Vinylcyclopropanes metal-catalyzed cycloadditions

In this chapter we provide an overview of studies originating from the above work and directed at the design and development of three new metal-catalyzed cycloaddition reactions, namely the [5+2] cycloaddition of vinylcyclopropanes (VCPs) and rc-systems, the [6+2] cycloaddition of vinylcyclobutanones and re-systems, and the three-component, [5+2+1] cycloaddition of VCPs, rc-systems, and CO. These new reactions provide fundamentally new approaches to a range of problems in seven- and eight-membered ring synthesis. 

Alkenes, Rh-catalyzed hydroformylations, 7, 249 Alkene-vinylcyclobutanone, in [6+2]-cycloadditions, 10, 624 Alkene-vinylcyclopropanes, metal-catalyzed [5+21-... 

Alkyne-vinylcyclopropanes, metal-catalyzed [5+23-cycloadditions, 10, 605 Alkynides, with tungsten carbonyls, 5, 666 Alkynoic acids, stannylmetallation, 9, 374 Alkynoles, hydration-dehydration reactions, 6, 841... 

Abstract Transition metal-catalyzed cycloadditions of cyclopropanes have been well developed over the past several decades, leading to numerous new types of cycloadditions which are complementary to the traditional cycloadditions for the synthesis of carbocycles. Cycloadditions of vinylcyclopropanes (VCPs) and methylenecyclopropanes (MCPs) constitute two main aspects of this field. VCPs can act either as five-carbon synthons or three-carbon synthons, depending on whether the vinyl substituent is acting as an additional two-carbon synthon or not. As five-carbon synthons, VCPs are involved in [5-1-1], [5-1-2], [5-I-2-1-1], and [5+1+2-I-1] cycloadditions. As three-carbon synthons, VCPs are mainly involved in [3-1-2] and [3-1-2-t-l] cycloadditions. MCPs mostly act as three-carbon synthons and can have [3-1-2] cycloadditions with different jt systems. Other types of cycloadditions involving MCPs are also reviewed, such as [3-rl], [3+2+2], and [4+3+2] cycloadditions. CycloadditirMis of some other unusual cyclopropane derivatives are also introduced briefly. The cycloadditions of VCPs and MCPs have found applications in total synthesis and some representative molecules are tabulated as selected examples. 

The first examples of transition metal-catalyzed [5 + 2]-cycloadditions between vinylcyclopropanes (VCPs) and 7r-systems were reported in 1995 by Wender and co-workers.10 This [5 + 2]-reaction was based conceptually on the Diels-Alder reaction, replacing the four-carbon, four-7r-electron diene with a five-carbon, four-electron VCP (Scheme 1). Although the [5 + 2]-reaction of VCPs and 7r-systems can be thought of as a homolog of the Diels-Alder [4 +21-reaction, the kinetic stability of VCPs (activation barrier for the thermal isomerization of VCP to cyclopentene has been reported as 51.7 kcal mol-1)11 makes the thermal [5 + 2]-reactions involving VCPs and 7r-systems very difficult to achieve. A report of a thermal [5 + 2]-cycloaddition between maleic anhydride and a VCP has been published,12 but this reaction has not been reproduced by others.13 14 Based on the metal-catalyzed isomerization of VCPs to cyclopentenes and dienes,15-20 Wender and co-workers hypothesized that a metal might be used to convert a VCP to a metallocyclohexene which in turn might be trapped by a 7r-system to produce a [5 + 2]-cycloadduct. Based on its previous effectiveness in catalyzed [4 + 2]-21 and [4 + 4]-cycloadditions (Section 10.13.2.4), nickel(0) was initially selected to explore the potential of VCPs as four-electron, five-carbon components in [5 + 2]-cycloadditions. 

Transition metal-catalyzed higher-order cycloadditions offer a powerful approach for the constmction of medium-sized rings [1]. In this context, Wender and co-work-ers have developed catalytic cycloadditions of vinylcyclopropanes with alkynes,... 

A further possibility exists for employing substituted cyclopropane substrates in metal-catalyzed [3 + 2] cycloadditions to electron-deficient olefins. Once again, it involves the use of palladium(O) complexes in the presence of a phosphane ligand [bis(diphenylphospino)ethane (dppe) or tributylphosphane], A vinylcyclopropane geminally ring-substituted by ester functionalities enables realization of such a process52. 

Unlike reactions with alkenes and alkynes, relatively few examples of intramolecular transition metal-cataly2ed reactions of allenes have been reported so far. Continuing our endeavor to extend the synthetic reach of transition-metal-catalyzed reactions, we have directed our attention at the use of an allene as the n-system. As with the alkene systems, two stereochemical outcomes are possible for the intramolecular [5+2] cycloaddition of allene-vinylcyclopropanes. The use of an allene moiety also presents an interesting opportunity to incorporate chirality into the substrate. Additionally, because ene-vinylcy-clopropane substrates substituted at the alkene terminus are not amenable to [5+2] cycloaddition, the use of an allene allows access to the same framework that would be obtained by cycloaddition of terminally substituted alkene substrates, thereby circumventing one of the few limitations encountered with ene-vinylcyclopropane cycloadditions. 

The first example of the transition-metal-catalyzed [5+2] cycloaddition of vinylcyclopropane (VCP) with alkyne was reported in 1995 by Wender et al. (Scheme 2-73). Various tethered alkyne-VCPs underwent Rh-catalyzed [5+2] cycloaddition to give bicyclo[5.3.0] products 512 in excellent yields, irrespective of the steric and electronic properties of the R group. 

Wender, P. A., Takahashi, H., Witulski, B. (1995). Transition metal catalyzed [5-1-2] cycloadditions of vinylcyclopropanes and atkynes a homolog of the Diels-Alder reaction for the synthesis of seven-membered rings. Journal of the American Chemical Society, 117,4720-4721. 

Other metal-catalyzed [5+2] cycloadditions of vinylcyclopropanes and 7t-systems... 

Other Metal-Catalyzed [5+2] Cycloadditions of Vinylcyclopropanes and tt-Systems... 

Vaska s complex catalyzed the transformahon of aUenylcyclopropane into 2-alkenylidenecyclohex-3-enone under conditions of pressurized CO (Scheme 11.25) [38]. In this reaction, the jr-coordination to internal oleflnic moiety of the aUene brings the metal closer to the cyclopropane ring. Release of the cyclopropane ring strain then facilitates the oxidative addition of vinylcyclopropane moiety along with C-C bond cleavage, such that metallacyclohexene is obtained a subsequent carbonyl insertion and reductive elimination then provides the product Hence, the reaction can be recognized as a [5+1] cycloaddition of vinylcyclopropane and CO. 

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