Daisuke Uraguchi

Chiral Organic Ion Pair Catalysts Assembled Through a Hydrogen-Bonding Network

Catalytic Assembly Most asymmetric catalysts employed in organic chemistry are assembled through binding of chiral ligands to one or more metal ions. Uraguchi et al. (p. 120, published online 27 August) show that a highly selective catalyst can assemble through hydrogen bonding from a small collection of small molecules in the absence of metals. In the solid state, the catalyst comprises a central chiral phosphonium cation bound to two phenol molecules, which in turn bind a charge-compensating phenoxide ion. In solution, an oxazolone derivative appears to be able to bind in place of the phenoxide, spurring its stereoselective addition to a broad range of esters. A small cluster of hydrogen-bonded molecules acts as a highly selective asymmetric catalyst. Research to develop structurally discrete, chiral supramolecular catalysts for asymmetric organic transformations has met with limited success. Here, we report that a chiral tetraaminophosphonium cation, two phenols, and a phenoxide anion appear to self-assemble into a catalytically active supramolecular architecture through intermolecular hydrogen bonding. The structure of the resulting molecular assembly was determined in the solid state by means of x-ray diffraction analysis. Furthermore, in solution the complex promotes a highly stereoselective conjugate addition of acyl anion equivalents to α,β-unsaturated ester surrogates with a broad substrate scope. All structural components of the catalyst cooperatively participate in the stereocontrolling event.

Chiral tetraaminophosphonium carboxylate-catalyzed direct Mannich-type reaction.

The cooperative asymmetric catalysis of chiral tetraaminophosphonium carboxylate (P,S)-1.OCOR has been established, and its synthetic utility has been successfully demonstrated by application to the highly enantioselective direct Mannich-type reaction of azlactones with N-sulfonyl imines. The present study stimulates the cultivation of the potential of the chiral quaternary onium salt catalysis by the structural modification of organic anion.

Cp2Ni-KOt-Bu-BEt3 (or PPh3) Catalyst System for Direct C−H Arylation of Benzene, Naphthalene, and Pyridine

Ni-catalyzed direct C-H arylation of benzene and naphthalene using aryl halides was investigated. For the first time, the arylation was successfully catalyzed by Cp(2)Ni (5 mol %) in the presence of KOt-Bu and BEt(3). This Ni catalyst system was also applied to direct C-H arylation of pyridine, an electron-deficient heteroarene; PPh(3) was used instead of BEt(3) in this case.

Chiral Ammonium Betaines: A Bifunctional Organic Base Catalyst for Asymmetric Mannich-Type Reaction of α-Nitrocarboxylates

A chiral ammonium betaine, an intramolecular ion-pairing quaternary ammonium aryloxide 3, has been designed and its vast potential as an enantioselective organic base catalyst has been successfully demonstrated in the highly enantioselective direct Mannich-type reaction of alpha-substituted alpha-nitrocarboxylates 2 with various N-Boc imines 1. The present study provides a conceptually new approach toward the design of bifunctional, chiral quaternary ammonium salts and their utilizations as a homogeneous organic molecular catalyst.

Highly Regio-, Diastereo-, and Enantioselective 1,6- and 1,8-Additions of Azlactones to Di- and Trienyl N-Acylpyrroles

A vinylog of Michael addition (1,6-addition) of azlactones to δ-substituted dienyl N-acylpyrroles has been developed with virtually complete 1,6-, diastereo-, and enantioselectivities by means of chiral P-spiro triaminoiminophosphorane as a catalyst. This system has been successfully extended to an unprecedented bis-vinylog of Michael addition (1,8-addition) of azlactones to ζ-substituted trienyl N-acylpyrroles with high levels of regio- and stereocontrol.

Generation of Chiral Phosphonium Dialkyl Phosphite as a Highly Reactive P-Nucleophile: Application to Asymmetric Hydrophosphonylation of Aldehydes

The generation of chiral tetraaminophosphonium dialkyl phosphite has been detected by low-temperature NMR analysis, and its synthetic potential as a remarkably reactive P-nucleophile has been successfully demonstrated by its application to the establishment of highly efficient and enantioselective hydrophosphonylation of various aldehydes. A systematic evaluation of the organic-base-dependent generation of the requisite ion pair and its reactivity and selectivity as a P-nucleophile reveals that the structure of the cationic conjugate acid of the base is a key element both for substantial generation of phosphite anions with prominent nucleophilicity and for rigorous stereocontrol. This study provides not only experimental demonstration of the importance of the phosphite tautomer in the P-C bond formation process but also a general yet valuable framework for the molecular design of even superior chiral organic base catalysts.

Synergistic Catalysis of Ionic Brønsted Acid and Photosensitizer for a Redox Neutral Asymmetric α-Coupling of N-Arylaminomethanes with Aldimines

A redox neutral, highly enantioselective coupling between N-arylaminomethanes and N-sulfonyl aldimines was developed by harnessing the efficient catalysis of P-spiro chiral arylaminophosphonium barfate and a transition-metal photosensitizer under visible light irradiation. This mode of synergistic catalysis provides a powerful strategy for controlling the bond-forming processes of reactive radical intermediates.

Chiral arylaminophosphonium barfates as a new class of charged brønsted acid for the enantioselective activation of nonionic Lewis bases.

Heterochiral [7.7]-P-spirocyclic arylaminophosphonium barfates have been designed as a novel charged, cationic Brønsted acid catalyst, and their catalytic and stereocontrolling abilities have been clearly demonstrated in the development of the unprecedented, highly enantioselective conjugate addition of arylamines to nitroolefins. This study uncovers a new function of chiral tetraaminophosphonium cations and its potential synthetic utility, thereby providing a new avenue to the molecular design of chiral charged Brønsted acid catalysts and their applications.

Base-Catalyzed Direct Aldolization of α-Alkyl-α-Hydroxy Trialkyl Phosphonoacetates

Catalytic direct aldol addition of α-hydroxy trialkyl phosphonacetates to aldehydes affords α-hydroxy-β-phosphonyloxy ester products. The fully substituted glycolate enolate intermediate is generated in situ under mild conditions via [1,2]-phosphonate-phosphate rearrangement. High enantioselectivity and dramatic enhancement of reaction diastereocontrol is realized via the application of chiral iminophosphorane catalysts. The phosphate products undergo stereoselective nucleophilic displacement reactions.

Catalytic Asymmetric Protonation of α-Amino Acid-Derived Ketene Disilyl Acetals Using P-Spiro Diaminodioxaphosphonium Barfates as Chiral Proton

Chiral diaminodioxaphosphonium salts have been developed and their unique abilities as a chiral proton have been revealed through the establishment of a highly enantioselective protonation of alpha-amino acid-derived ketene disilyl acetals.