Chiral Base Catalyst Research Articles

Vinylidene ortho-Quinone Methides: Unique Chiral Reaction Intermediates in Catalytic Asymmetric Synthesis.

Vinylidene ortho-quinone methides (VQMs) are one-carbon elongated homologues of ortho-quinone methides (QMs), well-known as useful reaction intermediates in organic transformations. These related quinone methides are quite distinct in terms of stereochemistry. Namely, VQMs are characterized by an exocyclic allenyl ketone unit merged with a dearomatized ring system and thus, can be rendered axially chiral by locating a substituent properly at the terminal methylene group of the allene moiety. It should be also noted that VQMs are tautomers of ortho-ethynylphenols and these isomeric species are correlated through a proton-shift (tautomerization). Focusing on these stereochemical and structural features, we have pursued the development of unprecedented asymmetric reactions involving enantioenriched VQM intermediates generated by chiral-base-catalyzed tautomerization of the ethynylphenol precursors. Indeed, commonly used chiral base catalysts such as cinchonine (CN) and cinchonidine (CD) have been successfully demonstrated to be effective to this end. In this account, we wish to briefly describe our recent studies on the asymmetric syntheses of optically active indeno[1,2-c]chromenes, benzofuro[3,2-b]indeno[1,2-c]chromenes, and benzo[a]carbazoles, based on the catalytic enantioselective generation of VQMs with CN or CD and the stereocontrolled intramolecular follow-up cyclization with tethered alkynes, benzofurans, and indoles, respectively.

Asymmetric Synthesis of Axially Chiral Benzocarbazole Derivatives Based on Catalytic Enantioselective Hydroarylation of Alkynes.

A new synthetic approach to novel axially chiral benzocarbazole derivatives based on the highly enantioselective intramolecular hydroarylation (94-96% ee) of linked alkyne-indole systems by using the prevalent chiral base catalyst, cinchonidine or cinchonine, under unprecedented transition-metal-free conditions is described. The process is considered to involve chiral base catalysis for enantioselective transformation of the alkyne part to a reaction intermediate with an axially chiral vinylidene o-quinone methide (VQM) functionality, which subsequently effects stereospecific cyclization with the tethered indole moiety.

Chiral Functionalization of a Zirconium Metal-Organic Framework (DUT-67) as a Heterogeneous Catalyst in Asymmetric Michael Addition Reaction.

DUT-67, an 8-connected zirconium and 2,5-thiophenedicarboxylate-based metal-organic framework (MOF), was postsynthetically functionalized by l-proline via solvent-assisted linker incorporation to obtain a chiral base catalyst. The parent monocarboxylate could be almost completely exchanged by l-proline after 5 days of treatment. The resulting chiral DUT-67 was demonstrated to be a promising heterogeneous catalyst for the asymmetric Michael addition of cyclohexanone to trans-β-nitrostyrene with excellent yield (up to 96%) and enantioselectivity comparable to that of l-proline in homogeneous reaction (ee of approximately 38%). The Zr-MOF could be reused at least five times without substantial degradation in the crystallinity or catalytic activity. No leaching of catalytically active species into the liquid phase was detected over five cycles.

A Facile Approach to Optically Active Hydroquinoline-2-carboxylates by a One-Pot Asymmetric Michael/Transamination/Cyclization Process.

An efficient one-pot synthesis of optically active hydroquinoline-2-carboxylates from 1,3-cyclohexanediones, β,γ-unsaturated α-keto ester, and benzylamine in the presence of a chiral base catalyst and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) with good diastereoselectivity and high enantioselectivity is described. The reaction proceeds by a sequential asymmetric Michael/transamination/cyclization process.

Chiral Iminophosphoranes-An Emerging Class of Superbase Organocatalysts.

Chiral Brønsted base catalysis is a fascinating and highly explored field of research. For many years catalysts based on chincona alkaloid chiral scaffolds have constituted privileged systems widely employed in numerous base-promoted organic transformations. Recently, a novel group of chiral base catalysts has been successfully introduced. The application of organosuperbases, namely cyclopropenimines, guanidines, and iminophosphoranes, as chiral catalysts is receiving increasing attention. The aim of this Concept article is to summarize recent progress in the field of chiral iminophosphorane superbase organocatalysis. Catalysts design, different approaches to their synthesis, and applications in asymmetric synthesis are outlined and discussed in detail.

