Modeling Selenoprotein Se-Nitrosation: Synthesis of a Se-Nitrososelenocysteine with Persistent Stability.

The Se-nitrosation in selenoproteins such as glutathione peroxidase and thioredoxin reductase to produce Se-nitrososelenocysteines (Sec-SeNOs) has been proposed to play crucial roles in signaling processes mediated by reactive nitrogen species and nitrosative-stress responses, although chemical evidence for the formation of Sec-SeNOs has been elusive not only in proteins but also in small-molecule systems. Herein, we report the first synthesis of a Sec-SeNO by employing a selenocysteine model system that bears a protective molecular cradle. The Sec-SeNO was characterized using 1H and 77Se nuclear magnetic resonance as well as ultraviolet/visible spectroscopy and found to have persistent stability at room temperature in solution. The reaction processes involving the Sec-SeNO provide experimental information that serves as a chemical basis for elucidating the reaction mechanisms involving the SeNO species in biological functions, as well as in selenol-catalyzed NO generation from S-nitrosothiols.

Highly Electrophilic Intermediates in the Bypass Mechanism of Glutathione Peroxidase: Synthesis, Reactivity, and Structures of Selenocysteine-Derived Cyclic Selenenyl Amides.

Selenocysteine (Sec)-derived cyclic selenenyl amides, formed by the intramolecular cyclization of Sec selenenic acids (Sec-SeOHs), have been postulated to function as protective forms in the bypass mechanism of glutathione peroxidase (GPx). However, their chemical properties have not been experimentally elucidated in proteins or small-molecule systems. Recently, we reported the first nuclear magnetic resonance observation of Sec-SeOHs and their cyclization to the corresponding cyclic selenenyl amides by using selenopeptide model systems incorporated in a molecular cradle. Herein, we elucidate the structures and reactivities of Sec-derived cyclic selenenyl amides. The crystal structures and reactions toward a cysteine thiol or a 1,3-diketone-type chemical probe indicated the highly electrophilic character of cyclic selenenyl amides. This suggests that they can serve not only as protective forms to suppress the inactivation of Sec-SeOHs in GPx but also as highly electrophilic intermediates in the reactions of selenoproteins.

Remote Electronic Effect of Chiral N-Heterocyclic Carbene Catalyst on an Asymmetric Benzoin Reaction.

A remote electronic effect of chiral aminoindanol-derived N-heterocyclic carbene catalyst on an asymmetric benzoin reaction was investigated. The catalyst bearing remote electron-withdrawing substituents increased enantioselectivity of the reaction at the cost of the reaction rate. DFT calculations rationalized the increased enantioselectivity.

Late-Stage Functionalization of the Periphery of Oligophenylene Dendrimers with Various Arene Units via Fourfold C-H Borylation.

Late-stage functionalization of the periphery of oligophenylene dendrimers was efficiently achieved via site-selective C-H activation of a preconstructed, readily accessible dendron. By fourfold iridium-catalyzed C-H borylation followed by Suzuki-Miyaura cross-coupling, various arene units were introduced into the end points of the 1,3,5-phenylene-based hydrocarbon dendron. Coupling of the modified dendrons with a core unit, such as 2,6-dibromobenzoic acid derivatives, afforded the periphery-functionalized dendrimers that also have an endohedral functionality at the core position.

Enantio- and diastereoselective double Mannich reaction of malononitrile with N-Boc imines using quinine-derived bifunctional organoiodine catalyst.

A chiral quinine-derived organic base catalyst with halogen bond donor functionality was used to catalyze the asymmetric double Mannich reaction of malononitrile with N-Boc and N-Cbz imines to afford 1,3-diamines in excellent yields with high enantio- and diastereoselectivities. With 2.2 equiv. of a single imine electrophile, symmetrical 1,3-diamines were obtained, whereas, with two different imine partners, unsymmetrically substituted 1,3-diamine was obtained. The monohydration of the double Mannich product was also achieved.

Chiral Benzazaborole-Catalyzed Regioselective Sulfonylation of Unprotected Carbohydrate Derivatives.

Chiral benzazaborole-catalyzed regioselective sulfonylations of unprotected carbohydrate derivatives have been developed. This methodology enables direct regioselective functionalization of the secondary OH group in carbohydrate in the presence of the primary OH group. By using the chiral organoboron catalysis, kinetic resolution of the carbohydrate derivatives was also achieved.

Chiral benzazaboroles as catalysts for enantioselective sulfonylation of cis-1,2-diols.

A newly developed benzazaborole smoothly catalyzed the enantioselective sulfonylation of cis-1,2-diols. Using a chiral benzazaborole/NMI co-catalyst system, various sulfonate esters were prepared in high yields with good enantioselectivities.

Catalysis Based on C-I⋠⋠⋠π Halogen Bonds: Electrophilic Activation of 2-Alkenylindoles by Cationic Halogen-Bond Donors for [4+2] Cycloadditions.

Homo- and cross-[4+2] cycloadditions of 2-alkenylindoles, catalyzed by cationic halogen-bond donors, were developed. Under mild reaction conditions, 3-indolyl-substituted tetrahydrocarbazole derivatives were obtained in good to excellent yields. Experimental and quantum calculation studies revealed that the electrophilic activation of 2-alkenylindoles was achieved by C-I⋅⋅⋅π halogen bonds.

