p-Diarylboryl Halothiophenols as Multifunctional Catalysts via Photoactive Intramolecular Frustrated Lewis Pairs.

p-Diarylboryl halothiophenols are developed and unequivocally characterized. Their photophysical properties and catalytic performance are unveiled by experimental and theoretical investigations. This novel class of triarylboranes behaves as a Brønsted acid to generate the corresponding borylthiophenolate that can absorb visible light to undergo intramolecular charge transfer to form a radical pair consisting of a boron radical anion and thiyl radical, which acts as a single-electron reductant while engaging in hydrogen atom transfer to regenerate the parent borylthiophenol. The synthetic relevance of this mode of action is demonstrated by the establishment of unique catalysis that integrates three different yet tunable functions in a single catalytic cycle, thereby allowing borylthiophenols to solely promote the assembly of sterically congested 1,2-diols and 1,2-aminoalcohol derivatives via radical-radical cross-coupling.

Zwitterionic Acridinium Amidate: A Nitrogen-Centered Radical Catalyst for Photoinduced Direct Hydrogen Atom Transfer.

The development of small organic molecules that can convert light energy into chemical energy to directly promote molecular transformation is of fundamental importance in chemical science. Herein, we report a zwitterionic acridinium amidate as a catalyst for the direct functionalization of aliphatic C-H bonds. This organic zwitterion absorbs visible light to generate the corresponding amidyl radical in the form of excited-state triplet diradical with prominent reactivity for hydrogen atom transfer to facilitate C-H alkylation with a high turnover number. The experimental and theoretical investigations revealed that the noncovalent interactions between the anionic amidate nitrogen and a pertinent hydrogen-bond donor, such as hexafluoroisopropanol, are crucial for ensuring the efficient generation of catalytically active species, thereby fully eliciting the distinct reactivity of the acridinium amidate as a photoinduced direct hydrogen atom transfer catalyst.

Zwitterionic Diphenylphosphinyl Amidate as a Powerful Photoinduced Hydrogen-Atom-Transfer Catalyst for C-H Alkylation of Simple Alkanes.

The chemical and physical properties of amides change substantially when the electron-withdrawing groups attached to the nitrogen are varied. Herein, we report the superior performance of N-diphenylphosphinyl 1,2,3-triazolium amidate as a photoinduced hydrogen-atom transfer catalyst compared to its N-benzoyl analog. A binary catalyst system of the phosphinyl amidate and an Ir-based photocatalyst enables the alkylation of unbiased C-H bonds.

Catalytic Asymmetric Cyanoalkylation of Electron-Deficient Olefins with Potassium Cyanide and Alkyl Halides.

The stereoselective cyanoalkylation of electron-deficient olefins with potassium cyanide and alkyl halides was developed based on the utilization of modular chiral 1,2,3-triazolium salts featuring a hydrogen bond-donor ability as catalysts. The reaction involving multiple carbon-carbon bond formations proceeds via the enantioselective conjugate addition of a cyanide ion and the consecutive catalyst-controlled diastereoselective alkylation of intermediary chiral triazolium enolates. Control experiments revealed that the use of a properly tuned chiral triazolium ion as a catalyst and the presence of the cyano functionality in the intermediary enolate are of crucial importance for achieving high levels of acyclic absolute and relative stereocontrol.

Exploiting Transient Radical Cations as Brønsted Acids for Allylic C-H Heteroarylation of Enol Silyl Ethers.

Intermediary radical cations, generated through single-electron oxidation of enol silyl ethers by excited Ir-based photocatalysts, can be exploited as Brønsted acids for the activation of heteroarylcyanides. This strategy enables the direct allylic C-H heteroarylation of enol silyl ethers under visible-light irradiation.

Catalytic asymmetric synthesis of 5-membered alicyclic α-quaternary ß-amino acids via [3 + 2]-photocycloaddition of α-substituted acrylates.

The photocatalytically active salt of a cationic iridium polypyridyl complex and a chiral borate is competent to promote a highly stereoselective [3 + 2]-cycloaddition of cyclopropylurea with α-substituted acrylates. This protocol provides straightforward access to a variety of stereochemically defined 5-membered alicyclic α-quaternary ß-amino acids, useful building blocks of ß-peptides and peptidomimetics.

Mannich-type allylic C-H functionalization of enol silyl ethers under photoredox-thiol hybrid catalysis.

The synergy of an Ir-based photosensitizer with mild oxidizing ability and a thiol catalyst enables efficient allylic C-H functionalization of enol silyl ethers with imines under visible light irradiation. Subsequent transformations of the aminoalkylated enol silyl ethers allow for the facile construction of unique molecular frameworks such as functionalized octahydroisoindol-4-one.

