Kyalo Stephen Kanyiva

A strategy for C-H activation of pyridines: direct C-2 selective alkenylation of pyridines by nickel/Lewis acid catalysis.

The C-2 selective alkenylation of pyridine derivatives is achieved with a catalyst consisting of nickel and Lewis acid. Use of diorganozinc compounds as the Lewis acid catalyst gives C-2 monoalkenylation products, whereas AlMe3 changes the reaction course to afford C-2 dienylated products, which are derived from double insertion of alkynes into the C(2)−H bond. The reaction demonstrates a broad substrate scope and proceeds with high chemo-, regio-, and stereoselectivities under mild conditions compared with previous examples of direct C−H functionalization of pyridines.

Nickel-catalyzed alkenylation and alkylation of fluoroarenes via activation of C-H bond over C-F bond

Nickel/P(c-C(5)H(9))(3) (PCyp(3)) catalyst effects the addition reactions of fluoroarenes across alkynes, 1,3-dienes, and vinylarenes via the activation of C-H bonds over C-F bonds. The acidic C-H bonds located ortho to fluorine are exclusively activated to afford a range of alkenylated and alkylated fluoroarenes.

Direct Alkenylation and Alkylation of Pyridone Derivatives by Ni/AlMe3 Catalysis

Regioselective alkenylation and alkylation of 2-pyridone derivatives are achieved through inter- and intramolecular insertion of alkynes, 1,3-dienes, and alkenes into the C(6)-H bond by nickel/AlMe(3) catalysis. Coordination of the heterocycles to the Lewis acid cocatalyst through their basic carbonyl oxygen is considered to be responsible for the regioselective activation of the C-H bonds, probably through oxidative addition to nickel(0).

Nickel‐Catalyzed Hydroheteroarylation of Vinylarenes

reaction can be initiated by oxidative addition of aromatic C H bonds to a metal catalyst, before hydrometalation and reductive elimination. However, to the best of our knowledge, there is only a single report of this mechanism affording 1,1diarylethane compounds, with 1,2-diarylethanes being generally obtained as the major products from this mechanistic pathway. Another type of hydroarylation reaction of vinylarenes involves the Friedel–Crafts-type alkylation of arenes, wherein a metal catalyst acts as a Lewis acid to activate the double bond of vinylarenes. Although 1,1-diarylethanes are generally obtained from this reaction with good to excellent regioselectivity, the scope of arenes that can participate in this mechanism is severely limited to highly electron-rich arenes, including indoles that contain an electron-donating substituent and a few furan and thiophene derivatives. On the other hand, we recently reported that a nickel/tricyclopentylphosphine (PCyp3) catalyst effects the hydroarylation of 2-vinylnaphthalene with a highly electron-poor arene, pentafluorobenzene. Subsequent studies on the mechanism of the alkyne hydrofluoroarylation by the same nickel catalyst revealed that the catalysis was initiated by oxidative addition of the C H bonds of fluoroarenes to nickel(0). These studies prompted us to examine the hydroarylation of vinylarenes that contain relatively electron-poor heteroarenes. These compounds also undergo addition across alkynes, possibly through oxidative addition of C H bonds to nickel(0). Herein, we report the hydroheteroarylation of vinylarenes to give 1,1-diarylalkanes that contain a variety of heteroaryl groups. First, we examined the reaction of methyl 1-methylindole3-carboxylate (1a) with styrene (2a) in the presence of a nickel catalyst that was derived from [Ni(cod)2] (5–10 mol%) and a ligand (Table 1). We found that the use of 1,3-

Hydrocarbamoylation of Unsaturated Bonds by Nickel/Lewis-Acid Catalysis

Formamides are found to undergo addition reactions across alkynes and 1,3-dienes by nickel/Lewis acid catalysis to give a variety of alpha,beta- and beta,gamma-unsaturated amides with stereo- and regioselectivity. Intramolecular insertion reactions of olefins into the C-H bonds of formamides also proceed under similar conditions. The presence of Lewis acid cocatalysts is crucial, and formamide coordination to the Lewis acid is considered to be responsible for the activation of their formyl C-H bonds probably through oxidative addition to nickel(0).

