Activation of cyclopropanes by transition metals
In
Two main approaches achieve C-C bond activation using a transition metal. One strategy is to increase the ring strain and the other is to stabilize the resulting cleaved C-C bond complex (e.g. through aromatization or chelation). Because of the large ring strain energy of cyclopropanes (29.0 kcal per mole), they are often used as substrates for C-C activation through oxidative addition of a transition metal into one of the three C-C bonds leading to a metallacyclobutane intermediate.
Substituents on the cyclopropane affect the course of its activation.[3]
Reaction scope
Cyclopropane
The first example of cyclopropane being activated by a metal complex was reported in 1955, involving the reaction of cyclopropane and
The electrophile Cp*Ir(PMe3)(Me)OTf reacts with cyclopropane to give the allyl complex:[7]
- Cp*Ir(PMe3)(Me)OTf + C3H6 → [Cp*Ir(PMe3)(η3-C3H5)]OTf + CH4
Fused and spiro-cyclopropanes
Using the same rhodium(I) catalyst and C-C bond activation strategy one can access compounds with
Cyclopropyl halides
Nickel(0) complexes oxidatively cleave halocyclopropanes to give allyl)Ni(II) halides.[10]
Cyclopropylketones
With cyclopropylketones, transition metal can coordinate to the ketone to direct oxidative addition into the proximal C-C bond. The resulting metallacyclobutane intermediate can be in equilibrium with the six-membered alkyl metal enolate depending on presence of a Lewis acid (e.g. dimethylaluminum chloride[11]).
With the metallacyclobutane intermediate, 1,2-migratory insertion into an
Cyclopropylimines
Oxidative addition into cyclopropylimines gives a metalloenamine intermediate similar to oxidative addition to cyclopropylketones giving alkylmetalloenolates. These intermediates can also reaction with alpha-beta unsaturated ketones to give disubstituted cyclopentane products following reductive elimination.[16]
With rhodium, the intermediate metalloenamine reacts with tethered alkynes.[17] and alkenes[18] to give cyclized products such as pyrroles and cyclohexenones, respectively.
Alylidenecyclopropanes
Alkylidenecyclopropanes more readily undergo C-C bond oxidative addition than cyclopropanes.
Following oxidative addition, 1,2-insertion mechanisms are common and reductive elimination yields the desired product. The 1,2-insertion step usually occurs with an alkyne,[19] alkene,[20] or allene[21] and the final product is often a 5 or 7 membered ring. Six-membered rings may be formed after dimerization of the metallocyclobutane intermediate with another alkylidenecyclopropane substrate and subsequent reductive elimination.[22] Common transition metals utilized with alkylidenecyclopropanes are nickel, rhodium, and palladium. It has been shown that the metallacyclobutane intermediate following oxidative addition to the distal C-C bond can isomerize.[23]
Vinylcyclopropanes
Oxidative addition of vinylcyclopropanes primarily occurs at the proximal position, giving pi-allyl intermediates. Through subsequent insertion reactions (e.g. with alkynes,[24] alkenes,[25] and carbon monoxide[26]), rings of various sizes and fused ring systems[27] can be formed.
Cyclopropenes
Oxidative addition into cyclopropenes normally occurs at the less hindered position to yield the metallacyclobutane. This reaction can result in formation of cyclopentadienones,[28] cyclohexenones,[29] and phenols.[29]
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