Chengmei Huang

Direct CH Functionalization of Enamides and Enecarbamates by Using Visible‐Light Photoredox Catalysis

Direct C-H functionalization of various enamides and enecarbamates was realized through visible-light photoredox catalyzed reactions. Under the optimized conditions using [Ir(ppy)(2)(dtbbpy)PF(6)] as photocatalyst in combination with Na(2)HPO(4), enamides such as N-vinylpyrrolidinone could be easily functionalized by irradiation of the reaction mixture overnight in acetonitrile with visible light. The scope of the reaction with respect to enamide and enecarbamate substrates by using diethyl 2-bromomalonate for the alkylation reaction was explored, followed by an investigation of the scope of alkylating reagents used to react with the enamides and enecarbamates. The results indicated that reaction takes place with quite broad substrate scope, however, tertiary enamides with an internal C=C double bond in the E configuration could not be alkylated. Alkylation of N-vinyl tertiary enamides and enecarbamates gave monoalkylated products exclusively in the E configuration. Alkylation of N-vinyl secondary enamides gave doubly alkylated products. Double bond migration was observed in the reaction of electron-deficient bromides such as 3-bromoacetyl acetate with N-vinylpyrrolidinone. A mechanism is proposed for the reaction that is different from reported reactions of SOMOphiles with a nonfunctionalized C=C double bond. Further tests on the trifluoromethylation and arylation of enamides and enecarbamates under similar conditions showed that the reactions could serve as a mild, practical, and environmentally friendly approach to various functionalized enamides and enecarbamates.

Facile synthesis of spiroisoquinolines based on photocycloaddition of isoquinoline-1,3,4-trione with oxazoles

Photocycloaddition of isoquinoline-1,3,4-trione and 5-methoxyoxazoles affords spiroisoquinolineoxetanes with high regio- and diastereoselectivity. The spiroisoquinolineoxetanes can be conveniently converted into novel spiroisoquinolineoxazoline derivatives through acid catalyzed sequential reactions.

Small molecular inhibitors of miR-1 identified from photocycloadducts of acetylenes with 2-methoxy-1,4-naphthalenequinone.

Small molecules which can modulate endogenous microRNAs are important chemical tools to study microRNA regulational network. In this Letter we screened the [2+2] photocycloadducts of 2-methoxy-1,4-naphthalenequinone with a series of aryl acetylenes on their activity to modulate endogenous microRNAs. A potent inhibitor of the muscle-specific miR-1 which is closely related with cardiac development and disease was identified. The small molecular inhibitor was the cyclobutene type product derived from the photocycloaddition of 2-methoxy-1,4-naphthalenequinone with tert-butyl (5-(phenylethynyl)quinolin-8-yl) carbonate. Analogues of the small molecular inhibitor were then prepared using similar photocycloaddition reactions for evaluation on inhibition activity on miR-1 to provide structure-activity relationship of the miR-1 inhibitor.

Photocycloadditions of substituted oxazoles with isoquinoline-1,3,4-trione—chemo-, regio-, diastereoselectivities and transformation of the photocycloadducts

Photoreactions of isoquinoline-1,3,4-triones and oxazoles with different substituents were found to give different chemo-, regio- and diastereoselectivities. The substituent at the C5 on the oxazole ring showed great influence on the chemoselectivity of the photoreaction as well as on the transformation of the photocycloadducts. The 2-methyl-5-methoxyoxazoles reacted with isoquinoline-1,3,4-triones rapidly and gave spirooxetanes with high regio- and diastereo-selectivity. Diastereoselectivity in the reaction of 2-phenyl-5-methoxyoxazoles with isoquinoline-1,3,4-triones was relevant to the substituent on the 4-position on the oxazole ring. Replacement of the 5-methoxy group with 5-methyl or 5-phenyl resulted in significant decrease on the reactivity of the oxazole as well as change on the diastereoselectivity in photocycloaddition with isoquinoline-1,3,4-triones. Acid-mediated transformations of the photocycloadduct spirooxetanes was found to give different type of products including β-hydroxy-α-aminocarbonyl compounds and spiroisoquinolineoxazolines under different reaction conditions. Substituents on the spirooxetanes as well as the type and amount of acid used in the reaction played important roles in determining the type and diastereoselectivity of the products in the transformations.

