Chiral Phase-transfer Catalysts Research Articles

Effective asymmetric vinylogous Mannich reaction of isatin imines with α,α-dicyanoolefins in the presence of a simple chiral amide phosphonium bifunctional phase transfer catalyst

A Mannich reaction between N-Boc isatin imine and α,α-dicyanoolefin as well as subsequent oxidative cleavage of the malonic nitrile moiety were described.

Chemoselective N-Difluoromethylation of Functionalized Tertiary Amines.

A practical, convenient, and general method for the difluoromethylation of tertiary amines, using diethyl bromodifluoromethylphosphonate and fluoride, is described. This commercially available phosphonate smoothly reacts with a fluoride ion to liberate a difluorocarbene intermediate that in the presence of a proton source and a tertiary amine generates the corresponding α-difluoromethylammonium compound in good to excellent yields. Despite the involvement of a difluorocarbene intermediate, this difluoromethylation occurs almost exclusively on the nitrogen atom with diverse molecular structures, including drugs, surfactants, chiral phase transfer catalysts, polymers, ionic liquids, and other fine chemicals. A preliminary assessment of the effects that an α-difluoromethyl groupT has on hydrogen bonding and logP of quaternary ammonium salts is also described.

Crown ether derived from d-glucose as an efficient phase-transfer catalyst for the enantioselective Michael addition of malonates to enones

A monoaza-15-crown-5 lariat ether derived from d-glucose 1 has been applied as a chiral phase-transfer catalyst in the Michael addition of diethyl, dimethyl, diisopropyl and dibenzyl malonates to enones under mild conditions to afford the adducts with good to excellent enantioselectivities. In the reaction of diethyl malonate with substituted trans-chalcone, the adducts with in enantioselectivities up to 89% ee. Among the reactions of substituted diethyl malonates, those of diethyl acetoxymalonate gave the best results (96% ee). The effect of the substituents of the chalcone was also investigated in reactions with diethyl acetoxymalonate. Among the chalcones substituted on the β-aryl, the para-substituted compounds resulted in the highest enantioselectivities (88–97% ee). The substituents on the benzoyl aryl of chalcone caused a decrease in the enantioselectivity compared to the unsubstituted case. The adducts with furyl or thiophenyl substituents were formed with >99% ee. The glucose-based catalyst also proved to be effective in the cases of diisopropyl and dibenzyl acetoxymalonates (including ees up to 99% ee). The reactions of diethyl acetoxymalonate with cyclic enones gave the corresponding Michael adducts with enantioselectivities up to 83%. The absolute configuration of one of the new Michael adducts was determined by CD spectroscopy.

Helical structures of homo-chiral isotope-labeled α-aminoisobutyric acid peptides

The chiral deuterium- and 13C-isotope-labeled α-aminoisobutyric acids CD3-Aib and 13CH3-Aib were enantioselectively synthesized from L-Ala aldimine using simplified Maruoka chiral phase-transfer catalysts. Homo-chiral (S)-CD3-Aib homopeptides, up to decamers, were prepared. A (R)-CD3-Aib polymer and (S)-13CH3-Aib polymer were also prepared. Conformational studies on homopeptides using CD spectra and an X-ray crystallographic analysis revealed that the preferred conformations were 310-helical structures comprising equal amounts of right-handed (P) and left-handed (M) helical-screw structures. The α-carbon chiral centers induced by the D- or 13C-isotope substitution of Aib were incapable of controlling the helical-screw directions of their oligopeptides and short polymers.

ChemInform Abstract: A New Generation of Chiral Phase‐Transfer Catalysts

AbstractReview: 44 refs.

ChemInform Abstract: Synthesis, Applications and Mechanistic Investigations of C2 Symmetric Guanidinium Salts.

AbstractA series of C2 symmetric guanidinium salts are prepared as chiral phase transfer catalysts and applied to the alkylation of a glycinate Schiff′s base and to the epoxidation of some chalcones.

ChemInform Abstract: Development of a Phase‐Transfer‐Catalyzed, [2,3]‐Wittig Rearrangement.

AbstractThe asymmetric [2,3]‐sigmatropic rearrangement of cyclic (allyloxy)carbonyl compounds (II) and (IV) in the presence of chiral phase transfer catalysts such as (I) is presented.

ChemInform Abstract: Chiral Phase Transfer Catalysts for the Synthesis of Chiral N‐Heterocycles via Asymmetric Cascade Reactions.

AbstractA chiral phase transfer catalyst is used in the reaction of 2‐cyanobenzaldehyde with active methylene compounds.

ChemInform Abstract: Unexpected Solvent/Substitution‐Dependent Inversion of the Enantioselectivity in Michael Addition Reaction Using Chiral Phase Transfer Catalysts.

AbstractNew cinchonium salts (I) are used as chiral phase transfer catalysts in the asymmetric Michael addition of chalcones with diethylmalonate.

Highly enantioselective asymmetric Henry reaction catalyzed by novel chiral phase transfer catalysts derived from cinchona alkaloids.

A new type of di-site chiral phase transfer catalyst has been designed and synthesized from cinchona alkaloids as a chiral precursor. The prepared catalysts are applied in the asymmetric Henry reaction to a wide range of aldehydes using mild concentrations of a base and solvent and under room-temperature conditions. Under the optimized reaction conditions, the highest chemical yields up to 99% along with an excellent enantiomeric excess (ee) up to 99% were obtained using the prepared cinchona alkaloid based chiral phase transfer catalysts.

A new generation of chiral phase-transfer catalysts.

