Daishi Fujino

Synthesis of 3-Trifluoromethylbenzo[b]furans from Phenols via Direct Ortho Functionalization by Extended Pummerer Reaction

A concise and diversity-oriented route to trifluoromethylbenzo[b]furans has been devised. A variety of phenols are directly converted to the corresponding 2-methylthio-3-trifluoromethylbenzo[b]furans by new triflic-anhydride-mediated extended Pummerer annulation reactions with trifluoromethylketene dithioacetal monoxide. The methylthio group of the products undergoes further transformations, which increase the diversity of available trifluoromethylbenzo[b]furans.

Regiocontrolled Palladium-Catalyzed Arylative Cyclizations of Alkynols

Tuning the reactivity of arylpalladium intermediates enables control of catalytic arylative 5-exo and 6-endo cyclizations of alkynols. The two modes of cyclizations represent a rare example of controllable, regioselective difunctionalization of alkynes. The cyclizations are useful in offering a divergent synthesis of oxygen-containing heterocycles, which is of synthetic use for further derivatization. Formal synthesis of an hNK-1 receptor antagonist also showcases the utility of our arylative cyclization.

Synthesis of alkylidenecyclopropanes by palladium-catalyzed reaction of propargyl-substituted malonate esters with aryl halides by anti-carbopalladation pathway.

Palladium-catalyzed arylative cyclization of propargyl-substituted malonate esters with aryl halides offers a stereoselective approach to alkylidenecyclopropanes. The reaction proceeds by an anti-carbopalladation pathway, which guarantees the exclusive stereocontrol of the resulting double bond. The highly strained as well as densely substituted skeletons of the products facilitate further versatile transformations, which underscores the importance of the products as synthetic intermediates.

Palladium-Catalyzed Cross-Coupling of Unactivated Aryl Sulfides with Arylzinc Reagents under Mild Conditions

Cross-coupling of general aryl alkyl sulfides with arylzinc reagents proceeds smoothly, even at room temperature or below, with a palladium-N-heterocyclic carbene (NHC) catalyst. When combined with reactions that are unique to organosulfurs, that is, the SNAr sulfanylation or Pummerer reaction, the cross-coupling offers interesting transformations that are otherwise difficult to achieve. An alkylsulfanyl group is preferentially converted whilst leaving the tosyloxy and chloro intact, which expands the variety of orthogonal cross-coupling.

Synthesis of 1,2-disubstituted cyclopentenes by palladium-catalyzed reaction of homopropargyl-substituted dicarbonyl compounds with organic halides via 5-endo-dig cyclization.

Palladium catalysts with bulky biaryl phosphine ligands allow homopropargyl-substituted dicarbonyl compounds to undergo intramolecular addition via a rare 5-endo-dig pathway. C-C bond forming reductive elimination follows the addition to introduce alkenyl and alkynyl as well as aryl groups by using the corresponding organic halides. The cyclization is versatile enough to be applicable to the synthesis of highly substituted dihydropyrrole and a fused tricyclic compound.

Palladium-catalyzed allylation of aryl halides with homoallyl alcohols bearing a trisubstituted double bond: application to chirality transfer from hydroxylated carbon to benzylic one.

A facile route to homoallyl alcohols bearing a trisubstituted double bond has been devised. The palladium-catalyzed reactions of aryl halides with the alcohols thus synthesized result in regiospecific allyl transfer from the alcohols to aryl halides via retro-allylation, providing allylarenes having two substituents at the 1 and 2 positions of the allyl moiety. Optically active homoallyl alcohols transfer their chirality at the hydroxylated carbon to the benzylic carbon of the product.

TIPS‐TTF as a Precursor of Low‐Symmetry TTF Derivatives: Steric Protection Strategy in the Regioselective CH Modification of TTF

Triisopropylsilyltetrathiafulvalene (TIPS-TTF) has been devised as a promising platform for the synthesis of low-symmetry TTF derivatives. The bulky TIPS group allows TIPS-TTF to undergo palladium-catalyzed direct diarylation as well as LDA-mediated dilithiation exclusively on the roomier dithiole ring. Subsequent fluoride-mediated protodesilylation provided vicinally difunctionalized TTF, which could undergo further functionalization.

Intermolecular Reductive Radical Addition to 2-(2,2,2-Trifluoroethylidene)-1,3-dithiane 1-Oxide: Experimental and Theoretical Studies

Tin hydride mediated radical addition of organic halide to 2-(2,2,2-trifluoroethylidene)-1,3-dithiane 1-oxide has been devised. The reaction is equivalent to an unrealizable radical addition to trifluoromethylketene, providing useful α-trifluoromethyl carbonyl equivalents. The trifluoromethyl and the sulfoxide groups of the substrate play key roles for the success of the radical addition, lowering the barrier of the radical addition step and controlling the stereoselectivity of the reaction, which DFT calculations have elucidated.

Palladium-Catalyzed Intramolecular Carboacetoxylation of 4-Pentenyl-Substituted Malonate Esters with Iodobenzene Diacetate

Palladium-catalyzed difuntionalization reactions of alkenes are rapidly emerging as useful tools for synthesizing a diverse range of complex molecules from rather simple alkenes. Among them, oxidative processes involving a Pd/ Pd cycle have attracted increasing attention recently owing to their high efficiency as well as their mechanistic interest (Scheme 1). Reactions that oxidatively introduce two heter-