Photo-Induced Cycloaddition Reactions of α-Diketones and Transformations of the Photocycloadducts

Photocycloaddition, along with subsequent transformation of the photocycloadducts, provides expeditious ways to construct various structures. The photo-induced reactions of α-diketones have been reported to proceed via different reaction pathways with the involvement of one or two of the carbonyl groups. Photoinduced reactions of cyclic α-diketones including N-acetylisatin, phenanthrenequinone and isoquinolinetrione with different C=C containing compounds could take place via [2 + 2], [4 + 2] or [4 + 4] photocycloaddition pathways. We have investigated the photoreactions of these cyclic α-diketones with different types of alkenes and alkynes, with a focus on the unusual cascade reactions initiated by the photocycloaddition reactions of these cyclic α-diketones and the applications of these photocycloaddition reactions along with the transformation of the photocycloadducts. In this paper, we discuss the diverse photo-cycloaddition pathways found in the photocycloaddition of o-diones leading to various photocycloadducts and the potential applications of these reactions via further transformation reactions of the adducts.

(1S*,4'S*,5R*)-1-Isopropyl-5-meth-oxy-2',3-dimethyl-4,6-dioxa-2-aza-spiro-[bicyclo-[3.2.0]hept-2-ene-7,4'-isoquinoline]-1',3'(2'H,4'H)-dione.

In the isoquinoline ring system of the title molecule, C18H20N2O5, the N-heterocyclic ring is in a half-boat conformation. The dioxa-2-azaspiro ring is essentially planar, with a maximum deviation of 0.029 (1) Å, and makes a dihedral angle of 30.63 (5)° with the benzene ring. The molecular structure is stabilized by a weak intramolecular C—H⋯O hydrogen bond, which generates a S(6) ring motif. In the crystal, molecules are linked via weak intermolecular C—H⋯O hydrogen bonds into a three-dimensional supramolecular network. Additional stabilization is provided by π–π stacking interactions between symmetry-related benzene rings with a centroid–centroid distance of 3.6507 (5) Å.

1-Benzyl-5-meth-oxy-2',3-dimethyl-4,6-dioxa-2-aza-spiro-[bicyclo-[3.2.0]hept-2-ene-7,4'-isoquinoline]-1',3'(2'H,4'H)-dione.

In the isoquinoline ring system of the title molecule, C22H20N2O5, the N-heterocyclic ring is in a half-boat conformation. The dioxa-2-azaspiro ring is essentially planar [maximum deviation = 0.026 (1) Å] and forms dihedral angles of 22.53 (5) and 64.46 (5)° with the benzene and phenyl rings, respectively. The molecular structure is stabilized by a weak intramolecular C—H⋯O hydrogen bond, which generates an S(7) ring motif. In the crystal, molecules are linked via weak intermolecular C—H⋯O and C—H⋯N hydrogen bonds into layers parallel to (102).

Acid-mediated transformation of spirocyclopropyl oxetanes: a facile approach to spirocyclopropyl butenolides and γ-butyrolactones

Spirocyclic oxetanes were found to undergo versatile transformations under different acid-mediated conditions. Treatment of spirocyclopropyl oxetanes with excess amounts of hydrochloric or hydrobromic acid at room temperature resulted in the formation of spirocyclopropyl fused butenolides with good yields. The transformation of spirocyclopropyl oxetanes mediated by hydroiodic acid led to spirocyclopropyl fused γ-butyrolactones instead of butenolides. Transformation of spirocyclopropyl oxetanes catalyzed by Lewis acid was also explored and found to give distinct products such as spirobutyl indolinones. The reaction mechanisms involved in the acid-mediated transformations were proposed.

5-Meth-oxy-1,2',3-trimethyl-4,6-dioxa-2-aza-spiro-[bicyclo-[3.2.0]hept-2-ene-7,4'-isoquinoline]-1',3'(2'H,4'H)-dione.

In the isoquinoline ring system of the title molecule, C16H16N2O5, the N-heterocyclic ring is in a half-boat conformation. The dioxaazaspiro ring is essentially planar [maximum deviation = 0.022 (1) Å] and forms a dihedral angle of 24.56 (4)° with the benzene ring.

Methyl 2,2′-dimethyl-4′-[2-(methyl­sulfan­yl)eth­yl]-1,3-dioxo-2,3-dihydro-1H,4′H-spiro­[isoquinoline-4,5′-oxazole]-4′-carboxyl­ate

In the isoquinoline ring system of the title molecule, C18H20N2O5S, the fused N-heterocyclic ring is distorted towards a half-boat conformation. The methyl formate moiety is disordered over two sets of sites with refined occupancies of 0.882 (5) and 0.118 (5). In the crystal, molecules are linked via weak intermolecular C—H⋯O hydrogen bonds into one-dimensional chains along [010].