Shin Kamijo

Photochemically induced radical transformation of C(sp3)-H bonds to C(sp3)-CN bonds.

A general protocol for direct transformation of unreactive C(sp(3))-H bonds to C(sp(3))-CN bonds has been developed. The C-H activation was effected by photoexcited benzophenone, and the generated carbon radical was subsequently trapped with tosyl cyanide to afford the corresponding nitrile in a highly efficient manner. The present methodology is widely applicable to versatile starting materials and, thus, serves as a powerful tool for selective one-carbon elongation for construction of architecturally complex molecules.

Radical amination of C(sp3)-H bonds using N-hydroxyphthalimide and dialkyl azodicarboxylate.

A direct conversion of C(sp(3))-H bonds to C(sp(3))-N bonds has been achieved by utilizing catalytic N-hydroxyphthalimide (NHPI) and stoichiometric dialkyl azodicarboxylate. NHPI functions as a precursor of the electron-deficient phthalimide N-oxyl radical (PINO) to abstract hydrogens, and dialkyl azodicarboxylate acts as a trapping agent of the resultant carbon radical to generate the hydrazine derivatives. This C-H amination proceeds in a highly chemoselective manner with a wide applicability to functionalize benzylic, propargylic, and aliphatic C-H bonds. Furthermore, the obtained hydrazine compounds were readily converted to the corresponding carbamates or amines. Hence, the present protocol for direct introduction of the nitrogen functionality serves as a powerful tool for efficient construction of nitrogen-substituted natural products and pharmaceuticals.

Regiospecific synthesis of 2-allyl-1,2,3-triazoles by palladium-catalyzed 1,3-dipolar cycloaddition

2-Allyl-1,2,3-triazoles were prepared by the palladium-catalyzed three component coupling (TCC) reaction of alkynes, allyl methyl carbonate and trimethylsilyl azide. A π-allylpalladium azide complex, which undergoes the 1,3-dipolar cycloaddition with alkynes, is proposed as a key intermediate in the TCC reaction.

Photochemically induced radical alkenylation of C(sp3)–H bonds

The direct alkenylation of C(sp3)–H bonds was achieved by employing benzophenone and 1,2-bis(phenylsulfonyl)ethylene under photo-irradiation conditions. This simple metal-free reaction enables the substitution of heteroatom-substituted methine, methylene and aliphatic C(sp3)–H bonds by (E)-sulfonylalkene units in a highly chemoselective manner. The derived sulfonylalkenes were further converted in a single step to the prenyl derivatives via a second photo-induced radical substitution and to the pyrrole derivatives via cyclization and aromatization steps. The present protocol thus serves as an efficient method for the direct extension of carbon skeletons for the synthesis of structurally complex natural products and pharmaceuticals.

Palladium catalyzed intramolecular hydrocarbonation of allenes leading to carbocycles

Abstract The intramolecular hydrocarbonation of certain allenes ( 1 and 3 ), bearing active methyne groups at the terminus of the carbon chain, proceeded smoothly in the presence of catalytic amounts of palladium complex ([( η 3 -C 3 H 5 )PdCl] 2 -dppf) to give the corresponding carbocycles ( 2 and 4 , respectively) in good to high yields.

Synthesis of 5-substituted 1H-tetrazoles by the copper-catalyzed [3+2] cycloaddition of nitriles and trimethylsilyl azide.

The copper-catalyzed [3+2] cycloaddition between various nitriles and trimethylsilyl azide in DMF/MeOH produced the corresponding 5-substituted 1H-tetrazoles in good to high yields. It was proposed that the reaction proceeds through the formation in situ of a copper azide species and subsequent [3+2] cycloaddition with the nitriles. Furthermore, we found that a copper and triethylamine combined catalyst also promoted the cycloaddition of nitriles and trimethylsilyl azide to afford the 5-substituted 1H-tetrazoles at relatively low reaction temperatures. The copper azide species would be formed by reaction of the copper catalyst with Et(3)NHN(3) generated in situ.

Palladium catalyzed hydrosulfination of allenes with tosylhydrazine leading to allylsulfones

Abstract The palladium catalyzed reaction of allenes 1 with tosylhydrazine in the presence of 1 equiv AcOH and 10 mol% dppf gave the corresponding allylsufones 2 in moderate to good yields.

Ring Opening of Cyclic Vinylogous Acyl Triflates Using Stabilized Carbanion Nucleophiles: Claisen Condensation Linked to Carbon−Carbon Bond Cleavage

Addition of stabilized carbanionic nucleophiles to cyclic vinylogous acyl triflates (VATs) triggers a ring-opening fragmentation to give acyclic beta-keto ester and related products, much like those observed traditionally in the Claisen condensation. Unlike in the classical Claisen condensation, however, the VAT-Claisen reaction described herein is rendered irreversible by C-C bond cleavage, not by deprotonation of the activated methylene product. Full details of this original reaction methodology are disclosed herein, including how subtle differences between the various nucleophiles impact the proper choice of reaction conditions for making 1,3-diketones, beta-keto esters, and beta-keto phosphonates.

Synthesis of cyclic ethers via the palladium catalyzed intramolecular hydrocarbonation of alkoxyallenes

Abstract The intramolecular hydrocarbonation of certain alkoxyallenes (1, 3 and 5), bearing active methine groups at the terminus of the carbon chain, proceeded smoothly in the presence of catalytic amounts of a palladium complex [Pd(OAc)2-dppb] to give 5- to 7-membered cyclic ethers (2, 4 and 6, respectively) in good to high yields.

Direct Construction of 1,3-Diaxial Diol Derivatives by C−H Hydroxylation

Direct hydroxylation of tertiary C-H bonds for construction of 1,3-diaxial diol derivatives was achieved by devising a new detachable dioxirane precursor containing a trifluoromethyl ketone moiety and ethylene tether. Oxone treatment of the ketones led to the corresponding dioxiranes, enabling hydroxy group installment into cyclohexane and steroid derivatives in a regio- and stereoselective manner through intramolecular oxygen insertion.