Oxa- and Azacycle Formation via Migrative Cyclization of Sulfonylalkynol and Sulfonylalkynamide with N-Heterocyclic Carbene.

An N-heterocyclic carbene promotes cyclization of sulfonylalkynols and sulfonylalkynamides that accompanies 1,2-migration of the sulfonyl groups. This reaction provides a novel access to oxa- and azacycles possessing a pendent vinyl sulfone functionality, which, in turn, is amenable for further transformations.

Catalytic asymmetric [3 + 2]-cycloaddition for stereodivergent synthesis of chiral indolyl-pyrrolidines.

The stereochemical divergent synthesis of indolyl-pyrrolidines was accomplished using an imidazoline-aminophenol (IAP)-Ni(OAc)2 complex and a bis(imidazolidine)pyridine (PyBidine)-Cu(OTf)2 complex. The former catalyzed exo'-selective asymmetric [3 + 2] cyclization of iminoesters with indolyl nitroalkenes, and the latter catalyzed the reaction in an endo-selective manner. These catalysts are tolerant toward highly functional substrates that supply chiral indolyl-pyrrolidine hybrids.

Enhanced rate and selectivity by carboxylate salt as a basic cocatalyst in chiral N-heterocyclic carbene-catalyzed asymmetric acylation of secondary alcohols.

The rate and enantioselectivity of chiral NHC-catalyzed asymmetric acylation of alcohols with an adjacent H-bond donor functionality are remarkably enhanced in the presence of a carboxylate cocatalyst. The degree of the enhancement is correlated with the basicity of the carboxylate. With a cocatalyst and a newly developed electron-deficient chiral NHC, kinetic resolution and desymmetrization of cyclic diols and amino alcohols were achieved with extremely high selectivity (up to s = 218 and 99% ee, respectively) at a low catalyst loading (0.5 mol %). This asymmetric acylation is characterized by a unique preference for alcohols over amines, which are not converted into amides under the reaction conditions.

Remote electronic effect on the N-heterocyclic carbene-catalyzed asymmetric intramolecular Stetter reaction and structural revision of products.

The remote electronic effects of chiral N-heterocyclic carbene catalysts on the asymmetric intramolecular Stetter reaction are investigated. The reaction rate and enantioselectivity were markedly influenced by a substituent at a remote position of the catalyst. The absolute configurations of the products are revised on the basis of X-ray diffraction. Density-functional theory calculations rationalize the improvement of the enantioselectivity using an electron-deficient catalyst.

Chiral C2-Symmetric Aminomethylbinaphthol as Synergistic Catalyst for Asymmetric Epoxidation of Alkylidenemalononitriles: Easy Access to Chiral Spirooxindoles.

Chiral C2-symmetric 3,3'-bis((R,R)-2-naphthylethylaminomethyl)-(R)-binaphthol (AMB4) functions as an efficient organocatalyst for the asymmetric epoxidation of various alkylidenemalononitriles. The spiro-epoxyoxindole products obtained from isatilidenemalononitriles were easily transformed to the corresponding chiral dihydroquinoxalinyl spirooxindoles.

A Hypervalent Cyclic Dibenzoiodolium Salt as a Halogen-Bond-Donor Catalyst for the [4+2] Cycloaddition of 2-Alkenylindoles.

A stable, hypervalent cyclic dibenzoiodolium salt acted as a strong halogen bonding (XB)-donor catalyst for [4+2] cycloaddition of 2-alkenylindoles, and not as an oxidizing agent. The cross-[4+2] cycloaddition of 2-vinylindoles with 2-alkenylindoles was catalyzed smoothly by the hypervalent cyclic dibenzoiodolium triflate catalyst to give the tetrahydrocarbazoles in up to 99 % yield with 17 : 1 diastereoselectivity. The hypervalent cyclic dibenzoiodolium salt was also applicable to the Povarov reaction of 2-vinylindole with N-p-methoxyphenyl (PMP) imine to give the indolyl-tetrahydroquinoline in 83 % yield.

A chiral organic base catalyst with halogen-bonding-donor functionality: asymmetric Mannich reactions of malononitrile with N-Boc aldimines and ketimines.

A chiral organic base catalyst with halogen-bonding-donor functionality has been developed. This quinidine-derived acid/base catalyst smoothly promoted the asymmetric Mannich reaction of malononitrile and various N-Boc imines with up to 98% ee. The cooperative interaction with both substrates was responsible for the high activity that allowed a reduction of the catalyst amount to 0.5 mol%.

Site-selective benzoin-type cyclization of unsymmetrical dialdoses catalyzed by N-heterocyclic carbenes for divergent cyclitol synthesis.

A highly site-selective N-heterocyclic carbene (NHC)-catalyzed benzoin-type cyclization of unsymmetrical dialdoses is developed to enable a divergent cyclitol synthesis. The choice of chiral NHCs and protecting groups affects the site-selectivity. The resulting inososes are converted into epi-, muco- and myo-inositols, and their chiral protected derivatives are formed in good yields.

Chemoselective conversion of α-unbranched aldehydes to amides, esters, and carboxylic acids by NHC-catalysis.

Depending on the N-heterocyclic carbene catalyst utilized, α-unbranched aldehydes selectively provided amides, esters, or carboxylic acids through oxidation by NCS. The α-unbranched aldehyde underwent these reactions chemoselectively in the presence of an aromatic or α-branched aldehyde.