Catalytic reductive [4 + 1]-cycloadditions of vinylidenes and dienes

Abstract

Cycloaddition reactions provide direct and convergent routes to cycloalkanes, making them valuable targets for the development of synthetic methods. Whereas six-membered rings are readily accessible from Diels-Alder reactions, cycloadditions that generate five-membered rings are comparatively limited in scope. Here, we report that dinickel complexes catalyze [4 + 1]-cycloaddition reactions of 1,3-dienes. The C₁ partner is a vinylidene equivalent generated from the reductive activation of a 1,1-dichloroalkene in the presence of stoichiometric zinc. Intermolecular and intramolecular variants of the reaction are described, and high levels of asymmetric induction are achieved in the intramolecular cycloadditions using a C ₂-symmetric chiral ligand that stabilizes a metal-metal bond.

Fig. 1.. Reaction development.

(A) Complementary cycloaddition routes to five- and six-membered rings from 1,3-dienes. (B) Pericyclic [4 + 1]-cycloadditions suffer from large electronic barriers due to repulsion between the carbene lone pair and the Ψ₁ orbital of the 1,3-diene. (C) A dinickel-catalyzed reductive [4 + 1]-cycloaddition of 1,1-dichloroalkenes and 1,3-dienes. NMP, N-methyl-2-pyrrolidone; rt, room temperature.

Fig. 2.. Reaction scope.

Reactions were conducted on a 0.2 mmol scale, and isolated yields were determined following purification. Standard reaction conditions: 1,1-dichloroalkene (1.0 equiv), 1,3-diene (2.0 to 3.0 equiv), Zn (3.0 equiv), Ni(dme)Br₂ (10 to 20 mol%), L4 (5 to 10 mol%). See Supplementary material for experimental details. *Using catalyst 3. †Using Ni(dme)Br₂/L10.

Fig. 3.. Synthetic applications of the catalytic [4 + 1]-cycloaddition reaction.

A [4 + 1]-Cycloaddition approaches to the synthesis of cyclopentenones, stereodefined cyclopentanes, and cyclopentadienyl metal complexes. B Chiral dinickel catalyst using a C₂-symmetric ligand. C Intramolecular and asymmetric [4 + 1]-cycloaddition reactions (reaction times: 12 to 24 h; reaction temperatures: rt to 50 °C).

Fig. 4.. Mechanistic investigations.

A Distinguishing between direct [4 + 1]-cycloaddition and tandem [2 + 1]-cycloaddition/1,3-rearrangement mechanisms. B Stoichiometric [4 + 1]-cycloaddition using an isolable low-valent [NDI]Ni₂Cl complex. C Proposed catalytic mechanism. D DFT models for the stepwise migratory insertion–reductive elimination pathway. Energies are relative to that of 66, and all structures are fully optimized at the M06-L/6–31G(d,p) level of DFT (S = 1/2 spin state).