Phase-transfer catalysis has long been recognized as a versatile method for organic synthesis. In particular, over more than the past three decades, asymmetric phase-transfer catalysis based on the use of structurally well-defined chiral catalysts has become a topic of great scientific interest. Although various effective chiral catalysts have already been reported and these catalysts were utilized for practical asymmetric transformations, further design and development of new chiral phase-transfer catalysts are still attractive research subjects in organic chemistry due to the high utility and practicability of phase-transfer-catalyzed reactions. This review focuses on the recent examples of newly designed effective chiral phase-transfer catalysts.

A New Class of Squaramide-Containing Phase-Transfer Catalysts: Application to Asymmetric Fluorination of β-Keto Esters

The squaramide moiety has proven to be a powerful hydrogen-bonding donor in organocatalysis, but chiral phase-transfer catalysts bearing the squaramide motif have not been reported so far. Reported herein is this kind of catalyst and their catalytic performance in the asymmetric fluorination of β-keto esters.

A new class of bifunctional chiral phase transfer catalysts for highly enantioselective asymmetric epoxidation of α,β-unsaturated ketones at ambient temperature

A new type of bis-quaternary ammonium bromide as chiral multifunctional phase transfer catalysts derived from readily available inexpensive cinchona alkaloids has been developed and evaluated for the enantioselective asymmetric epoxidation of various chalcones in the presence of lower concentrations of various oxidants, bases, solvents and ambient temperature conditions. Under optimized reaction conditions, highest chemical yields of up to 98% along with the excellent enantioselectivities of about 99% were obtained by using the cinchona based chiral multifunctional phase transfer catalysts.

Unexpected solvent/substitution-dependent inversion of the enantioselectivity in Michael addition reaction using chiral phase transfer catalysts

New cinchonium salts bearing 5,5′-bis(methyl)-2,2′-bipyridine 1 group show solvent/substitution-dependent reversal of enantioselectivity. When used as chiral phase transfer catalyst in the asymmetric Michael addition of chalcones with diethylmalonate within two hours these catalysts result in high chemical yield (up to 98%) and enantiomeric excess (up to 99%) under lower concentrations of base and cold conditions.

ChemInform Abstract: Highly Enantioselective Michael Addition Reactions with New Trimeric Chiral Phase Transfer Catalysts.

AbstractTwo new multi‐site phase transfer catalysts are introduced for the enantioselective Michael addition reactions of various chalcones with diethyl malonate.

Organic chemistry: Natural polarity inverted.

The concept of umpolung describes the reversal of the naturally occurring electrostatic polarization of chemical groups. It has now been used to make single mirror-image isomers of nitrogen-containing molecules. See Letter p.445 Imines, carbon–nitrogen double bonds, act as electrophiles towards carbon nucleophiles in the synthesis of amines, but the range of synthesizable amines could be greatly extended if the carbon atom of the imine could be rendered electron-rich to allow it to act as a nucleophile towards a carbon electrophile. Li Deng and colleagues have developed a procedure that achieves just that. They report the discovery and development of new chiral phase transfer catalysts that promote highly efficient asymmetric reactions of imines and enals. The reaction provides a conceptually new and practical approach towards the synthesis of chiral amino compounds.

Catalytic asymmetric umpolung reactions of imines.

Imines, carbon-nitrogen double bonds, are fundamentally important functional groups in organic chemistry. This is largely due to the fact that imines act as electrophiles in C–C bond forming reactions towards carbon nucleophiles, thereby serving one of the most widely used precursors for the formation of amines in both synthetic and biosynthetic settings.1–5 If the carbon atom of the imine could be rendered electron-rich, the imine could react as a nucleophile instead of as an electrophile. Such a reversal in the electronic characteristics of the imine functionality would facilitate the development of new chemical transformations that convert imines into amines via C–C bond forming reactions with carbon electrophiles, thereby creating new opportunities for the efficient synthesis of amines. The development of asymmetric ‘umpolung’ reactions of imines remains an uncharted ground, in spite of the far-reaching impact of such reactions in organic synthesis. Here we report the discovery and development of new chiral phase transfer catalysts that promote the highly efficient asymmetric umpolung reactions of imines and enals. These catalysts mediate the deprotonation of imines and direct the 2-azaallylanions thus formed to react in a highly chemoselective, regioselective, diastereoselective and enantioselective fashion with enals. The reaction tolerates a broad range of imines and enals, and can be carried out in high yield with as little as 0.01 mol % catalyst with a moisture and air-tolerant operational protocol. These umpolung reactions provide a conceptually new and practical approach towards chiral amino compounds.

Dipeptide-Derived Multifunctional Quaternary Phosphonium Salt Catalyzed Asymmetric Cyclizations via a Tandem Michael Addition/SN 2 Sequence.

A novel family of dipeptide-based multifunctional quaternary phosphonium salts has been developed as chiral phase-transfer catalysts, which feature ready accessibility and structure modularity, allowing easy fine-tunings of activity. They demonstrated high efficiency in catalyzing the tandem asymmetric Michael addition/intramolecular SN 2 reaction between 6 or 7-substituted conjugate enones and malonates, providing synthetically important five or six-membered carbocycles and heterocycles in good yields and with good to excellent enantioselectivities.

ChemInform Abstract: Ultrasonic Assisted Dimeric Cinchona Based Chiral Phase Transfer Catalysts for Highly Enantioselective Synthesis of Epoxidation of α,β‐Unsaturated Ketones.

ChemInform Abstract: Ultrasonic Assisted Dimeric Cinchona Based Chiral Phase Transfer Catalysts for Highly Enantioselective Synthesis of Epoxidation of α,β‐Unsaturated Ketones.

The asymmetric alkylation reaction of glycine derivatives catalyzed by the novel chiral phase transfer catalysts

Herein a new series of chiral phase transfer catalysts derived from the cinchona alkaloids were synthesized and applied in the asymmetric alkylation of glycine derivatives with high yields and moderate to excellent ee values (39.5–99.7%).