Cyclopropane and Cyclopropene Derivatives

The majority of preparative methods which have been used for obtaining cyclopropane derivatives involve carbene addition to an olefmic bond, if acetylenes are used in the reaction, cyclopropenes are obtained. Heteroatom-substituted or vinyl cydopropanes come from alkenyl bromides or enol acetates (A. de Meijere, 1979 E. J. Corey, 1975 B E. Wenkert, 1970 A). The carbenes needed for cyclopropane syntheses can be obtained in situ by a-elimination of hydrogen halides with strong bases (R. Kdstcr, 1971 E.J. Corey, 1975 B), by copper catalyzed decomposition of diazo compounds (E. Wenkert, 1970 A S.D. Burke, 1979 N.J. Turro, 1966), or by reductive elimination of iodine from gem-diiodides (J. Nishimura, 1969 D. Wen-disch, 1971 J.M. Denis, 1972 H.E. Simmons, 1973 C. Girard, 1974), 

Another widely used route to cyclopropanes involves the addition of sulfoniutn ylides to a,/3-unsaturated carbonyl compounds (S.R. Landor, 1967 R. Sowada, 1971 C.R. Johnson, I973B, 1979 B.M. Trost, 1975 A). Non-activated double bonds are not attacked. Sterical hindrance is of little importance in these reactions because the C—S bond is extraordinarily long 

The growing importance of cyclopropane derivatives (A. de Meijere, 1979), as synthetic intermediates originates in the unique, olefin-like properties of this carbocycle. Cyclopropane derivatives with one or two activating groups are easily opened (see. p. 69f.). Some of these reactions are highly regio- and stereoselective (E. Wenkert, 1970 A, B E. J. Corey, 1956 A, B, 1975 see p. 70). Many appropriately substituted cyclopropane derivatives yield 1,4-difunctional compounds under mild nucleophilic or reductive reaction conditions. Such compounds are especially useful in syntheses of cyclopentenone derivatives and of heterocycles (see also sections 1.13.3 and 4.6.4). 

If a bromomethyl- or vinyl-substituted cyclopropane carbon atom bears a hydroxy group, the homoallyiic rearrangement leads preferentially to cyclobutanone derivatives (J. Sa-laun, 1974). Addition of amines to cydopropanone (N. J. Turro, 1966) yields S-lactams after successive treatment with tert-butyl hypochlorite and silver(I) salts (H.H. Wasserman, 1975). For intramolecular cyclopropane formation see section 1.16. 

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To summarize, gwi-dihalocyclopropanes may serve as starting materials for the preparation of cyclopropane and cyclopropene derivatives, they can lead to compounds with bicyclobutane and spiropentane structures, provide allenes and... 

Gem-Dihalocydopropanes belong to the most readily available cyclopropane derivatives known today. They have been shown to be extremely valuable starting materials for the preparation of cyclopropanes and cyclopropenes, they may be converted to bicyclobutane derivatives and spiropentanes, can lead to allenes and the higher cumulenes, cyclopentenes and cyclopentadienes, and many other classes of compounds, both hydrocarbon systems and derivatives with valuable functional groups. The article summarizes the preparative developments in the area of gem-dihalocyclopropane chemistry during the last decade. 

Strained unsaturated molecules such as methyl-enecyclopropane (356), bicyclopropylidene (357), and cyclopropene derivatives have been used as ligands. Remarkably, 356 and even 357 could be coordinated to give 358 and 359 in 72% and 83% yield, respectively, without opening of the strained cyclopropane rings (Scheme 65). The X-ray crystal structure analy-... 

Extensive studies involving the use of dirhodium catalysts for cyclopropanation and cyclopropenation reactions have been reported by Doyle [80], Davies [81], and Fox etal. [82] with chiral dirhodium(II) tetracarboxylates and their derivatives being the most common [83]. A large number of chiral dirhodium(II) carboxamidate complexes have been developed, primarily by Doyle et al, [60a] to perform asymmetric cyclopropanation [84] and cydopropenation [85] reactions. 

Addition of a rhodium carbenoid to an alkyne leads to a cyclopropene derivative. In an intramolecular context, the fused cyclopropene moiety is unstable and undergoes ring opening to generate a rhodium vinyl carbenoid entity, which can then undergo cyclopropanation or cyclopropena-tion, carbon hydrogen insertion, and ylide generation. This is illustrated... 

Acetylenes and cyclopropenes (37) are related to each other in the same formal way as olefins and cyclopropanes are. Recall that cyclopropanation of ethylene is almost slightly endothermic and the endothermicity was asserted to increase by some (3 2) kJ moT per alkyl group. Cyclopropanation of acetylene to form cyclopropene (37, X = X = H) is endothermic by (48.9 2.6) kJ mol. Cyclopropanation of propyne (monomethy-lacetylene) to form 1-methylcyclopropene (37, X = Me, X = H) has an increased endothermicity of (58.7 1.4) kJ mol. By contrast, the cyclopropanation of 2-butyne (dimethy-lacetylene) using a derived value for the enthalpy of formation of 1,2-dimethylcyclopropene (37, X = X = Me) has an accompanying endothermicity of only 41 kJ moT. We suspect that the last value is in error and so suggest remeasurement of the enthalpy of formation of dimethylcyclopropene as well as measuring the enthalpy of formation of other cyclo-propenes. ... 