Per-6-amino-β-cyclodextrin as a Chiral Base Catalyst Promoting One-Pot Asymmetric Synthesis of 2-Aryl-2,3-dihydro-4-quinolones

A highly efficient one-pot synthesis of enantiomerically enriched 2-aryl-2,3-dihydroquinolin-4(1H)-ones has been carried out for the first time using per-6-ABCD as a supramolecular host, chiral base catalyst, and a reusable promoter to give the corresponding scaffold with high yield (up to 99%) and enantiomeric excess (up to 99%). The catalyst is recovered and reused without loss in its activity.

ジエンの活性化を基盤とする触媒的Ｄｉｅｌｓ‐Ａｌｄｅｒ反応の開発と生理活性シクロヘキセンオキシド類およびカルバ糖類合成への応用

The base-catalyzed Diels-Alder (DA) reaction is a unique cycloaddition, which comprises the combination of electron deficient dienophiles and dienes having acidic functional groups that are activated by bases. It is quite opposite to the well-known Lewis acid-catalyzed DA reactions that include electron rich dienes and dienophiles that are activated by Lewis acids or Bronsted acids. In our continuous effort to develop the base-catalyzed DA, we have found that three different classes of compounds, 3-hydroxy-2-pyrone, 3-hydroxy-2-pyridone, and α-tropolone can be used as dienes suitable for the DA reaction. All the base-catalyzed DA reactions we have developed are accelerated by mild amine bases and give the corresponding products in quantitative to moderate yields. As well as acid-catalyzed DA reactions, chiral base catalysts and/or chiral dienophiles provide the enantioselective DA reactions. Because the resulting DA adducts that have various functional groups and rigid bicyclic ring systems, are attractive building blocks for natural products, particularly for cyclohexene oxides and carbasugars, some synthetic applications to give biologically active compounds using the DA adducts are described.

Binaphthyl-Derived Mono-, Bi- and Multi-Functional Lewis and Brønsted Base Organocatalysts: A New Vista for Asymmetric Synthesis

Lewis and Bronsted base catalysis are rapidly growing areas in organocatalysis. Numerous binaphthyl-derived chiral base catalysts has been developed over the last years. Recent progress in the chiral Lewis and Bronsted base catalysis has been reviewed with a focus being placed on mono-functional catalysts, including primary and secondary diamines, guanidines, phosphines and phosphineoxides; bi- and multifunctional catalysts, covering secondary and/or tertiary amine and phosphine derivatives assisted with urea/thiourea hydrogen bond donors or Lewis/ Bronsted acids. Keywords: Asymmetric organocatalysis, bi-/multi-functional catalysis, binaphthyl-derived organocatalysts, Bronsted bases, Lewis bases, urea/thioureas, Primary Diamines, Guanidine Derivatives, Secondary Diamines, Chiral Phosphineoxides, Alcohol-Assisted Tertiary Amines, B- OR LI-BINOL COMPLEXES, phase transfer catalysts (PTC), tetramethylguanidine (TMG), chemoselective

Asymmetric Baylis—Hillman Reaction: Use of Novel Chiral Aldehydes as Electrophiles, Chiral Base Catalysts and Auxiliaries

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, please click on HTML or PDF.

Asymmetric Baylis-Hillman Reaction: Use of Novel Chiral Aldehydes as Electrophiles, Chiral Base Catalysts and Auxilliaries&#

Asymmetric Baylis-Hillman Reaction: Use of Novel Chiral Aldehydes as Electrophiles, Chiral Base Catalysts and Auxilliaries&#

Structure−Property Relationship in py-Hexahydrocinchonidine Diastereomers: Ab Initio and NMR Study