Urea as a Redox-Active Directing Group under Asymmetric Photocatalysis of Iridium-Chiral Borate Ion Pairs.

The development of a photoinduced, highly diastereo- and enantioselective [3 + 2]-cycloaddition of N-cyclopropylurea with α-alkylstyrenes is reported. This asymmetric radical cycloaddition relies on the strategic placement of urea on cyclopropylamine as a redox-active directing group (DG) with anion-binding ability and the use of an ion pair, comprising an iridium polypyridyl complex and a weakly coordinating chiral borate ion, as a photocatalyst. The structure of the anion component of the catalyst governs reactivity, and pertinent structural modification of the borate ion enables high levels of catalytic activity and stereocontrol. This system tolerates a range of α-alkylstyrenes and hence offers rapid access to various aminocyclopentanes with contiguous tertiary and quaternary stereocenters, as the urea DG is readily removable.

A Structurally Robust Chiral Borate Ion: Molecular Design, Synthesis, and Asymmetric Catalysis.

Catalysis by chiral weakly-coordinating anions (WCAs) remains underdeveloped due to the lack of a molecular design strategy for exploiting their characteristics, such as the non-nucleophilic nature. Here, we report the development of a chiral borate ion comprising an O,N,N,O-tetradentate backbone, which ensures hitherto unattainable structural robustness. Upon pairing with a proton, the hydrogen borate acts as an effective catalyst for the asymmetric Prins-type cyclization of vinyl ethers, providing access to structurally and stereochemically defined dihydropyrans. The key to selectivity control is the distinct ability of the borate ion to discriminate the prochiral faces of the acyclic oxonium ion intermediate and dictate the regiochemical outcome. We anticipate that this study paves the way for exploring the untapped potential of WCA catalysis for selective chemical synthesis.

Unveiling Latent Photoreactivity of Imines.

Unlike carbonyl compounds, it has long been common understanding that excited imines show virtually no photoreactivity, and hence their properties and potential utility in chemical science remain largely unexplored. Now, a strategy is presented for eliciting latent photoreactivity of imines based on the introduction of a donor-acceptor (D-A) structure to extend the lifetime of their photoexcited states. A series of spectroscopic analyses and density functional theory calculations reveal unique photophysical properties of the D-A-type imines. Furthermore, the reactivity of the D-A-type imines is demonstrated by using them as a photoredox catalyst for atom-transfer radical addition. These findings illuminate a previously neglected chemical space in the field of photochemistry, which will be exploited by taking advantage of the inherent structural modularity of imines.

Inserting Nitrogen: An Effective Concept To Create Nonplanar and Stimuli-Responsive Perylene Bisimide Analogues.

Establishing design principles to create nonplanar π-conjugated molecules is crucial for the development of novel functional materials. Herein, we describe the synthesis and properties of dinaphtho[1,8-bc:1',8'-ef]azepine bisimides (DNABIs). Their molecular design is conceptually based on the insertion of a nitrogen atom into a perylene bisimide core. We have synthesized several DNABI derivatives with a hydrogen atom, a primary alkyl group, or an aryl group on the central nitrogen atom. These DNABIs exhibit nonplanar conformations, flexible structural changes, and ambipolar redox activity. The steric effect around the central nitrogen atom substantially affects the overall structures and results in two different conformations: a nonsymmetric bent conformation and a symmetric twisted conformation, accompanied by a drastic change in electronic properties. Notably, the nonsymmetric DNABI undergoes unique structural changes in response to the application of an external electric field, which is due to molecular motions that are accompanied by an orientational fluctuation of the dipole moment. Furthermore, the addition of a chiral Brønsted base to N-unsubstituted DNABI affords control over the helical chirality via hydrogen-bonding interactions.

Catalyst-Directed Guidance of Sulfur-Substituted Enediolates to Stereoselective Carbon-Carbon Bond Formation with Aldehydes.

A highly chemo-, regio-, and stereoselective glycolate aldol reaction of sulfur-substituted enediolates with aldehydes was developed by employing a l-cyclohexylglycine-derived chiral iminophosphorane as a catalyst. The key for establishing this protocol is the distinct ability of the iminophosphorane catalyst to precisely direct the equilibrium mixture of the enediolates toward the intermolecular carbon-carbon bond formation with simultaneous yet rigorous control of relative and absolute stereochemistry. The critical importance of the cyclohexyl substituents on the catalyst backbone in dictating the reaction pathway and the stereochemical outcome was elucidated through an extensive quantum analysis by density functional theory calculations.

