Methylenecycloalkanes, cyclopropanation

The introduction of carbenes and carbenoids into synthetic organic chemistry revolutionized the synthesis of cyclopropane derivatives21. In particular, cyclopropanation of methylenecycloalkanes became a very useful method for the preparation of SPC. Moreover, since cycloaddition of carbenes to olefins involves a very fast concerted process (i.e. it eliminates any intermediates during the formation of the three-membered ring)21, the method is equally efficient for the preparation of both unstrained and highly strained compounds. 

The Simmons-Smith reaction, which involves cyclopropanation by the Zn CH2I2 system (equation 6), is a very popular variant of this method22. However, an application of the Simmons-Smith reaction to methylenecycloalkanes often requires the use of high excess (up to ten equivalents) of the reagent, which complicates the workup and lowers the yields. 

Rhodium acetate catalyzed cyclopropanation of methylenecycloalkanes with diazocarbonyl compounds (equation 9) provides a direct method for preparation of functionalized SPC27. 

In this section we compare the enthalpy of formation of isomeric pairs of cyclic olefins, one with an exocyclic double bond and the other with the double bond endocyclic. We start with 1-methylcycloalkenes and related methylenecycloalkanes, species genetically 18a and 18b, respectively. From prior experience with cyclopropanes and the thermochemical consequences of replacement of sp3 carbons by sp2 carbons in three-membered rings52, we expect 1-methylcyclopropene to be considerably less stable than methylenecyclopropane because the former compound has two trigonal carbons within the ring while the latter has but one. And so it is found56 the former has a gas-phase enthalpy of formation 43.1 2.2 kJ mol-1 more positive than the latter. 

Although many recent improvements in the preparation of the Simmons-Smith reagent might be helpfuP , the authors of this chapter would recommend one to consider an alternative two-step cyclopropanation procedure, which includes cycloaddition of dichloro- or dibromocarbene to methylenecycloalkane followed by reductive dehalo-genation (equation if. The first reaction is usually carried under phase transfer conditions and presents a very simple and efficient procedure. Reduction of gem-dihalocyclopropanes with lithium in rerr-butanol or with sodium in liquid ammonia usually proceeds without complications and with high yield. 

A remarkable dependence of the reactivity on ring size has been found in the series of methylenecycloalkanes (Fig. 9) [106]. The exceptionally low rate constant for methylenecyclopropane indicates that the low solvolysis rates of cyclopropyl derivatives [154] are not only caused by the unfavorable change of hybridization of one ring carbon in cyclopropane but also by the low stability of the cyclopropyl cation relative to a compound with the same hybridization (methylenecyclopropane). The destabilization of the cyclopropyl cation must actually be greater than indicated by the numbers in Fig. 9 as the transition state of the electrophilic attack may already profit from the stabilizing ring-opening process (cf., Section III.B.2). 

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