Two py-hexahydrocinchonidine diastereomers were selectively obtained in the heterogeneous catalytic hydrogenation of cinchonidine over supported Pt catalyst. The two isolated compounds when used as chiral base catalysts in the Michael addition of a beta-keto ester to methyl vinyl ketone gave products of opposite configuration in excess. To trace the reason of this behavior, in the present study, the structures of the two diastereomers were fully optimized by ab initio quantum chemical calculation. These results were then compared with several nuclear Overhauser enhancement spectroscopy (NOESY) signal intensities from the spectra of the two compounds. Further we performed a conformational search on all the optimized geometries independently for the two flexible torsional angles, which are linking the quinuclidine and tetrahydroquinoline moieties present in these molecules. This study allowed us to propose the configuration of the C(4)(') chiral center. Thus, the product mixture resulted in the hydrogenation of cinchonidine containing the 4'-(S)-diastereomer in excess (de = 20%). According to the computation results the 4'-(S)-diastereomer is more stable than the 4'-(R)-diastereomer. The 4'-(S)-conformer obtained by computation has lower electronic energy than the structures obtained for the 4'-(R)-diastereomer, which may explain the excess formation of the first one. The results of the Michael addition catalyzed by these diastereomers were interpreted on the basis of these conclusions.

N‐Methylprolinol Catalysed Asymmetric Baylis−Hillman Reaction

AbstractN‐methylprolinol is used as a chiral base catalyst for the Baylis–Hillman reaction to obtain the adducts in good yields with moderate to good enantioselectivities in 1,4‐dioxane:water (1 : 1, v/v) under ambient conditions.

Enantioselective catalysis. Part 133: Conformational analysis of amides of 9-amino(9-deoxy)epicinchonine

Amides of 9-amino(9-deoxy)epicinchonine have been used as chiral base catalysts to induce asymmetry in enantioselective decarboxylation reactions. To understand the reaction mechanism and to optimize the bases by variation of the amide substituents, a detailed knowledge of their preferred conformation is necessary. The conformations were investigated by 1H NMR spectroscopy, X-ray analysis and semi-empirical molecular orbital calculations. Principally, cinchona alkaloids may adopt four different conformations (Fig. 1 ), of which openb and openb′ are preferred by 2-ethoxy-N-(9-deoxyepicinchonine-9-yl)benzamide 2 in solution. AM1 Calculations confirm these results, and the small energy barrier between the two open conformations explains their simultaneous existence in solution. Crystal structure analyses of various amides show open conformations in the solid state. Local minimum energy conformations were found for open conformations of the compound 2 protonated at the quinuclidine system, which is the active species in the enantioselective decarboxylation reaction.

Asymmetric catalysis, CIII: EnantioselectiveMichael addition of 1,3-dicarbonyl compounds to conjugated nitroalkenes

Optically activeMichael adducts were synthesized by addition of 1,3-dicarbonyl compounds to conjugated nitroalkenes. Good chemical yields were obtained for nitroalkenes stabilized by an aromatic substituent without any further substituents at the double bond. Acetylacetone and methyl-2,3-dihydro-1-oxo-1H-indene-2-carboxylate were used asMichael donors and four cinchona alkaloids as chiral base catalysts. Enantiomeric excess determinations were performed by1H NMR spectroscopy in the presence of thePirkle alcohol and by HPLC on chiral stationary phases. A correlation between the relative configuration of the prevailing isomer of theMichael adduct and the catalysts was established.

ChemInform Abstract: New Entry to Chiral Base Catalyst. Asymmetric Michael Addition of . alpha.‐Substituted β‐Keto Esters to Methyl Vinyl Ketone Catalyzed by Podand‐Type Alkali Metal 2′‐Substituted 1,1′‐Binaphthalen‐2‐oxides.

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.

New Entry to Chiral Base Catalyst. Asymmetric Michael Addition of α-Substituted β-Keto Esters to Methyl Vinyl Ketone Catalyzed by Podand-type Alkali Metal 2′-Substituted 1,1′-Binaphthalen-2-oxides

Abstract Asymmetric Michael reactions of α-substituted β-keto esters with methyl vinyl ketone catalyzed by 10 mol% of sodium 2′-[2-(2-methoxyethoxy)ethoxy]-1,1′-binaphthalen-2-oxide gave the optically active adducts quantitatively in up to 64% enantiomeric excess.