diphenyl- and diastereomeric cyclohexane-fused 2-iminoimidazolidines were prepared from (1S,2S)-1,2-diphenylethylenediamine and (1R,2R)- or (1S,2S)-1, 2-diaminocyclohexanes through cyclization of protected thiourea intermediates with 2-chloro-1,3-dimethylimidazolinium chloride (DMC) as a key reaction. In the (4S,5S)-4,5-diphenyl series 1-methyl-2-iminoimidazolidines and 2-diethylaminoimidazoline were also prepared as related guanidines.

Modified Guanidines as Potential Chiral Superbases. 1. Preparation of 1,3-Disubstituted 2-Iminoimidazolidines and the Related Guanidines through Chloroamidine Derivatives

Modified guanidines were explored as potential chiral superbases. Thus, chiral 1,3-dimethyl-2-iminoimidazolidines with or without 4, 5-diphenyl groups, their guanidinium salts, and the 2-iminoimidazolidines with (S)-1-phenylethyl groups on the ring nitrogens were prepared by treatment of 2-chloroimidazolinium chlorides with appropriate amines. Bicyclic guanidines were also prepared from a prolinamide using a similar procedure.

Modified guanidines as potential chiral superbases. 3. Preparation Of 1,4,6-triazabicyclooctene systems and 1,4-disubstituted 2-iminoimidazolidines by the 2-chloro-1,3-dimethylimidazolinium chloride-induced cyclization of guanidines with a hydroxyethyl substituent

Simple preparation methods of modified guanidines have been explored as potential chiral superbases. Thus, 3,7,8-trisubstituted and 3,6,7, 8-tetrasubstituted 1,4,6-triazabicyclooctene systems were prepared from (1S,2S)-1,2-diphenylethylenediamine through stepwise 2-chloro-1, 3-dimethylimidazolinium chloride (DMC)-induced cyclizations of protected thioureas to the corresponding 2-iminoimidazolidines and then of 2-(2-hydroxyethylimino)imidazolidines to the bicyclic systems. Linear guanidines with a 2-hydroxyethyl functional group were prepared by the reaction of carbodiimides with 2-amino alcohols. Reaction of linear-type guanidines with DMC followed by base treatment afforded 1,4-disubstitued 2-iminoimidazolidines. Furthermore, another type of 1,4,6-triazabicyclooctene was also prepared through double DMC-induced cyclization of guanidines with two 2-hydroxyethyl substituents.