Cyclopropylidene

Data for substituted cyclopropane rings can be conveniently arranged in five categories substituted cyclopropane sets, cyclopropylidene sets, trans-cyc o-propylene sets, cis-cyclopropylene sets, and reactions of cyclopropane rings. The correlation of data for cyclopropanes with the Hammett equation (19) and the extended Hammett equation (215) has been reported by Charton. 

The vinylidene group, the rro s-CPh=C- group, and the methylene group, all of which have one atom intervening between the substituent and the reaction site, all show Ji values of about 4. The cyclopropylidene group is an exception to this observation, with Ji of 6.38. As there were only four points in the set from which a was obtained, this deviation may not be real. The C—CPh=C group has a somewhat low value for 7j of 3.39. 

Zhou S, Breitenbach JM, Borysko KZ, Drach JC, Kern ER, GuUen E, Cheng YC, Zemhcka J (2004) Synthesis and antiviral activity of (Z)- and (E)-2,2-[bis(hydroxymethyl) cyclopropylidene]methylpurines and -pyrimidines second-generation methylenecyclopropane analogues of nucleosides. J Med Chem 47 566-575... 

Acetylene- and Diacetylene-Expanded Cycloalkanes and Rotanes. 201 1 -42 de Meijere A, Kozhushkov SI, Khlebnikov AF (2000) Bicyclopropylidene - A Unique Tetra-substituted Alkene and a Versatile Cj-Building Block. 207 89-147 de Meijere A, Kozhushkov SI, Hadjiaraoglou LP (2000) Alkyl 2-Chloro-2-cyclopropylidene-acetates - Remarkably Versatile Building Blocks for Organic Synthesis. 207 149-227 Dennig J (2003) Gene Transfer in Eukaryotic Cells Using Activated Dendrimers. 228 227-236 de Raadt A, Fechter MH (2001) Miscellaneous. 215 327-345 Desreux JF, see Jacques V (2002) 221 123-164... 

Semi-empirical molecular orbital calculations have been carried out on the model phosphorane HaPiCHa. Besides the expected transfer of charge, the inclusion of the phosphorus 2>d orbitals showed a significant hyperconjugative interaction between the CHg orbitals and a 2>d orbital of appropriate symmetry on phosphorus. Calculations on cyclopropylidene-phosphorane revealed a similar interaction between the Walsh orbitals of the ring and an in-plane phosphorus 2>d orbital. 

Sulfur ylides can also transfer substituted methylene units, such as isopropylidene (Entries 10 and 11) or cyclopropylidene (Entries 12 and 13). The oxaspiropentanes formed by reaction of aldehydes and ketones with diphenylsulfonium cyclopropylide are useful intermediates in a number of transformations such as acid-catalyzed rearrangement to cyclobutanones.285... 

Cyclopropylidenes undergo ring opening to give allenes. Reactions that would be expected to generate a cyclopropylidene therefore lead to allene, often in preparatively useful yields. 

In their synthesis of spirocyclopropanated oxazolines (see Section 2.1), the de Meijere group obtained initially unexpected cyclobutene-annelated pyrimidones 2-569 by reaction of the cyclopropylidene derivative 2-567 with the amidines 2-568. In this fourfold anionic transformation a Michael addition takes place to furnish 2-570, which is followed by an isomerization affording cyclobutenecarboxylates 2-572 and a final lactamization (Scheme 2.128) [294]. 

This procedure was used for the asymmetric total synthesis of the steroid (+)-equilenin (7-7) [3]. Cyclopropylidene derivates 7-4 could be converted into the cyclobutanones 7-5 in good yields by applying an asymmetric epoxidation using the chiral (salen)Mnm complex 7-6 (Scheme 7.2) [4]. It is of interest that the demethoxy-lated substrate 7-4b led to 7-5b with a very high enantiomeric excess of 93%, whereas 7-4a gave 7-5a with only 78% ee. 

