[3 + 3] Cyclodimerization of Methylenecyclopropanes: Stoichiometric and Catalytic Reactions of Nickel(0) with Electron-Deficient Alkylidenecyclopropanes

Abstract

Stoichiometric treatment of Ni(cod) 2 with ethyl cyclopropylideneacetate (ECPA) in the presence of PCy 3 resulted in an unpredicted formation of a Ni(0) complex bearing an (E,E)-1,2-bis(exo-alkylidene)cyclohexane ligand, which stemmed from the [3 þ 3] cyclodimerization of ECPA. The reaction could be expanded to a Ni(0)-catalyzed [3 þ 3] cyclodimerization reaction of ester-substituted methylenecyclopropanes, giving the corresponding cyclohexane derivatives in excellent yields.Methylenecyclopropanes (MCPs) are strained reactive molecules, and transition-metal-catalyzed cyclodimerization or cycloaddition reactions of MCPs have provided an atomefficient, powerful strategy for the synthesis of a variety of cyclic compounds. 1 Nickel(0) is also known to catalyze cyclodimerization reactions of MCPs to afford cyclobutane and cyclopentane derivatives via [2 þ 2] and [3 þ 2] cyclodimerizations, respectively (Chart 1). 2-4 Pioneering work on the cyclodimerization of methylenecyclopropane in the presence of Ni(cod) 2 , giving a mixture of dispiro[2.1.2.1]octane ([2 þ 2] product) and 5-methylenespiro[2.4]heptane ([3 þ 2] product), was reported by Binger. 2a The usage of maleic anhydride as an additive with the Ni(0) catalyst was found to be effective for the selective formation of the [3 þ 2] cyclodimerization product, 2c whereas the introduction of tertiary phosphines into the Ni(0) catalytic system resulted in the preferential formation of MCP trimers. 2b Interestingly, employing dialkyl fumarates as the solvent in the Ni-catalyzed reaction was devised to give another dimer, 1,3-dimethylenecyclohexane, as a minor product. 2c The selective [3 þ 2] cyclodimerization of methylenecyclopropane, on the other hand, was also caused by treating with Pd(0) catalyst. 3 In contrast, the limiting studies of cyclodimerization reactions of substituted MCPs have been described thus far: the cyclodimerization of 1-methylene-2-vinylcyclopropane with Pd(0) catalysts was reported by Binger, 4a and the reaction of ethyl cyclopropylideneacetates in the presence of Ni catalysts was developed by Saito. 4b Although a number of the cyclodimerizations of MCPs have been reported as described above, there is a very limiting example for [3 þ 3] cyclodimerization in which two proximal C-C bonds are cleaved (Chart 1). 4b In these related reactions, some attempts to confirm the reaction intermediates have been made. Based on the isolation and characterization of a nickelacyclopentane intermediate (Chart 1, A) by using (bipy)Ni(cod) as a Ni (0) precursor, oxidative cyclization of methylenecyclopropane with Ni(0) has been regarded as a key reaction step. 5 The C-C bond cleavage of the cyclopropane ring could be achieved via β-carbon elimination of A, which is known as a "cyclopropyl-butenyl rearrangement", during the catalytic reaction. Another possibility was proposed that the oxidative addition of a proximal bond to Ni(0) took place at the initial stage of the reaction to give 2-methylene-1-nickelacyclobutane (Chart 1, B), while the corresponding interm...

Nickel-Catalyzed Ring-Opening Three-Component Coupling of Methylenecyclopropane with Aldehydes and Silanes

“…First, oxidative addition of the proximal C−C bond of methylenecyclopropane 1 to nickel(0) affords 2-alkylidene-1-nickelacyclobutane intermediate A . The formation of a 2-alkylidene-1-nickelacyclobutane complex from the nickel(0) complex system by reaction with methylenecyclopropane has been proposed previously. ,, Next, the Ni−C bond of intermediate A undergoes insertion into aldehyde 2 to give intermediate B . In addition to this mechanism, the formation of metallacycle C , followed by ring-opening is also possible .…”

(3 + 3)-Cyclodimerization of Donor–Acceptor Cyclopropanes. Three Routes to Six-Membered Rings

“…In general, there are three types of species that can participate in (3 + n )-cyclodimerizations: (1) 1,3-dipoles, (2) 1,3-biradicals, and (3) three-membered rings. Thus, (3 + 2)-cyclodimerization of nitrile oxides is a preparative method of furoxans synthesis. , There are also scarce examples of other (3 + 2)-cyclodimerizations, − among which the most important is a formation of cyclopentanes from the corresponding cyclopropane derivatives. , Alternatively, (3 + 3)-cyclodimerizations have been reported for various 1,3-dipoles including nitrile oxides, , carbonyl oxides, − carbonyl imides, nitrile imides, , carbonyl ylides, thiocarbonyl ylides, − azomethine ylides, etc. , (3 + 3)-Cyclodimerization has also been reported for 1,3-biradicals, such as trimethylenemethanes; however, this reaction usually proceeds with low yields and is accompanied by formation of various side products. − Additionally, there are limited reports of (3 + 3)-cyclodimerization for three-membered heterocycles (oxiranes, − dioxiranes, thiiranes, , thiirenes, aziridines, , and azirines − ), which can be considered as precursors of the corresponding 1,3-dipoles.…”

“…The (3 + 3)-cyclodimerization of three-membered carbocycles is an almost unexplored field except for nickel-catalyzed dimerizations of methylenecyclopropanes. , Meanwhile, there is a special class of cyclopropanes, namely donor–acceptor (D–A) cyclopropanes, which appear to be very appropriate as candidates for (3 + 3)-cyclodimerization. − They are considered to be well-proven synthetic equivalents of a three-carbon 1,3-zwitterionic synthon of I type (Scheme ) possessing a dual nature and showing both 1,3-dipole-like − and dipolarophile-like − properties. However, to date there have not been any reports where these two types of reactivity of D–A cyclopropanes were combined in one reaction proceeding as (3 + 3)-cyclodimerization and leading to the cyclohexane formation ( I+I path, Scheme ).…”

Cycloaddition of Fluorenone N-Aryl Nitrones with Methylenecyclopropanes and Sequential 1,3-Rearrangement: An Entry to Synthesis of Spirofluorenylpiperidin-4-ones

“…The methylenecyclopropane 2d , 2e , 2f , 2g , 2h , 2i , 2j , and 2k were prepared according to literature methods, and their spectral data matched literature values.…”