Cyclopropenes cycloaddition

Structurally novel cyclopropane-fused cycloalkanes can be constructed by oligomerization of cyclopropenes. Cycloaddition across the double bond reduces ring strain in cyclopropenes enormously. When catalysed by transition metals, dimethyl-cyclopropene tri- or tetramerizes stereoselectively to novel polycycloalkanes (equation... 

Cyclopropenes cycloaddition-ring opening with - 32, 630 diene synthesis with -30, 469s31... 

Various carbene-transfer reactions can be used with both electron-rich and electron-poor alkynes to make fluorinated cyclopropenes [9. 13, 79, 80, 81, 82] (Table 4). Haloacetylenes are too thermally unstable for most cycloaddition conditions, and simple fluorinated cyclopropenes are made by other methods [32, 45, 83, 84] (equations 30-32). 

Similarly, partially fluorinated and perfluorinated methylenecyclopropanes [57, 52], cyclopropenes [55, 84, 55], cyclobutenes [75, 56], and bicychc alkenes [57, 55, 59, 90] apparently denve dienophilic reactivity from relief of their ground-state strain during reaction Thus 2,2-difluoromethylenecyclopropane and perfluoromethylenecyclopropane undergo exclusive [244] cycloadditions [57, 52] (equations 72 and 73), whereas (difluoromethylene)cyclopropane undergoes only [24-2] cycloadditions [57]... 

The similarity between the reactions of alkenes and cyclopropanes is further demonstrated by the reactions of electrophilic cyclopropanes and cyclopropenes with enamines. Cyclopropylcyanoester74, when treated with the pyrrolidine enamine of cyclohexanone, undergoes what would be a 1,2 cycloaddition in the analogous alkene case, but is actually a 1,3 cycloaddition here, to form adduct 75 (90). A similar reaction between the... 

Strained bicyclic compounds can be obtained e.g. when cyclopropenes are used as dipolarophiles. Reaction of 3,3-dimethylcyclopropene 7 with diazomethane 4 gives the heterobicyclic cycloaddition product 8 in 85% yield ... 

The inverse electron demand Diels-Alder [4 + 2] cycloadditions of methyl 1,2,4-triazine-3-carb-oxylates 36 (cf. Section B.2.2.) with cyclopropene followed by loss of nitrogen from the unstable cycloadducts 37 provide useful access to 4//-azepine-2-carboxylates 38.83-85... 

Treatment of methyl 6-phenyl-l,2,4-triazine-3-carboxylate (41) with cyclopropene produces methyl 6-phenyl-4//-azepine-2-carboxylate (42) in equilibrium with its bicyclic valence tautomer 43, which undergoes a second cycloaddition with cyclopropene to yield the bisadduct 44.112... 

A recent variation of these reactions uses 6/f-l, 3-oxazin-6-ones as the electron-deficient heterodiene in place of the triazine.113114 With cyclopropene at — 35 C oxazinone 45 furnishes the 4//-azepine 46 in excellent yield. Likewise, with 3-methylcyclopropene the 4-methyl derivative 46 (R = Me) is formed. Cycloaddition with 1-methylcyclopropene, however, generates a mixture of 7-tert-butyl, 2-methyl 3-methyl- and 5-methyl-4//-azepine-2,7-dicarboxylate in a 2 1 ratio and a 97 % overall yield. 

As with the 1,2,4-triazines,83 temperature control during these cycloadditions is important, since additions at 0-25 C result in the formation of 2 1 cyclopropene-azepine cycloaddition products.113... 

Similarly, 4//-azepinc-2-carboxylates 16, obtained by cycloaddition of 1,2,4-triazines with cyclopropenes (see Section 3.1.1.1.2.), isomerize in practicable yields to 3//-azepines 17 in refluxing pyridine,84-85 or with sodium methoxide in refluxing methanol.28-83... 

An interesting cycloheptatriene (182) synthesis has been described using thiophene 1, 1-dioxides (180) and cyclopropenes 181 (equation 121)ns. Concerted [4 + 2]cycloaddition and subsequent cheletropic extrusion of sulfur dioxide are suggested by the second-order kinetics (first in each reactant), and by the large negative activation entropy. 

Padwa A., Fryxell G. E. Cyclization and Cycloaddition Reactions of Cyclopropenes Strain Org. Chem. 1991 1 117-166... 

Whereas the Rh2(OAc)4-catalyzed addition of diazoalkanes to propargyl alcohols readily gives the insertion of the carbene into the 0-H bond, with only a small amoimt of cyclopropenation of the resulting propargylic ether [54] the 2-diazopropane 59 reacts at 0 °C with l,l-diphenyl-2-propyn-l-ol 62a in dichloromethane and exclusively gives, after 10 h of reaction, only the adduct 63a isolated in 75% yield and corresponding to the regioselective 1,3-dipolar cycloaddition of the 2-diazopropane to the alkyne C - C bond (Scheme 15). 

Trimethylenemethane is a special type of alkene that does not exist as the free compound. Various synthetic equivalents to the synthon 43 shown below have been reported. Trost, in particular, has exploited these compounds in 1,3-dipolar cycloaddition reactions.138 139 A metal-bound, isolated trimethylenemethane species was recently reported by Ando (Scheme 6). It resulted from the complexation of an ero-methylenesila-cyclopropene with group 8 carbonyls (Fe, Ru).140,140a The structure was proved by X-ray crystal structure analysis.29Si NMR data were consistent with the -structure shown. 

Alkinyloxy)diazoacetic esters 11 give rise to product mixtures that could be separated only partially. The isolated products result from a tandem intramolecular cyclopropenation/cyclopropene —> vinylcarbene isomerization (12, 14) and from a twofold intermolecular (3+2)-cycloaddition of the intact diazo compound (13). 