Several of the compounds identified in ISM have not so far been synthesized in the laboratory however, two of them have now been obtained. The cyclic compound cyclopropylidene (C3H2), first detected in ISM in 1985 and later more frequently, was considered to be too unstable to exist on Earth under laboratory conditions. A derivative of this carbocycle, stabilized by amino groups which serve as -donors, has now been reported. X-ray crystallography shows that the presence of the amino groups has little effect on the molecular geometry as calculated for the unsubstituted cyclopropylidene (Lavallo et al., 2006). 

The relative reactivities of several of these 2-hetero substituted 2-cyclopropylideneacetates 4 and 53-55 as well as of the parent 2-cyclopropylidene-acetate 52 and acrylates 56a-d towards 6,6-dimethylfulvene (57) and furan (7) were determined by competition experiments [17,19] (Table 5). The endo/exo selectivity is low, but usually still higher than for simple acrylic esters. 

These experimental findings, as well as earlier data on alkylidenecyclopropanes, clearly disclose a peculiar effect of a cyclopropylidene system both on reaction rates and regioselectivity. In fact, the parent MCP as well as its derivatives exhibit a high reactivity in 1,3-dipolar cycloadditions with nitrones. In contrast, the related open chain isobutene and its derivatives are well known to enter 1,3-dipolar cycloadditions sluggishly [51c-d, 70]. For example, there is no chance to obtain a cycloadduct from 256 and an open chain trialkyl or tetraalkylethylene, as was obtained in the reaction of 256 with 270 and 271. 

The unstable 2-cyclopropylidene-l,3-cycloalkanediones 34a,c,d were trapped in situ by isocyanides 391 to give [4 + 1] cycloadducts under mild reactions conditions to afford 3-spirocyclopropane furans or pyrroles (Table 32) [95]. In the case of 34a, the primary cycloaddition products 392 and 394 decomposed very easily to give the stable pyrrolidindiones 393 and 395, respectively, as a single stereoisomer, upon addition of methanol (entries 1-2). Compounds 34c and 34d gave the expected adducts in moderate to good yields (Table 32, entries 3-7). 

Salaun and de Meijere s groups have applied successfully the intramolecular PKR on 1-cyclopropylidene-1,6-enynes 421-426 (Table 34) [108], accessible via the Pd(0) catalysed alkylation of stabilized carbanions with 1-vinylcyclo-propanes 1-substituted with leaving groups [3a, 109]. 

PTAD reacts very rapidly with alkenylidenecyclopropanes 600 attacking only the cyclopropylidene substituted double bond, but exclusively with ringopening giving [3 + 2] cycloadducts 601 (Scheme 84) [44,159]. Finally, it gives the [2 + 2] adduct 603 by reaction with 2,3-trans-dimethylmethylenecyclop-ropane (602), albeit reacting much more slowly (Scheme 84) [44,159b]. 

Transition metals 172 a-bonded to cyclopropanes, substituted on the a-carbon with a halogen atom, are interesting intermediates for cyclopropylidene complexes 173 or allene ones 174 [88]. The former complexes are also supposed to be precursors of the above-mentioned nickel enolates. (Scheme 65)... 

Tandem cyclization of l-cyclopropylidene-5-methylenecyclooctane (233) with palladium ) chloride/triphenylphosphine in the presence of diisobutylaluminium hydride leads to the [3.3.3]propellane 235 in 74% yield by way of the proposed intermediate 234 (L = ligand) (equation 119)120. 

The GIAO-MP2/TZP calculated 13C NMR chemical shifts of the cyclopropylidene substituted dienyl cation 27 show for almost all carbon positions larger deviations from the experimental shifts than the other cations 22-26. The GIAO-MP2/TZP method overestimates the influence of cr-delocalization of the positive charge into the cyclopropane subunit on the chemical shifts. Electron correlation corrections for cyclopropylidenemethyl cations such as 27 and 28 are too large to be adequately described by the GIAO-MP2 perturbation theory method and higher hierarchies of approximations such as coupled cluster models are required to rectify the problem. 

The formula of the smallest ring including a complete allene moiety is that of cyclo-propadiene (11) (Scheme 6.5). However, this structure does not seem to be an energy minimum at the C3H2 hypersurface [21]. Cyclopropylidene (12) was calculated to be the most stable species followed by open-chain isomers [22]. 

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