Unidirectional growth of organic single crystals of naphthalene, anthracene and pyrene by isothermal expansion of supercritical CO2.

Unidirectional single crystals without grain boundaries are highly important in optoelectronic applications. Conventional methods to obtain such crystals involve organic solvents or seed crystals, which have numerous drawbacks. We present here a supercritical CO2-mediated method of the single crystal formation of naphthalene, anthracene and pyrene on the (001) plane without using seed crystals. Single dominant peaks in powder XRD (PXRD) with low full width at half maxima (FWHM) are described. The dependency of crystal size on the rate of depressurization was measured by precise and isothermal expansion of scCO2 solutions. The experimental setup is illustrated for continuous preparation without emission of CO2 or discharge of material into the environment. The materials are shown to be fully converted into crystals indicating a rapid, scalable and environmentally benign process of single crystal formation with practically nil E factor.

Cooperative Pd/Cu Catalysis to Spiro[indoline-2,3'-pyrrolidin]-2'-ones: Tandem Benzylation of α-Isocyano Lactams, Amine Addition, and N-Arylation.

A tandem three-component reaction has been developed for the synthesis of spirocyclic 2-indolinylformamidines through a cooperative action of palladium and copper catalysts. The Pd-catalyzed benzylation of α-isocyano lactams with 2-bromobenzyl bromides allows efficient formation of α-substituted α-isocyano lactams. A subsequent in situ Cu-catalyzed amine addition to the isocyanide moiety provides amidine intermediates that readily undergo intramolecular N-arylation via the cooperative action of Pd/Cu catalysis, allowing a facile chiral resolution of the spirocyclic 2-indolines.

Three-Component Reactions to Spirocyclic Pyrrolidinonylformimidamides: α-Isocyano Lactams as Two-Atom Unit in Silver-Catalyzed Formal [3 + 2] Cycloaddition Reactions.

A facile approach to spirocyclic pyrrolidinonylformimidamides has been developed via three-component reactions of isocyanides, alkenes, and amines. The reaction proceeds through a sequence of two distinct reaction pathways; the base-catalyzed conjugate addition of α-isocyano lactams to electron-deficient alkenes and the Ag(I)-catalyzed amine insertion to the isocyanide moiety. Both reactions display markedly different reaction kinetics, allowing the one-pot three-component reactions to be performed in the presence of respective catalysts, a Brønsted base and a silver salt. The formation of spirocyclic pyrrolidin-2-ones represents an unusual use of α-isocyano lactam as a two-atom unit in a formal [3 + 2] cycloaddition reaction. The successful identification of ways to defy the typical three-atom unit role of α-isocyano carbonyl compounds in the [3 + 2] cycloaddition pathways manifests a rapid assembly of medicinally important spirocyclic scaffolds from readily available starting materials.

Silver-Catalyzed Asymmetric Desymmetrization of Cyclopentenediones via [3 + 2] Cycloaddition with α-Substituted Isocyanoacetates.

A highly selective and practical asymmetric Ag(I) catalyst system has been developed for the [3 + 2] cycloaddition reactions between isocyanoacetates and cyclopentenediones. The current Ag(I) catalyst system tolerates moisture and air and readily utilizes class III solvents such as EtOAc and acetone. The development of on demand generation of an active chiral catalyst in the presence of isocyanides paves a way to the efficient asymmetric preparation of bicyclic pyrrolidines with four stereogenic centers, including two quaternary centers in 80-97% ee.

Substituted Pyrrololactams via Ring Expansion of Spiro-2H-pyrroles from Intermolecular Alkyne-Isocyanide Click Reactions.

The facile synthesis of 6- to 8-membered pyrrololactams has been developed using a ring expansion of spiro-2H-pyrroles, the products of intermolecular alkyne-isocyanide click reactions. The key to successful ring expansion of spiro-2H-pyrroles to pyrrololactams is the enforced orbital overlap between the internal alkene and the amide carbonyl group through the conformationally locked bicyclic structures. The newly disclosed α-isocyano lactams, substrates for click reactions, should find their utility in the synthesis of pharmaceutically important heterocyclic compounds.

First example of quinine-squaramide catalyzed enantioselective addition of diphenyl phosphite to ketimines derived from isatins.

A highly enantioselective addition of diphenyl phosphite to ketimines derived from isatins has been achieved using a bifunctional organocatalyst, quinine-derived squaramide catalyst. This method works efficiently with several ketimines to produce the corresponding 3-amino-2-oxoindolin-3-yl-phosphonates in excellent yields with high enantioselectivity (up to 98% ee).

Enantioselective Friedel-Crafts alkylation of indoles with 2-enoylpyridine-N-oxides catalyzed by glucoBOX-Cu(II) complex.

The glucosamine derived glucoBOX-Cu(II) complex was found to be a unique catalytic system for enantioselective Friedel-Crafts alkylation of indoles with 2-enoylpyridine-1-oxides. A large number of 3-alkylated indole derivatives were prepared using 5 mol% glucoBOX-Cu(II) complex in excellent yields with high enantioselectivity up to 99% ee.