Reaction of polyspirocyclic internal gem dibromocyclopropanes with methyllithium. An unusual carbenoid rearrangement

A skeletal rearrangement of a series of polyspiro internal gem dibromocyclopropanes in the presence of methyllithium reagents was studied. The rearranged products of two types were obtained: substituted bromocyclobutenes (type B ) and C-H insertion products (type K ) resulting from the reaction of the carbenoid intermediate H with the ether solvent. The mechanism of the carbenoid rearrangement is discussed.


Introduction
Earlier we have reported 1 the first example of a skeletal rearrangement of dibromospiranes of type A in the presence of methyllithium (Scheme 1, routes 1 and 2).In general, the reaction of dibromides A with methyllithium forms the corresponding allenes D as major products (Scheme 1, route 3).This transformation, so-called Doering-Scattebol-Moore reaction, is well documented. 2 It has been found that lowering the reaction temperature to -55 °C favors the formation of rearrangment products B and C and disfavors the formation of allenes D.

Scheme 1
In our recent work 4 we have systematically studied the reaction of a number of terminal gem dibromospiropentanes with methyllithium forming dimer rearrangement products of type C (Scheme 1) in good yields.We have also investigated the reaction of several dibromospiranes containing tetrasubstituted dibromocyclopropane moieties with methyllithium, and either monomer rearrangement products B or C-H insertion products were obtained.Carbenes, including cyclopropylidene, can form molecules resulting from intramolecular insertion into C-H bonds of the solvent.3c,5 In order to elucidate the mechanism a series of internal dibromospiropentanes have been studied in the reaction with methyllithium.

Results and Discussion
In the present work we explore the reaction of methyllithium with a series of gem dibromospiranes containing an internal gem dibromocyclopropane scaffold, with the goal to understand the influence of dibromocyclopropane substituents on the type of rearrangement products formed and to draw some conclusions about the mechanism of the rearrangement.

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The first group of compounds 1-3 contains the 7,7-dibromodispiro[2.1.0]heptanemoiety.Earlier, we have found that 1 reacts with methyllithium at -55 °C to produce mainly the monomer rearrangement product of type B (Scheme 1). 1 Repeating this reaction confirmed the formation of cyclobutene 8 in high yield (77%).The more substituted compound 2 reacted with methyllithium in the same manner yielding the rearranged product 9. Dibromide 2 contains two bonds a and b prone to migrate.The formation of product 9 indicates that this rearrangement proceeds with migration of bond a, i.e., ring-opening of the more substituted three-membered ring occurs.
A different result was obtained with the tetrasubstituted dibromospiropentane 3. Instead of a monomer product of type B (Scheme 1), the reaction with methyllithium at --55 °C resulted in the formation of allene 10 (product type D, Scheme 1).
The reaction of methyllithium with dibromospiropentanes 4-6 containing spirocyclies of larger ring sizes gave a different result: ethers 11-13 were formed in the course of the incorporation of the ether solvent molecule, likely via an intermediacy of a corresponding carbene and its insertion into C-H bond of ether.It has been reported 5b that treatment of dibromide 6 with methyllithium at -45 °C provides a mixture of eight products with compound 13 as the main product (40% yield).We reinvestigated this reaction at -55 °C and isolated exclusively the product 13 in high yield (89%).
Thus, depending on the size of the cyclic substituent in dibromides 1-6 two types of rearrangement products were obtained: monomer products 8 and 9 of type B (Scheme 1) from dibromides 1 and 2 containing cyclopropyl substituents, and solvent insertion products 11-14 in the case of dibromides 4-7 with alkyl or larger cycloalkyl substituents.Reaction paths for the formation of rearrangment products 8-14 are conceived as follows (Scheme 2): Presumably, the first step of the reaction of dibromospiranes A with methyllithium leads to the formation of lithium carbenoid E. Subsequently, nucleophilic attack of the C-C bond of the spiro-linked three-membered ring at the carbenoid center generates via sequence F and G the rearranged cyclobutylidene carbenoid H.The electrophilicity of carbenoids has been studied and thoroughly reviewed. 6

Scheme 2
Depending on the structure, carbenoid H may serve as intermediate for two ramified pathways (Scheme 2).One is the insertion reaction into the α-C-H bond of diethyl ether used as solvent affording products of type K.This insertion probably proceeds via the formation of the corresponding carbene, a substituted methylenecyclobutylidene.
The alternative transformation of carbenoid H is the [1,3]-sigmatropic migration of Li furnishing the lithium intermediate J followed by metal-halogen exchange and formation of the rearranged product of type B (Scheme 2).
In conclusion, we propose a mechanistic rationalization for the rearrangement, which allows to explain the competing processes.The main point of the suggested reaction paths (Scheme 2) is the concept of a carbocationic type of transformation of Li-carbenoid intermediates.Especially noteworthy is that carbenoids of the Li-C-Br type can react with such a weak nucleophile like a C-C bond.This process, which is still a rare case, represents the skeletal carbocationic-type rearrangements in carbenoids.

Reaction of substituted gem dibromospiropentanes 1-7 with methyllithium. General procedure
To a stirred solution of gem dibromospiropentanes 1-7 (3.3 mmol) in Et 2 O (10 mL) at -55 °C under argon was added dropwise over a period of 45 min methyllithium (2.75 mL of 1.6 M solution in Et 2 O, 4.4 mmol).After 1 h, the resulting mixture was allowed to slowly warm to 0 °C and was then quenched with cold water (20 mL).The aqueous layer was extracted with Et 2 O (3 × 10 mL), the organic layers were combined, dried over anhydrous MgSO 4 , and concentrated in vacuo.The crude products were purified by column chromatography (silica gel, petroleum ether).