When electron deficient alkenes are added to cyclopropene derivatives (74 equation 33) and (77 equation 34) in the presence of [Ni(COD)2], vinylcyclopropanes are formed in good yields. For example, dialkyl fumarate or maleate reacts with 3,3-dimethylcyclopropene in the presence of [Ni(COD)2] to give 2,3-bis(alkoxycarbonyl)-l-(2-methyl-l-propenyl)cyclopropanes (75), (76), (78) and (79), in which alkene stereochemistry is chiefly retained, in 50-73% yields. Reaction of methyl acrylate with 3,3-dimethylcyclopropene results in the formation of several products, while reaction of methyl acrylate with 3,3-diphenylcyclopropene gives vinylcyclopropane derivatives (80 equation 35) in 85% yield. Under similar conditions, methyl crotonate reacts with (74a) to give (82) in low yield (equation 36). Catalysis with nickel(0)/PR3, 2 [Ni(CO)4], 3 [Pd(DBA)2] or [Pd(DBA)2]/PlV33 gives mainly... 

The biosynthesis of cyclopropane and the related cyclopropene acids in higher plants has been studied by experiments with radioactive precursors. In this method, a supposed precursor for the compounds being studied is supplied to the plant and its incorporation into more complex molecules and/or conversion to products is studied at successive time intervals. The sequence in which the radiolabel appears in different compounds can be used to deduce the pathways by which they are made. Thus it has been deduced that oleic acid gives rise to the cyclopropane derivative of stearic acid (dihydrosterculic acid). The latter can either be shortened by... 

Addition to a carbon-carbon triple bond is even more facile than addition to a carbon-carbon double bond, and there are now several reports of intermolec-ular [71] and intramolecular reactions [72-74] that produce stable cyclopropene products with moderate to high enantioselectivities. One of the most revealing examples is that shown in Scheme 9 [72] where the allylic cyclopropanation product (30) is formed by the less reactive Rh2(MEPY)4 catalyst, but macrocy-clization is favored by the more reactive Rh2(TBSP)4 and Rh2(IBAZ)4 catalysts and, as expected, the highest enantioselectivities are derived from the use of chiral dirhodium(II) carboxamidate catalysts. 

Similarly, partially fluorinated and perfluonnated methylenecyclopropanes [87, 82], cyclopropenes [85, 84, 85], cyclobutenes [75, 86], and bicychc alkenes [87, 88, 89, 90] apparently derive dienophihc reactivity from relief of their ground-state strain during reaction Thus 2,2-difluoromethylenecyclopropane and perfluoromethylenecyclopropane undergo exclusive [2+4] cycloadditions [87, 82] (equations 72 and 73), whereas (difluoromethylene)cyclopropane undergoes only [2+2] cycloadditions [87]... 

Relevant examples of 1,2-dialkylcycloalkenes with which to test our conjecture about reaction 12 are disappointingly few. The simplest example of this class of compounds is 1,2-dimethylcyclopropene (24, n = 3, R1 = R2 = Me), and indeed, the requisite thermochemical data are available. Using the derived enthalpy of formation of 1,2-dimethylcyclopropene from Reference 56, we find this reaction to be 32 kJmol-1 endothermic. A posteriori, we are not surprised that this reaction is endothermic. After all, if it is part of the folklore of cyclopropanes that they are said to have olefinic character, then cyclopropenes are also said to have acetylenic character. Indeed, the related transalkylation reaction involving acetylenes... 

The elimination is successful with a range of substituents at C-2 or C-3 of the cyclopropane, although in some cases the derived cyclopropenes ring-open even at room temprature to give vinylcarbenes, which may be trapped in inter- or intramolecular processes. It is successful when X or Y = Br even if R = H, but when X = Y = Cl and R = H, an alternative 1,2-elimination of HC1 occurs. By careful control of the quantity of reagent, it is possible to carry out the elimination in the presence of functional groups which are relatively reactive to such reagents (final two examples below)112-118,120,80. 

The alkyne is formally derived by a 1,4-dehydrochlorination with ring opening, although subsequent work has shown that the cyclopropene ring-opens even at ambient temperature to 3-chloro-3-methylbut-l-yne and so a 1,2-dehydrochlorination of this is an alternative. The carbene could be formed by several routes from the cyclopropene, and an early experiment with a 14C-labelled compound indicated that the label at C-l of the cyclopropane became C-l of the carbene ... 

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