Ni-Catalyzed Regioselective Reductive 1,3-Dialkenylation of Alkenes.

Dicarbofunctionalization is an important efficient synthetic technique for adding two chemical moieties across an alkene. Here, a novel method of reductive dicarbofunctionalization has been developed using a single alkenyl triflate as the electrophile, combined with an unactivated alkene. The reaction does not require an external auxiliary and proceeds with complete regioselectivity.

Ni-Catalyzed Arylbenzylation of Alkenylarenes: Kinetic Studies Reveal Autocatalysis by ZnX2 *.

We report a Ni-catalyzed regioselective arylbenzylation of alkenylarenes with benzyl halides and arylzinc reagents. The reaction furnishes differently substituted 1,1,3-triarylpropyl structures that are reminiscent of the cores of oligoresveratrol natural products. The reaction is also compatible for the coupling of internal alkenes, secondary benzyl halides and variously substituted arylzinc reagents. Kinetic studies reveal that the reaction proceeds with a rate-limiting single-electron-transfer process and is autocatalyzed by in-situ-generated ZnX2 . The reaction rate is amplified by a factor of three through autocatalysis upon addition of ZnX2 .

Transition Metal (Ni, Cu, Pd)-Catalyzed Alkene Dicarbofunctionalization Reactions.

Recently, alkene dicarbofunctionalization, i.e., the powerful organic synthesis method of alkene difunctionalization with two carbon sources, emerged as a formidable reaction with immense promise to synthesize complex molecules expeditiously from simple chemicals. This reaction is generally achieved with transition metals (TMs) through interception by carbon sources of an alkylmetal [ß-H-C(sp3)-[M]] species, a key intermediate prone to undergo rapid ß-H elimination. Related prior reports, since Paolo Chiusoli and Catellani's work in 1982 [ Tetrahedron Lett. 1982, 23, 4517], have used bicyclic and disubstituted terminal alkenes, wherein ß-H elimination is avoided by geometric restriction or complete lack of ß-H's. With reasoning that ß-H-C(sp3)-[M] intermediates could be rendered amenable to interception with the use of first row late TMs and formation of coordination-assisted transient metallacycles, these two strategies were implemented to address the ß-H elimination problem in alkene dicarbofunctionalization reactions.Because first row late TMs catalyze C(sp3)-C(sp3) coupling, Cu and Ni were anticipated to impart sufficient stability to ß-H-C(sp3)-[M] intermediates, generated catalytically upon alkene carbometalation, for their subsequent interception by carbon electrophiles/nucleophiles in three-component reactions. Additionally, such an innate property could enable alkene difunctionalization with carbon coupling partners through entropically driven cyclization/coupling reactions. The cyclometalation concept to stabilize intractable ß-H-C(sp3)-[M] intermediates was hypothesized when three-component reactions were performed. The idea of cyclometalation to curtail ß-H elimination is founded upon Whitesides's [ J. Am. Chem. Soc. 1976, 98, 6521] observation that metallacycles undergo ß-H elimination much slower than acyclic alkylmetals.In this Account, examples of alkene dicarbofunctionalization reactions demonstrate that Cu and Ni catalysts could enable cyclization/coupling of alkenylzinc reagents, alkyl halides, and aryl halides to afford complex carbo- and heterocycles. In addition, forming coordination-assisted transient nickellacycles enabled regioselective performance of three-component dicarbofunctionalization of various alkenyl compounds. In situ reaction of [M]-H with alkenes generated after ß-H elimination induced an unprecedented metallacycle contraction process, in which six-membered metal-containing rings shrank to five-membered cycles, allowing creation of new carbon-carbon bonds at allylic (1,3) positions. Applications of these regioselective alkene dicarbofunctionalization reactions are discussed.

Ni-Catalyzed Regioselective 1,2-Dialkylation of Alkenes Enabled by the Formation of Two C(sp3)-C(sp3) Bonds.

We disclose a Ni-catalyzed vicinal difunctionalization of alkenes with benzyl halides and alkylzinc reagents, which produces products with two new alkyl-alkyl bonds. This alkene dialkylation is effective in combining secondary benzyl halides and secondary alkylzinc reagents with internal alkenes, which furnishes products with three contiguous all-carbon secondary stereocenters. The products can be readily elaborated to access complex tetralene, benzosuberene, and bicyclodecene cores. The reaction also features as the most efficient alkene difunctionalization process to date with catalyst loadings down to 500 ppm and the catalytic turnover number (TON) and turnover frequency (TOF) registering up to 2 × 103 and 165 h-1 at rt, respectively.

Crystal structure of a fluorescent C-shaped molecule containing closely stacked bithiophene-substituted quinoxaline rings.

Molecules with well-defined structures that feature closely stacked aromatic rings are important for understanding π-π interactions. A previously reported C-shaped molecule with bithiophene-substituted quinoxaline rings suspended from an aliphatic bridge that holds the aromatic rings in close proximity exists as a pair of syn and anti diastereomers. The anti isomer, namely (1α,2ß,4ß,5α,16α,17ß,19ß,20α)-1,5,16,20-tetrachloro-31,31,32,32-tetramethoxy-11,26-bis[5-(thiophen-2-yl)thiophen-2-yl]-7,14,22,29-tetraazanonacyclo[18.10.1.15,16.02,19.04,17.06,15.08,13.021,30.023,28]dotriaconta-6(15),7,9,11,13,21(30),22,24,26,28-decaene chloroform monosolvate, C48H36Cl4N4O4S4·CHCl3, whose X-ray structure is described herein, has cofacial quinoxaline rings with bithiophene rings attached on opposite sides. The molecular structure is approximately C-shaped and consists of an aliphatic spacer with a boat-shaped cyclohexane ring in the middle. The centroid-to-centroid distance between the quinoxaline rings is 3.950 (1) Å, with ring-offset distances of 0.354 (3) and 0.816 (2) Å. The pendant bithiophene rings are oriented parallel to one another, which results from the thiophene rings connected to the quinoxaline rings being oriented such that their S atoms are rotated inward toward one another, but are not overlapped. Intermolecular packing is largely governed by van der Waals forces and a few weak C-H...X (X = N or O) interactions.