Cycloadditions of vinylcyclopropanes with

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,... 

Cycloalkenes. [5+2]Cycloaddition of vinylcyclopropanes with alkenes using (Ph3P)3RhCl and AgOTf results in cycloheptenes. Allenylcyclopropanes are subject to... 

In 1987, Tsuji reported for the first time the racemic palladium-catalysed 1,3-dipolar cycloaddition of vinylcyclopropanes with aryl isocyanates to give the corresponding 5-lactams. ° In 2008, Johnson et al. developed racemic palladium-catalysed cycloadditions of vinylcyclopropanes with aldehydes for the formation of tetrahydrofurans. Inspired by these pioneering results, Kura-hashi and Matsubara have recently developed nickel-catalysed 1,3-dipolar cycloaddition of vinylcyclopropanes with imines to give regioselectively the corresponding substituted pyrrolidine derivatives. As shown in Scheme 1.15,... 

In 2012, the first general example of Rh(I)-catalyzed [5-1-1] cycloaddition of vinylcyclopropanes with CO was reported by Yu s group [11]. The reaction was conducted under two different conditions (conditions A and B, Scheme 3) to provide selectively nonconjugated or conjugated products, respectively. The presence of 4-A molecular sieves was found to be essential to the reactions. The reaction can accommodate VCP substrates with different functional groups and substitution patterns, as illustrated in Scheme 3. 

Cycloaddition reactions of cyclopropanes via cleavage of the C—C bond have been apphed to the synthesis of a wide variety of natural products, particularly terpenoids. For example, (-H)-dictamnol [5], (-H)-aphanamol I [6], (-H)-tremulenolide A [7], and (-l-)-lirondosin A [8] were synthesized through a [5-h2] cycloaddition reaction of vinylcyclopropanes with C—C unsaturated bonds. ( )-Hirsutene [9], ( )-pentalenene [10], ( )-asterisca-3(15),6-diene [10], ( )-hirsutic acid [11], and (-l-)-asteriscanohde [12] were synthesized via rhodium(l)-catalyzed [5-H2-H1] cycloaddition of vinylcyclopropanes with alkenes and carbon monoxide. Total syntheses of ( )-a-agarofuran [13], and ( )-pyrovellerolactone [14] were also achieved through cycloaddition reactions of cyclopropane derivatives. For these syntheses, reference to the papers should be made directly. 

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. 

In a study of vinylcyclopropanes with tetranitromethane (TNM), from 1,1-divinylcyclopropane 156, a specific 1,4-diene, the unexpected product 118, was obtained. The formation of the nitronic ester was accompanied by homo-allylic rearrangement, followed by the intramolecular 1,3-dipolar cycloaddition (Equation 9) <2002DOC9>. 

Cyclobutane formation, occasionally in fairly low yield due to ring-opening reactions, also occurred by photochemical [2 - - 2] cycloaddition of vinylcyclopropane derivatives to an a, -unsaturated ketone moiety, " a cyclobuta-1,3-diene, a 1,4-benzoquinone, 2-acylthiophenes, and on irradiation of e t/o,enr/o-2,4-bis[( )-2-(methoxycarbonyl)vinyl]bi-cyclo[1.1.0]butane. A formal [2-1-2] cycloaddition also occurred on reaction of tricyclo[3.1.0.0 ]hex-3-ene with methyl 6-oxo-5-phenyl-l,3,4-oxadiazine-2-carboxylate to give methyl 9-oxo-10-phenyl-8-oxapentacyclo[4.4.0.0 ". 0 .0 °]decane-7-carboxylate, albeit in very low yield, after nitrogen extrusion. ... 

Table 5. [2n + 2n] and [2n + 2cr] Products from the Cycloaddition Reactions of Vinylcyclopropanes with Dienophiles... 

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. 

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. 

Wender s group has also developed rhodium-catalyzed intermolecular [5-1-2] cycloadditions. At first, they found the catalysis system of Rh(PPh3)3Cl for the intramolecular reactions was not effective at all for the intermolecular reactions. To effect the intermolecular [5-1-2] cycloadditions, [Rh(CO)2Cl]2 must be used and oxygen substitution of the cyclopropane was necessary (see (17)) [37-39]. Then they successfully expanded the substrate to unactivated vinylcyclopropanes by adjusting the substituents. For monosubstituted alkynes, the substitution on the olefin terminus directs the formation of single isomer that minimized steric hindrance (see (18)) [40]. The [5-1-2] cycloadditions can also be applied to VCPs with allenes (see (19)) [41]. It should be noted that the alkyne substituent did not interfere with the reaction, indicating that allenes as reaction partners were superior to alkyne in the [5-1-2] cycloadditions. Curiously, the authors didn t report the corresponding intermolecular [5-1-2] cycloadditions of VCPs with alkenes. 

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. 

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. 

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]. 

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]. 

As a related reaction, the bicyclo[5.3.0]decane derivative 64 was obtained at 30 °C by the Rh-catalysed intramolecular [5+2] cycloaddition of the alkyne with the vinylcyclopropane moiety in 61. The latter behaves as a pseudo-1,3-diene in oxidative addition, and generates 62. This is followed by rearrangement to 63, whose reductive elimination gives 64 [20]. [Rh(CO)2Cl]2 is a better catalyst than RhCUPl+P. The reaction can be extended to alkenes [20a],... 

