Vinylcyclopropanes cycloaddition

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 reaction was also tested with a substrate containing a four-atom tether (Eq. 68). Consistent with our earlier observations, the yield of the cycloaddition improves with increasing substitution of the allene (Eq. 69). Interestingly, the reaction times for substrates with both three- and four-atom tethers are comparable, in contrast to our earlier findings with ene-vinylcyclopropane cycloadditions in which a one-atom increase in tether length profoundly increases the reaction time. 

The reaction of dihalocarbenes with isoprene yields exclusively the 1,2- (or 3,4-) addition product, eg, dichlorocarbene CI2C and isoprene react to give l,l-dichloro-2-methyl-2-vinylcyclopropane (63). The evidence for the presence of any 1,4 or much 3,4 addition is inconclusive (64). The cycloaddition reaction of l,l-dichloro-2,2-difluoroethylene to isoprene yields 1,2- and 3,4-cycloaddition products in a ratio of 5.4 1 (65). The main product is l,l-dichloro-2,2-difluoro-3-isopropenylcyclobutane, and the side product is l,l-dichloro-2,2-difluoro-3-methyl-3-vinylcyclobutane. When the dichlorocarbene is generated from CHCl plus aqueous base with a tertiary amine as a phase-transfer catalyst, the addition has a high selectivity that increases (for a series of diolefins) with a decrease in activity (66) (see Catalysis, phase-TRANSFEr). For isoprene, both mono-(l,2-) and diadducts (1,2- and 3,4-) could be obtained in various ratios depending on which amine is used. 

Adducts derived from cyclopropyl-TMM reactions are versatile synthetic intermediates. Alkylidenecyclopropanes have been proven useful in further Pd-cata-lyzed transformations [4], On the other hand, vinylcyclopropanes can undergo smooth thermal ring-expansion to cyclopentenes. Thus, a total synthesis of 11-hy-droxyjasionone (27) was achieved with the cyclopropyl-TMM cycloaddition as the crucial step, and the thermal rearrangement of the initial adduct (28) as an entry to the bicyclo[6.3.0]undecyl compound (29), a key intermediate in the synthetic sequence (Scheme 2.9) [19]. 

Ferrate 38 also turned out to catalyze [5 + 2]-cycloadditions. In this context, various vinylcyclopropane derivatives 52 were converted into the corresponding cycloheptadiene derivatives 53. The products were obtained in good to excellent diastereoselectivites favoring the 1,2-trans-disubstituted isomer 53a. 

The photoindueed 1,7-cycloaddition of carbon monoxide across the divinyl-cyclopropane derivative 32 yields the two cyclic dienyl ketones 34, via the ferracyclononadiene intermediate 33 [18]. (Scheme 11) cyclopentene rearrangement. The dienylcyclopropane 35 is capable of forming the complex 36, followed by ring enlargement to 37 [19]. 1,1-Dicyclopropylethylene 29 is also converted to the 1-cyclopropyl-1-cyclopentene 38. The additional functionality of vinylcyclopropanes is necessary to serve as a 7t-donor... 

The vinylcyclopropane 144, bearing two electron-withdrawing groups, undergoes the intermolecular palladium-catalyzed [3 + 2]cycloaddition reaction of the Jt-allylpalladium intermediate 145 with a,/ -unsaturated esters or ketones to provide a useful method for forming the cyclopentane ring of 146 [74], (Scheme 51)... 

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. 

Radical [3 + 2 cycloaddition. Cyclopentanes can be prepared by addition of alkenes across vinylcyclopropanes catalyzed by phenylthio radicals formed from (C6H5S)2 and AIBN. A Lewis acid such as A1(CH3)3 can increase the rate and the stereoselectivity of this radical initiated cycloaddition. Thus the combination of the vinylcyclopropyl ester 1 with f-butyl acrylate (2) provides the four possible cyclo-... 

Rhodium-catalyzed [5 + 2]-cycloaddition of an allene and a vinylcyclopropane proceeds with complete chemo-, endo/exo- and diastereoselectivity, representing an effective general route to bicyclo[5.3.0]decane derivatives (Scheme 16.75) [81]. This cydoaddition protocol has been applied successfully to asymmetric total syntheses of natural products [82, 83]. 

Scheme 16.75 Rh-catalyzed intramolecular [5 + 2]-cycloadditions of allenes and vinylcyclopropanes.

In practice, it was found that whereas the synthesis of hirsutene according to the dual strategy met with success under thermal conditions, but at temperatures as high as 580 °C, under photochemical conditions it afforded the unnatural cis, syn, cis configuration of some intermediates which then need further elaboration. Although the transformations 44 — 43a and 45. — 43a by a [2 + 2] -cycloaddition and a vinylcyclopropane rearrangement, respectively, may involve intermediates with a more or less biradical character, they are not typical radical reactions such as the ones we are considering here. 

The rhodium(I)-catalysed 5 + 2-cycloadditions between vinylcyclopropanes and alk-enes (113) yield only di-5,7-fiised cycloadducts (114) in high yields (Scheme 44).i68.i69... 

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. 

The cycloaddition of the carbene 5 to 6 occurs stereospecifically, i.e. with retention of the alkene configuration, and diastereoselectively, i.e. the more bulky trichloroethenyl group ends up predominantly trans to the most bulky substi-tuent(s) on the original alkene 6 [7-10,13]. The high efficiency with which this vinylcarbene can be intercepted intermolecularly to give vinylcyclopropanes is most surprising [14]. 

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. 

Asymmetric induction is possible in the two-step [3-1-2] cycloaddition by starting the sequence with an asymmetric cyclopropanation (Scheme 14.15) [106]. The Rh2(S-DOSP)4-catalyzed reactions gave the desired vinylcyclopropanes 126 with high enan-tioselectivities [106]. Partial or complete racemization occurred in the vinylcyclopro-pane rearrangement of monocyclic vinylcyclopropanes, but the fused vinylcyclopropanes 128-133 rearrange to form 134-139 with virtually no racemization. 

Another unusual two-step [3 + 2] cycloaddition involves the ring expansion of tert-bu-tyl-l-vinylcyclopropane-l-carboxylate 148 to the a-ethylidenebutyrolactone 149 (Scheme 14.18) [108]. When the reaction is catalyzed by boron tribromide the monocycHc product 149 is formed, but when the Lewis acidic oxidant VOCl2(OEt) is used, a very unusual dimeric product (150) is formed. 

Vinylcyclopropanes having two electron-withdrawing groups geminally substituted on the three-mem-bered ring also have been found to serve as 1,3-dipolar equivalents capable of [3 + 2] cycloadditions. 

Although it has been established that the HOMO (diazoalkane)-LUMO (alkene) controlled concerted cycloaddition occurs without intervention of any intermediate for the reactions of simple diazoalkanes with alkenes, Huisgen once proposed a mechanistic alternative 4 namely an initial hypothetical nitrene-type 1,1-cycloaddition reaction of phenyldiazomethane to styrene followed by a vinylcyclopropane-cy-clopentene-type 1,3-sigmatropic rearrangement Control experiments, however, excluded this hypothesis for the bimolecular 1,3-dipolar cycloaddition reaction of diazomethane (Scheme 60).204... 

The [Rh(NHC)Cl(COD)]/AgSbF6-catalysed intramolecular 4 + 2-cycloaddition of dienynes and the intramolecular 5 + 2-cycloaddition of alkyne vinylcyclopropanes formed the corresponding bicyclic cycloadducts in 91-99% yields within 10 min.8... 

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... 

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