Nickel-Catalyzed Regioselective Intermolecular Dialkylation of Alkenylarenes: Generation of Two Vicinal C(sp )-C(sp ) Bonds Across Alkenes.

We disclose a Ni-catalyzed regioselective dialkylation reaction of alkenylarenes with α-halocarbonyls and alkylzinc reagents. The reaction produces γ-arylated alkanecarbonyl compounds with the generation of two new C(sp )-C(sp ) bonds at the vicinal carbons of alkenes. This reaction is effective for the use of primary, secondary and tertiary α-halocarboxylic esters, amides and ketones in conjunction with primary and secondary alkylzinc reagents as the sources of two C(sp ) carbons for the dialkylation of terminal and cyclic internal alkenes.

Cu-Catalyzed Cyclization/Coupling of Alkenyl Aldimines with Arylzinc Reagents: Access to Indole-3-diarylmethanes.

We report a Cu(II)-catalyzed cyclization/coupling of alkenyl aldimines with arylzinc reagents to create indole-3-diarylmethane derivatives (Sapkota et al. , DOI: 10.26434/chemrxiv-2022-d6qn).

Ni-Catalyzed Regio- and Stereoselective Alkylarylation of Unactivated Alkenes in γ,δ-Alkenylketimines.

We disclose a Ni-catalyzed vicinal alkylarylation of unactivated alkenes in γ,δ-alkenylketimines with aryl halides and alkylzinc reagents. The reaction produces γ-C(sp)-branched δ-arylketones with the construction of two new C(sp)-C(sp) and C(sp)-C(sp) bonds. Electron-deficient alkenes play crucial dual roles as ligands to stabilize reaction intermediates and to increase catalytic rates for the formation of C(sp)-C(sp) bonds.

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

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.

Nickel-Catalyzed Regioselective Alkenylarylation of γ,δ-Alkenyl Ketones via Carbonyl Coordination.

We disclose a nickel-catalyzed reaction, which enabled us to difunctionalize unactivated γ,δ-alkenes in ketones with alkenyl triflates and arylboronic esters. The reaction was made feasible by the use of 5-chloro-8-hydroxyquinoline as a ligand along with NiBr ⋅DME as a catalyst and LiOtBu as base. The reaction proceeded with a wide range of cyclic, acyclic, endocyclic and exocyclic alkenyl ketones, and electron-rich and electron-deficient arylboronate esters.

Walking metals: catalytic difunctionalization of alkenes at nonclassical sites.

Migration of metals along a carbon chain is triggered by two of the most common organometallic elementary steps - β-hydride (β-H) elimination and alkene hydrometallation. This process heralds a new future for creating bonds at carbon sites that fall outside the tenets of the conventional wisdom for reactivity and bond formation, and provides an opportunity to leverage β-H elimination to advance the very reaction of alkene difunctionalization it is intrinsically predestined to disrupt. Almost four decades since its genesis, the early adventure for alkene difunctionalization by metal migration was sporadic, and its later development went on a hiatus primarily due to original impetus on arresting β-H elimination for vicinal alkene difunctionalization.

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

An Expedient Route to 9-arylmethylanthracene Derivatives via Tandem Ni-catalyzed Alkene Dicarbofunctionalization and Acid-promoted Cyclization-aromatization.

We report a nickel-catalyzed one pot synthesis of 9-arylmethylanthracene motifs, which find applications in medicinal and material chemistry. In this synthesis, we apply three component alkene dicarbofunctionalization of 2-vinylaldimines with aryl iodides and arylzinc reagent to generate a 1,1,2-diarylethyl scaffold, which then undergoes an acidpromoted cyclization followed by aromatization to furnish 9-arylmethylanthracene cores. With the new method, a number of differently-substituted 9-arylmethylanthracene derivatives can be synthesized in good yields.

Design, synthesis, and evaluation of cystargolide-based β-lactones as potent proteasome inhibitors.

The peptidic β-lactone proteasome inhibitors (PIs) cystargolides A and B were used to conduct structure-activity relationship (SAR) studies in order to assess their anticancer potential. A total of 24 different analogs were designed, synthesized and evaluated for proteasome inhibition, for cytotoxicity towards several cancer cell lines, and for their ability to enter intact cells. X-ray crystallographic analysis and subunit selectivity was used to determine the specific subunit binding associated with the structural modification of the β-lactone (P), peptidic core, (P and P), and end-cap (P) of our scaffold.

A total synthesis of (-)-Hortonone C.

A total synthesis of the cytotoxic terpenoid hortonone C was accomplished and its absolute stereochemistry confirmed. Intermediate (+)- was synthesized using either an asymmetric conjugate addition strategy, or by elaboration of the Hajos-Parrish ketone. Reduction of (+)- under dissolving-metal conditions and trapping the enolate intermediate served to control the cis-stereochemistry at the ring fusion and provide a silyl enol ether necessary for ring expansion.

Total synthesis and absolute stereochemistry of the proteasome inhibitors cystargolides A and B.

The absolute stereochemistry of the cystargolides was determined by total synthesis. Evaluation of synthetic cystargolides and derivatives showed that the natural (2S,3R) stereochemistry is essential for activity. Moreover, benzyl esters (-)-10 and (-)-15 were found to be about 100 times more potent, and to selectively kill MCF-7 cancerous cells.