Eq. 52 and 53 demonstrate remarkable characteristics of this [3 + 2]-cycloaddition starting with a pure diastereomer 130, two stereoisomeric cyclopentanes 131 are obtained. This stereorandom outcome is most simply rationalized assuming a stepwise mechanism with a 1,5-zwitterion as an intermediate in the cycloaddition. The vinylcyclopropane 132 only gives five-membered ring products 133 and no cyclo-heptene derivative, which would result from a conceivable [5 + 2]-cycloaddition. Less activated olefins or cyclopropanes do not undergo a similar [3 + 2]-cycloaddition. Due to the specific substitution pattern, the cyclopentane formation from these siloxycyclopropanes is of no preparative value. 

Whereas Fischer-type chromium carbenes react with alkenes, dienes, and alkynes to afford cyclopropanes, vinylcyclopropanes, and aromatic compounds, the iron Fischer-type carbene (47, e.g. R = Ph) reacts with alkenes and dienes to afford primarily coupled products (58) and (59) (Scheme 21). The mechanism proposed involves a [2 -F 2] cycloaddition of the alkene the carbene to form a metallacyclobutane see Metallacycle) (60). This intermediate undergoes jS-hydride elimination followed by reductive elimination to generate the coupled products. Carbenes (47) also react with alkynes under CO pressure (ca. 3.7 atm) to afford 6-ethoxy-o -pyrone complexes (61). The unstable metallacyclobutene (62) is produced by the reaction of (47) with 2-butyne in the absence of CO. Complex (62) decomposes to the pyrone complex (61). It has been suggested that the intermediate (62) is transformed into the vinylketene complex... 

While simple unactivated cyclopropanes have yet to be used for [3 + 2] cycloaddition, Tsuji and coworkers have developed a palladium-catalyzed cycloaddition reaction using electron-deficient vinylcy-clopropanes. Thus, vinylcyclopropane (43) undergoes smooth cyclization with methyl acrylate in the presence of a palladium catalyst to give vinylcyclopentane (44) as a mixture of diasteroisomers (equation 35). The cycloaddition probably proceeds through the zwitterionic ( ir-allyl)palladium intermediate (45) and its stepwise reaction with the acrylate (equation 36). Enones such as cyclopentenone and methyl vinyl ketone will also react. Reaction of the same vinylcyclopropane with phenyl isocyanate produces vi-nyllactam (46) (equation 37).Some cycloaddition reactions with (cyclopropyl)Fp complexes have also been reported. However, the substrates are limited to SO2 and TCNE and the yields have not been disclosed (equation 38). ... 

Vinylcyclopentane derivatives (99) are prepared from the palladium(0)-catalyzed cycloaddition reaction of vinylcyclopropane (98), bearing two election-withdrawing groups, with electron deficient al-kenes (equation 42 and Table 7). The reaction can be formally envisaged as a 1,3-dipolar cycloaddition. 

With the exception of vinylcyclopropane-cyclopentene rearrangements (cf. Section VII) radical reactions have so far rather rarely been used synthetically. This is also true for pericyclic modes of cyclopropane cleavage which are mainly restricted to divinylcyclopropane-cycloheptadiene type expansions. Cycloadditions, whether concerted or stepwise, occur only with very specific compounds. ... 

Cycloadditions of electrophilic olefins or cumulenes to vinylcyclopropanes should also be mentioned in this context, since in most cases stepwise reactions starting with an electrophilic attack are very likely. One example operating with chlorosulphonyl isocyanate and providing a seven-membered lactam is depicted in equation 152 however, so far most reactions in this area have a limited synthetic potential. 

The reactivity of these promising building blocks has very recently been reviewed by de Meijere S therefore only a few principles will be discussed in this text. Treatment with n-butyllithium as outlined in equation 187 will give certain functionalized alkynylcyclopro-panes , which can serve as active components in cycloadditions or reactions with olefins in the presence of Co2(CO)g. The latter [2 + 2 + l]-addition provides cyclopropyl cyclopentenones capable of undergoing vinylcyclopropane-cyclopentene rearrangement. 

Cycloaddition reactions with vinylcyclopropanes.5 a-Cyclopropylstyrene (1) does not react with maleic anhydride. However, it reacts with the more reactive dienophile PTAD to give the 2 1 adduct (4). This adduct is probably formed by cycloaddition of... 

Vinylcyclopropane complexes can be obtained by [2-F1] cycloaddition of transition-metal car-bene complexes to dienes. Thus, formation of a complexed bicyclo[3.1.0]hex-2-ene system 7 was achieved by [2-Fl] cycloaddition of pentacarbonyl(4-methoxybenzylidene)molybdenum to cyclopenta-1,3-diene. The complexed cyclopropanation product 7 upon treatment with oxygen gave end(7-6-(4-methoxyphenyl)bicyclo[3.1.0]hex-2-ene (8) in low yield. 

According to Nishida ° the [27t-l-27r] cycloadditions proceed via dipolar intermediates, whereas the [2n + 2(7] cycloadditions start with a single-electron-transfer process. In [27i-l-27t] additions a deeply colored charge-transfer complex is initially formed and the reaction is favored by polar solvents (as is usually the case with [2jt-l-2jt] additions of TCNE to electron-rich alkenes). Vinylcyclopropanes with a very low ionization potential afford the [2 t-f 2(t] product they do not form a charge-transfer complex with TCNE and the reactions have to be performed under oxygen-free conditions (Table 5). 

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