Cyclopropyl carbenoids

Chelation is another driving force that provides diastereoselective bromine-lithium exchange reactions to give cyclopropyl carbenoids. Thus, the exo-bromine atom in dibro-mocyclopropane 25 is exchanged exclusively due to the methoxy substituent, which encourages the lithium to occupy the cis orientation (equation 16) ° Several representative examples of cyclopropyl bromo lithium carbenoids obtained by bromine-lithium exchange reactions are given in Table 1. 

SCHEME 11. Electrophilic character of cyclopropyl carbenoids Reaction of 2,2-diphenylcyclo-propane with -butylhthium (2 equivalents)... 

Although Echavarren et al. reported similar conversions by platinum catalysis, lower selectivity was observed [165-167]. Computational studies then suggested the initial formation of a cyclopropyl carbenoid intermediate 213, as shown in Scheme 8.28. 

Creary, X., Jang, Z., Butchko, M., McLean, K. Silyl-substituted cyclopropyl carbenoids. Tetrahedron Letters 1996, 37, 579-582. 

Thomas E, Kasatkin AN, Whitby RJ (2006) Cyclopropyl carbenoid insertion into... 

A rationale for the heteroatom effect has recently been provided for the reaction of 1,6-enynes based on detailed mechanistic studies,318 314 especially DFT calculations performed by several groups (Scheme 90) 183>319321 From what has been disclosed so far, an interplay of cationic and carbenoid species is obvious in these processes. Nowadays, there is a good consensus to adopt the involvement of cyclopropyl metallacarbene intermediates. 

The discovery of carbene and carbenoid additions to olefins was the major breakthrough that initiated the tapping of this structural resource for synthetic purposes. Even so, designed applications of cyclopropane chemistry in total syntheses remain limited. Most revolve around electrophilic type reactions such as acid induced ring opening or solvolysis of cyclopropyl carbinyl alcohol derivatives. One notable application apart from these electrophilic reactions is the excellent synthesis of allenes from dibromocyclopropanes 2). 

Another feature of carbenoid-type reactivity is the cyclopropanation (reaction c). Again, this reaction does not only take place in vinylidene but also in alkyl carbenoids . On the other hand, the intramolecular shift of a /3-aryl, cyclopropyl or hydrogen substituent, known as the Fritsch-Buttenberg-Wiechell rearrangement, is a typical reaction of a-lithiated vinyl halides (reaction d) . A particular carbenoid-like reaction occurring in a-halo-a-lithiocyclopropanes is the formation of allenes and simultaneous liberation of the corresponding lithium halide (equation 3). ... 

Optically pure methylenecyclopropanes 59 were synthesized from cyclopropyl sulfones 58 and the carbenoid, iodomethylmagnesium chloride, in moderate to good yields (equation 15). ... 

Since the cyclopropanation reaction nsing zinc carbenoids is nsnally faster with electron-rich alkenes, it is not surprising to observe that enol ethers are nicely converted into cyclopropyl ethers in high yields (equation 17). ... 

Because of these and other useful molecules containing three-membered rings, methods to make them are important as well as interesting. Most chemical syntheses of compounds containing cyclopropyl groups make use of the addition of a carbene, or carbene equivalent, to an aikene. What do we mean by carbene equivalent Usually, this is a molecule that has the potential to form a carbene, though it may not actually react via a carbene intermediate. One such example is a zinc carbenoid formed when diiodomethane is reacted with zinc metal it reacts with alkenes just as a carbene would—it undergoes addition to the 7t bond and produces a cyclopropane. 

The reactivity of carbenoids is thus equally characterized by electrophilic [(a) and (c) in Scheme 1] and by nucleophilic behaviour (b). The variations of the groups R (H, alkyl, cycloalkyl, cyclopropyl, vinyl, heteroatoms) furnish a remarkable multiplicity. 

Enol ethers may also be cyclopropanated using zinc carbenoids stereoselectively. Furukawa cyclopropanation of enol ether 32 proceeds with high stereoselection, and the obtained cyclopropyl ether 33 can be easily transformed into the enantiomerically pure cyclopropyl alcohol 35 [30]. In this case, high stereoselectivity is achieved by employing the chiral diol 36, which is not commercially available. Using the commercially available enantiopure diol 37, the level of stereoselectivity is significantly lower (Scheme 7). 

The inherent energy content of the cyclopropane ring demands that the method of introduction of a cyclopropyl subunit itself relies either on highly reactive intermediates or on irreversible or energetically, if not entropically, favored processes. Thus the synthesis of cyclopropane derivatives can be classified into three major categories 1,3 bond forming sequences (equation 4) carbene or carbenoid routes (equation 5) and rearrangement pathways (equations 6 and... 

The procedures for the synthesis of cyclopropane derivatives, especially by the carbenoid route - " 49,55-57 Q, (ijg yjjjjg jQute (l.S-displacement), - have been amply reviewed. Equally well reviewed are the reactions of cyclopropanes and their use in synthetic methodologyFor the preparation of the more common cyclopropane derivatives, the use of suitably functionalized cyclopropyl building blocks that are commercially available would be recommended. 

Related insecticides include cypermethrin 7 (the corresponding dichloro derivative) and permethrin (where a-C is an unsubstituted CH2 group). Many other natural products containing the cyclopropyl group have been synthesized through related reactions of a carbenoid of copper or of rhodium with a carbon-carbon double bond see [11] for further examples. 

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