Palladium-Catalyzed Direct C–H Silylation and Germanylation of Benzamides and Carboxamides

A palladium-catalyzed regioselective activation of C(sp(2))-H and C(sp(3))-H bonds of benzamides and carboxamides, followed by coupling with disilanes to afford organosilanes in moderate to high yields, with the aid of 8-aminoquinoline as a directing group, is reported. Catalytic C(sp(2))-H germanylation of benzamides also proceeds under the same palladium catalysis. The reaction tolerates a wide variety of functional groups and is scalable without yield reduction. The bidentate directing group is readily removed and recovered by the reaction with a hydrazine, with concominant generation of an acyl hydrazide.

Hydrofluoroarylation of alkynes with fluoroarenes

A combination of Ni(cod)(2) and PCyp(3) is found to be an effective catalyst for chemoselective activation of the C-H bond of fluoroarenes over C-F bonds followed by insertion of alkynes to allow direct alkenylation of the electron-deficient arenes. The characteristics of the reactions are: a C-H bond ortho to a fluorine substituent is selectively activated; the reactivity of fluorobenzenes is roughly proportional to the number of fluorine atoms. The reaction conditions tolerate a broad range of both alkynes and fluoroarenes containing both electron-withdrawing and -donating groups, thus allowing efficient synthesis of a variety of substituted ethenes containing a fluoroaryl motif in high regio- and stereoselective manners. Mechanistic studies including both labeling experiments and stoichiometric reactions reveal that oxidative addition of C-H bonds in fluoroarenes to nickel(0) is kinetically highly facile whereas that of C-F bonds is thermodynamically favoured.

Facile Two-Step Synthesis of 1,10-Phenanthroline-Derived Polyaza[7]helicenes with High Fluorescence and CPL Efficiency

A facile two-step synthesis of aza[7]helicenes possessing a 6-5-6-6-6-5-6 skeleton from commercially available 2,9-dichloro-1,10-phenanthroline via double amination with aniline derivatives followed by hypervalent iodine reagent-mediated intramolecular double-NH/CH couplings was developed. Single-crystal X-ray analyses of the helicenes revealed unique structures, including both a significantly twisted center and planar terminals of the skeleton. The azahelicenes show high fluorescent quantum yields (Φs) under both neutral (Φ: 0.25-0.55) and acidic conditions (Φ: up to 0.80). An enantiomerically pure aza[7]helicene showed high circularly polarized luminescence (CPL) activity under both neutral and acidic conditions (glum : up to 0.009).

Practical approach for hydroheteroarylation of alkynes using bench-stable catalyst

A simple and convenient method for hydroheteroarylation of alkynes using air- stable catalyst precursors is described. The addition of a solution of AlMe 3 in hexane to Ni(acac) 2 and tri(cyclopentyl)phosphonium tetrafluoroborate ([Cyp 3 PH)BF 4 ) rapidly generates an active Ni(0)/Cyp 3 P catalyst for cis-hydroheteroarylation of alkynes under mild conditions. The catalytic reaction is applicable to a wide range of heteroarenes to give heteroaryl-substituted ethenes in excellent stereo- and regioselectivities.

Total Synthesis of cis‐Clavicipitic Acid from Asparagine via Ir‐Catalyzed CH bond Activation as a Key Step

4-Substituted tryptophan derivatives and the total synthesis of cis-clavicipitic acid were achieved in reactions in which Ir-catalyzed C-H bond activation was a key step. The starting material for these reactions is asparagine, which is a cheap natural amino acid. The reductive amination step from the 4-substituted tryptophan derivative gave cis-clavicipitic acid with perfect diastereoselectivity.