Cyclopropylidene derivative

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. 

Cyclopropylidenes derived from acetyl- or formyl-gem-dibromocyclo-propane dimethylacetals 233 and methyllithium insert into the a-C—H bond of an alkyl group to produce bicyclic products 234 [83ACS(B)681 88ACS(B)475]. 

In the presence of phenyllithium the reagent reacts with-carbonyl compounds to give cyclopropylidene derivatives 2... 

De Meijere showed that reactions of cyclopropylidene derivatives lead to amino-cyclopropane carboxylic acids via conjugate addition of an amine surrogate. Reac-... 

The addition of arenesulfonyl derivatives to the double bond of vinylcyclo-propanes leads to 1,5-adducts via a ring opening of cyclopropylcarbinyl radicals. Equation (58) shows an example of copper (I)-catalyzed addition of benzenesul-fonyl chloride to poly substituted vinylcyclopropanes [117]. Similar chemistry has been observed for the addition of selenosulfonates to cyclopropylidene derivatives and cyclopropylacetylene [118]. 

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). 

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. 

Analogous transformations have also been reported for the tetramethylbi-cyclopropylidenes 24b,c [99, 1001, the bicyclopropylidene 22a of Moore and Ward [1011, tetramethyldichlorobicyclopropylidene 28a [46], and 1,1-dideuter-iobicyclopropylidene [51]. The mechanistic and kinetic aspects of these rearrangements as well as subsequent transformations of the resulting methylene-spiropentanes to dimethylenecyclobutane derivatives at higher temperatures have been reviewed [1021. 

The electrophilic reaction of magnesium cyclopropylidene (113) with Ai-lithioaryl-amines was reported (equation 31) . Thus, electrophilic reaction of magnesium cyclopropylidene (113) derived from 112 with iV-lithio iV-methyl p-anisidine resulted in the formation of a-amino-substituted cyclopropylmagnesium (119) in good yield. Methanol-ysis of the reaction mixture with CH3OD gave a-deuteriated Af-cyclopropyl-Af-methyl-p-anisidine (120) in 82% yield with 98% D-content. 

TABLE 5. Reaction of magnesium cyclopropylidene (113) derived from 1-chlorocy-clopropyl phenyl sulfoxide (112) with Al-hthio amines... 

Occasionally the cyclopropylidene to allene isomerization cannot take place for structural reasons. If, for example, the expected allene would be very highly strained, as is the case for certain cyclic allenes, then the reaction is forced to follow an alternative path. A case in point is provided by 1-alkyl-7,7-dibromonorcaranes which undergo a carbene insertion reaction when treated with methyl lithium to provide bicyclobutanes rather than allene derivatives. 

Substituted cyclopropylidenes have been shown to participate in both inter-and intramolecular addition reactions with olefins. The resulting products are spiropentane derivatives as well as carbene dimers which are formed as side-products [99, 100]. In the absence of olefinic reaction products the latter may even become the main products [99 b],... 

It is interesting to note that the yield of 39 can be increased to 95 % in the presence of a Ni(0) catalyst (see Section I.3.I.2.).43 In unsymmetrically substituted buta-l,2,3-trienes, head-to-head dimerization takes place as well, as seen in the examples below.44 The intermediate cyclopropy-lidenecumulenes 41 are formed from vinylidene insertions into alkenes and reactions occur at the terminal unsaturated site of the cyclopropylidene group. Structures 42 were confirmed by X-ray crystallographic analysis and revised the original assignment of the head-to-tail structures for these derivatives.45... 

Poutsma and Ibarbia s (1971) work on 2-methyl-l-(tetramethyl-cyclopropylidene)propene (65) showed that chlorination (in CC14) yields derivative 99 exclusively. Bromination of 65 (methanol, 25°) gives a more complex mixture of products ranging from the bromine analogue of 99 to compounds of type 100. Terminal electrophilic attack or, at least if bridged species are involved, SNl-type ring opening is apparently involved in these cases. 

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