Nickel-Catalyzed Organozinc-Promoted Carbocyclizations of Electron-Deficient Alkenes with Tethered Unsaturation

Abstract

A nickel-catalyzed method for cyclizations of electron-deficient alkenes with tethered unsaturation in the presence of organozincs was developed. Considerable flexibility in the structure of each reactive component was observed. Enones, alkylidene malonates, unsaturated β-ketoesters, and nitroalkenes participated as the electron-deficient alkene; alkynes, enones, 1,3-dienes, and aldehydes participated as the tethered unsaturation; and a variety of sp2 and sp3-hybridized organozincs, including those that possess β-hydrogens, participated as the nucleophilic component. Substrate structure, organozinc structure, and ligand structure all played a significant role in determining product selectivities. Of particular synthetic significance was the opportunity to prepare either E or Z tri- or tetrasubstituted alkenes from a common alkyne. A discussion of probable mechanisms is provided.

Cycloisomerization of 1,n‐Enynes: Challenging Metal‐Catalyzed Rearrangements and Mechanistic Insights

“…Various 1,n-enynes have been cyclized in the Scheme 46. Mechanism for the In-catalyzed skeletal reorganization of 1,6-enynes according to Equations (199) and (200). presence of several metals through different reaction pathways to give functionalized carbo-or heterocycles.…”

“…[199] a,b-Unsaturated enynes and an organozinc or aluminum derivative were found to participate, in general, in the coupling process. [200] Electrondeficient double bonds in combination with a terminal triple bond, as in 525, generally underwent efficient cyclization upon exposure to [Ni(cod) 2 ] and an organozinc compound (generated from MeLi and ZnCl 2 ) to give alkylidenecycloalkanes [Eq. (177)].…”

“…Substrate 589 is readily converted into allylcyclopentene 590 at 80 8C in dichloroethane in the presence of 10 mol % InCl 3 [Eq. (200)]. …”

Nickel‐Catalyzed Reductive Cyclizations and Couplings

“…An apparent requirement for the coupling or cyclization to proceed effectively is that the alkene unit must be electron deficient. Intramolecular versions of this process, largely developed in our laboratories, have been demonstrated with organozinc reagents (as in the production of 7 and 8), [13] organoaluminum reagents, [14] and alkenyl zirconium reagents (as in the production of 9, Scheme 4). [15] Both internal and terminal alkynes are cleanly tolerated as the acetylenic component, and enones, alkylidene malonates, nitroalkenes, and unsaturated imides are tolerated as the electron-deficient alkene component.…”

Nickel‐katalysierte reduktive Cyclisierungen und Kupplungen

“…Die Kupplung oder Cyclisierung verläuft allerdings nur glatt, wenn das Alken elektronenarm ist. Intramolekulare Varianten der Reaktion wurden von uns intensiv untersucht und mit Organozink-(wie bei der Synthese von 7 und 8), [13] Organoaluminium- [14] oder Alkenylzir- coniumreagentien (wie bei der Synthese von 9) ausgeführt (Schema 4). [15] [17] Wie die Synthese von 13 belegt, reagieren auch Alkylzinkverbindungen (in Reinform eingesetzt oder aus der entsprechenden Organolithiumverbindung und Zinkchlorid erhalten) glatt in Dreikomponenten-Kupplungen.…”