Molecular Design, Synthesis, and Asymmetric Catalysis of a Hexacoordinated Chiral Phosphate Ion.

We describe the design, synthesis, and characterization of a chiral hexacoordinated phosphate ion that features an octahedral P(V) core consisting of two N,N,O-tridentate backbones. We further demonstrate that the corresponding hydrogen phosphate acts as an effective catalyst for a highly enantioselective Pictet-Spengler-type reaction, wherein the relationship between the structure of the chiral phosphate ion and its ability to dictate the absolute stereochemistry is revealed in conjunction with precise structural elucidation of the phosphate ion.

Catalyst-Enabled Site-Divergent Stereoselective Michael Reactions: Overriding Intrinsic Reactivity of Enynyl Carbonyl Acceptors.

A site-divergent stereoselective Michael reaction system is developed based on the identification of two distinct catalysts. Cinchonidine-derived thiourea catalyzes the 1,4-addition of prochiral azlactone enolates to enynyl N-acyl pyrazoles in a highly diastereo- and enantioselective manner to give stereochemically defined alkynes, while P-spiro chiral triaminoiminophosphorane catalytically controls the stereoselective 1,6-addition and the consecutive γ-protonation of the vinylogous enolate intermediate to afford Z,E-configured conjugated dienes. This 1,6-adduct serves as a valuable precursor for the synthesis of a 2-amino-2-deoxy sugar.

Origin of High Regio-, Diastereo-, and Enantioselectivities in 1,6-Addition of Azlactones to Dienyl N-Acylpyrroles: A Computational Study.

Chiral P-spiro triaminoiminophosphorane (1) was developed to promote the highly regio-, diastereo-, and enantioselective 1,6- and 1,8-additions of azlactones (2·H) to dienyl and trienyl N-acylpyrroles (3 and 4). DFT calculations enabled us to gain deep insight into the whole reaction mechanism as well as the origin of the high regio- and stereoselectivities. The present reaction consists of three steps: (1) formation of the phosphonium-enolate ion-pair complex by deprotonation of 2·H with 1, (2) C-C bond formation of 2 with 3 and 4, and (3) protonation of the resulting enolate anion. The C-C bond formation is irreversible, and the rate- and stereodetermining step. The Cα-protonation preferentially proceeds rather than the thermodynamically and kinetically disfavored O- and Cγ-protonation, respectively. The high regio- and enantioselectivities are mainly attributed to the steric and electronic features of 1·H and 3/4. The hydrogen bonds (NH-O and CH-O) and the attractive CH-π interaction between 1·H and 2 and 3 play a key role in achieving high stereocontrol. The high regioselectivity is mainly controlled by the structural distortion of 1·H and the disruption of the π-conjugated system of 3 (1,4-system) and 4 (1,4- and 1,6-systems).

Site-Selective Conjugate Addition Through Catalytic Generation of Ion-Pairing Intermediates.

Site-selectivity in conjugate addition reactions is tightly associated with the principle of vinylogy. Various vinylogous nucleophiles and electrophiles have been applied to stereoselective conjugate additions directed by chiral small-molecule catalysts. This chapter focuses on the systems that control site- and stereoselectivity via chiral ion-pairing intermediates under organocatalytic conditions and describes individual vinylogous substrates in a separate section. Although site-selectivity originates largely from the intrinsic stereoelectronic nature of individual substrates, catalyst-controlled site-selectivity can be attained in certain cases.

Independence from the Sequence of Single-Electron Transfer of Photoredox Process in Redox-Neutral Asymmetric Bond-Forming Reaction.

A catalytic cycle initiated by the oxidative quenching of the excited photosensitizer (Ir*(ppy)3) is established for the enantioselective coupling between (N-arylamino)methanes and (N-methanesulfonyl)aldimines catalyzed by Ir-based photosensitizer and a chiral (arylamino)phosphonium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate under visible light irradiation. This achievement clearly demonstrates the insensitivity of this redox-neutral asymmetric reaction to the sequence of the key redox events involved in the synergistic catalysis.

Chiral ammonium betaine-catalyzed asymmetric Mannich-type reaction of oxindoles.

A highly diastereo- and enantioselective Mannich-type reaction of 3-aryloxindoles with N-Boc aldimines was achieved under the catalysis of axially chiral ammonium betaines. This catalytic method provides a new tool for the construction of consecutive quaternary and tertiary stereogenic carbon centers on biologically intriguing molecular frameworks with high fidelity.

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.