Methylenecyclopropane derivatives

Due to their tendency to dimerize in different thermal conditions, the formal [2 + 2] cycloaddition reaction of methylenecyclopropane derivatives and their... 

Albeit the transition metal catalysed reactions of methylenecyclopropane derivatives have already been thoroughly reviewed [2], it should be noted here that the cyclodimerization of these compounds can also be achieved by catalysis with Ni or Co complexes. The regioselectivity of the process is surprising and opposed to that of the thermal reaction, giving dispiro[2.1.2.1]octane derivatives (Scheme 69) [2],... 

Ethenylcyclopropyl tosylates 131 and 2-cyclopropylideneethyl acetates 133, readily available from the cyclopropanone hemiacetals 130, undergo the re-gioselective Pd(0)-catalyzed nucleophilic substitution via the unsymmetrical 1,1-dimethylene-jr-allyl complexes. For example, reduction with sodium formate affords a useful route from 131 to the strained methylenecyclopropane derivatives 132. The regioselective attack of the hydride is caused by the sterically... 

The stabilized anion 134 also attacks the terminal vinylic position of 131 exclusively to give cyclopropylideneethyl derivatives 135, which are synthetically useful building blocks [69], The use of chiral phosphanes as ligands leads to optically active methylenecyclopropane derivatives. (Scheme 47)... 

The kinetics of these reactions in comparison with those for methylenecyclo-propane analogs of compounds 160 have been studied by following the progress at pressures up to 3 kbar by on-line FT-IR spectroscopy [129]. The rate-enhancing influence of the additional strain in 160 overcompensates the expected retarding effect of the increased steric shielding by the second cyclopropane unit in 1 compared to methylenecyclopropane, and the cyclization rates for compounds 160 were faster by a factor of 6.8 to 8.1 in comparison with the corresponding methylenecyclopropane derivatives. 

Treatment of bicyclopropylidene (1) with lithium powder led to ring opening and subsequent treatment of the reaction mixture with dimethyl sulfate afforded the methylenecyclopropane derivative 225 and 4-octyne (226) in variable ratios (Scheme 51) [143]. 

On another front, further progress can and will be achieved towards the preparation of bicyclopropylidene analogs of naturally occurring and biologically active methylenecyclopropane derivatives. Two particularly interesting specimens are the naturally occurring 3-(2-methylenecyclopropyl)alanine (287), so-... 

The methylenecyclopropane derivative 3-SPh with its capto-dative substitution pattern has demonstrated essentially the same reaction mode and underwent dimerization to afford a mixture of E) and (Z)-17 (ratio 1.3 1) upon attempted cycloaddition of 3-SPh onto bicyclopropylidene [7h, 291 (Scheme 5). The assignment of these diastereomers was secured by an X-ray crystal structure analysis of E) and (Z)-16 [11c, 30] as well as E)-17 [29]. 

There is no published example of a cyclopropanation of the double bond in chlorocyclopropylideneacetate 1-Me with retention of the chlorine atom. Thus, attempted cyclopropanations under Simmons-Smith [37] or Corey [38] conditions failed [25]. The treatment of the highly reactive methylenecyclopropane derivative 1-Me with dimethoxycarbene generated by thermal decomposition of 2,2-dimethoxy-A -l,3,4-oxadiazoline 26 (1.5 equiv. of 26,PhH, 100 °C,24 h),gave a complex mixture of products (Scheme 7) [39], yet the normal cycloadduct 28 was not detected. The formation of compounds 29 - 33 was rationalized via the initially formed zwitterion 27, resulting from the Michael addition of the highly nucleophilic dimethoxycarbene to the C,C-double bond of 1-Me. The ring closure of 27 to the normal product 28 is probably reversible, and 27 can rearrange or add a second dimethoxycarbene moiety and a molecule of acetone to form 33. 

In conclusion, the chemistry presented here illustrates the broad synthetic applicability of methyl 1-chloro-l-cyclopropylideneacetate (1-Me) and its derivatives. The remarkably efficient method for the syntheses of such compounds presented here, can undoubtedly be applied to generate a large variety of similar methylenecyclopropane derivatives with different substituents. Such chloro esters demonstrate unique reactivities and thereby have a wide potential as... 

Bis(cyclopropyl)titanocene is prepared from cyclopropyllithium and dichloroti-tanocene in 95% yield. The complex has been utilized as an olefination reagent in reactions with a wide variety of carbonyl compounds, including esters, furnishing the corresponding methylenecyclopropane derivatives (equation 13). ... 

With methylenecyclopropane derivatives, C02 again reacted to give lactones (equation 160).594 With complex (105) and PPh3 as catalyst precursor, (129) was formed. Using [Pd(diphos)2] (104) both (129) and (130) were obtained with the latter as major product. 

Path a involves unimolecular decomposition of an initial ozonide (VI). It is important to note that since other methylenecyclopropane derivatives, such as 2,3-dimethylmethylenecyclopropane, do not undergo ring opening of the cyclopropane ring, both ring strain and the presence of the carbomethoxy groups must be necessary for such an unusual decomposition of an initial ozonide. The following sequence rationalizes... 

Kilburn has extensively studied radical cascades centered on the use of methylenecyclopropane derivatives. An addition-fragmentation process ap-parented to pathway c opened new routes for the synthesis of carbocycles. In a recent work, a Sml2-promoted cascade of propargyl ether 73 has been used to give bicyclic ether 78 with good diastereoselectivity (Scheme 24), thus providing a short route to the monoterpenoid paeonilactone B. The observed stereoselectivity in the 74 75 cyclization step was shown to be critically dependent on the presence of HMPA [84]. 

Treatment with potassium hydroxide/methanol and acidic workup will afford an electrophilic methylenecyclopropane derivatives which can add nucleophiles or take part in cycloadditions. A tandem Michael addition of this compound with the enolate of an enone approaches the carbon skeleton of the terpene eremophilane (equation 188) ... 

In the field of olefin carboxylation, stoichiometric reactions have been described to occur between non-activated alkenes, CO2 and an electron-rich transition-metal complexes, such as Ni(0) [3], Ti(II) [4] or Fe(0) [5]. A Pd-catalyzed CO2 fixation occurs into methylenecyclopropane derivatives affording lactones [6]. The reaction of carbon dioxide with ethylene is difficult and its carboxylation to propionic acid, catalyzed by Rh derivatives [7], needs drastic experimental conditions. 

Aryl(methoxy)carbenes, generated photolytically from 3-aryl-3-methoxy-3//-diazirines, underwent addition to 1,1-dimethylallene to give methylenecyclopropane derivatives 1 (no yields or physical properties of the products were reported). ... 

Direct photolysis of cis- and rraH5-bicyclo[5.2.0]non-8-ene (47) in hydrocarbon solution with monochromatic far-ultraviolet (185-214 nm) light sources afforded (Z,Z)- and (Z, )-cy-clonona-1,3-dienes via formal electrocyclic ring-opening, cycloheptene via formal a2s + a2s) cycloreversion and only a small amount of methylenecyclopropane derivative 44. The formation of this three-membered ring has been proposed to arise from a cyclobutylidene, formed as a result of [1,2]-hydrogen migration in the 71,R(3a) state. ... 

Table 2. Methylenecyclopropane Derivatives via Addition of Diazoalkanes to Allenes...

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