Ethyl diazopyruvate, under copper catalysis, reacts with alkynes to give furane-2-carboxylates rather than cyclopropenes u3) (Scheme 30). What looks like a [3 + 2] cycloaddition product of a ketocarbenoid, may actually have arisen from a primarily formed cyclopropene by subsequent copper-catalyzed ring enlargement. Such a sequence has been established for the reaction of diazoacetic esters with acetylenes in the presence of certain copper catalysts, but metallic copper, in these cases, was not able to bring about the ring enlargement14). Conversely, no cyclopropene derivative was detected in the diazopyruvate reaction. 

Although diarylmethylenecyclopropabenzenes react in [4 + 2] cycloadditions at the cyclopropene bridge bond [10a], diarylmethylenecyclopropa[b]-naphthalenes 14 react readily across the exocyclic double bond [10b]. The... 

Diarylmethylenecyclopropa[6]naphthalenes 14, unlike their benzene parent counterparts which give cycloaddition reactions at the cyclopropene bridge bond [10a], react on the exo double bond in Diels-Alder cycloadditions (see Sect. 2.1.1) [10b]. The reactions of 14 with the highly electron-deficient acetylenic(phenyl)iodonium triflate 584 give products 586a and 587, which are believed to derive from unstable primary [2 + 2] cycloadducts 585 (Scheme 82) [10b],... 

Cycloaddition of the carbene chromium complexes 97 with CO incorporation provides a versatile method for naphthol synthesis, in which the metallacy-clic intermediates 99 are involved [47]. An alternative entry to 101 is achieved by metal carbonyl-catalyzed rearrangement of the cyclopropenes 98 via the same metalla-cyclobutenes 99 and vinylketene complexes 100 [52], Mo(CO)6 shows a higher activity than Cr(CO)6 and W(CO)6. The vinylketene complex 103 is formed by the regioselective ring cleavage of 1,3,3-trimethylcyelopropene 102 with an excess of Fe2(CO)9 [53]. (Scheme 35 and 36)... 

Cycloaddition of cyclopropenes is catalyzed by transition metal complexes. 1-Methylcyclopropene 118 undergoes a facile PdCl2(PhCN)2-catalyzed cyclodimerization to dimethyltricyclo[3.1.0.02,4]hexanes 119. In contrast, cyclo-trimerization of 3,3-dimethylcyclopropene 120 occurs in the presence of a catalytic amount of Pd(PPh3)4 to give hexamethyl-frans-ff-trishomobenzene 121... 

The ring expansion reaction of diaryl cyclopropenones and cyclopropene thiones occurring with pyridinium, sulfonium, and phosphonium enolate betaine 427268-270) is related to 1,3-dipolar cycloadditions. This process results in formation of 2-pyrones 428 by loss of pyridine (or sulfide or phosphine) and insertion of the remaining fragment C=C-0 to the C1(2)/C3 bond of the cyclopropenone ... 

Acetylene dicarboxylate and maleic anhydride failed to react with simple methylene cyclopropenes, but reacted readily with calicene derivatives, as shown by Prinz-bach293. Thus ADD combined with benzocalicene 497 to give the dimethyl tri-phenylene dicarboxylate 499, whose formation can be rationalized via (2 + 2) cycloaddition across the semicyclic double bond as well as (4 + 2) cycloaddition involving the three-membered ring (498/501). The asymmetric substitution of 499 excludes cycloaddition of ADD to the C /C2 triafulvene bond (500), which would demand a symmetrical substituent distribution in the final triphenylene derivative. 

Cycloalkene Derivatives Cyclopropenes readily interact with nitrile oxides. Reactions of a broad series of 3,3-disubstituted cyclopropenes with 4-substituted benzonitrile, methoxycarbonyl- and cyanoformonitrile oxides (229) as well as with di(isopropoxy)phosphorylformonitrile oxide (230) give 2-oxa-3-azabicyclo[3.1.0]hexene derivatives 62. Stereoselectivity of the cycloaddition is governed by both steric and polar factors. In particular, steric factors are supposed to prevail for 3-methyl-3-phenylcyclopropene affording 62 [R1 =... 

As mentioned in Sections 3.1.6 and 4.1.3, cyclopropenes can also be suitable starting materials for the generation of carbene complexes. Cyclopropenone di-methylacetal [678] and 3-alkyl- or 3-aryl-disubstituted cyclopropenes [679] have been shown to react, upon catalysis by Ni(COD)2, with acceptor-substituted olefins to yield the products of formal, non-concerted vinylcarbene [2-1-1] cycloaddition (Table 3.6). It has been proposed that nucleophilic nickel carbene complexes are formed as intermediates. Similarly, bicyclo[1.1.0]butane also reacts with Ni(COD)2 to yield a nucleophilic homoallylcarbene nickel complex [680]. This intermediate is capable of cyclopropanating electron-poor alkenes (Table 3.6). 

In contrast, isomers of 115 have so far not been isolated. An early attempt to generate cyclopropa[a,e]naphthalene (118) failed. More recently, the generation of dicyclopropa[a,c]naphthalene (119) was attempted by reaction of 120 with base. When the aromatization was carried out in the presence of DPIBF (44), stereoi-someric bis-adducts of cyclopropenes were isolated. However, the adducts provide no evidence for the formation of 119 as a reactive intermediate, since they are formed by sequential elimination-cycloaddition via 121. Cyclopropene interception of 121 is faster than further elimination to 119. The failure of the reaction to produce 119 has been attributed to the high strain energy of the product, which is estimated some 2 8 kcal/mol higher than that expected for two isolated cyclopropene units. ... 

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