Heterosubstituted cyclopropanes

Heterosubstituted cyclopropanes can be synthesized from appropriate olefins and car-benes. Since cyclopropane resembles olefins in its reactivity and is thus an electron-rich car bo-cycle (p. 76ft). it forms complexes with Lewis acids, e.g. TiCL, and is thereby destabilized This effect is even more pronounced in cydopropanone ketals. If one of the alcohols forming the ketal is a silanol, the ketal is stable and distillable. The O—Si-bond is cleaved by TiCl4 and a d3-reagent is formed. This reacts with a -reagents, e.g. aldehydes or ketals. Various 4-substituted carboxylic esters are available from 1-alkoxy-l-siloxycyclopropanes in this way (E. Nakamura, 1977). If one starts with l-bromo-2-methoxycyclopropanes, the bromine can be selectively substituted by lithium. Subsequent treatment of this reagent with carbonyl compounds yields (2-methoxycyclopropyl)methanols, which can be transformed to /7,y-unsaturated aldehydes (E.J. Corey, 1975B). 

The starting materials have been prepared in good to high yields from a-hetero-substituted cyclopyllithiums and a-selenoaldehydes 31,35,77) (Schemes 60, 62, 63), or in a more convergent manner from 1-formyl-heterosubstituted cyclopropanes and phosphonium ylides31,35,45,77) (Schemes 61-63) or ot-seleno alkyllithiums31,138) (Schemes 59, 64). 

Heterosubstitution at nonactivated positions is also possible by using highly reactive metalating agents such as pentylsodium. When used in the presence of tm-BuOK, it readily and selectively forms vinylsodium derivatives that can subsequently be converted to organosilicium compounds.243 Norbomadiene and bicyclo-[3.2.0]hepta-2,6-diene are also readily silylated via the corresponding sodium compounds formed in the reaction with BuLi-rm-BuONa.244 Similar transforma-tions of strained polycyclic cyclopropanes were also achieved [Eq. (10.45) ] ... 

The allylmetallation of vinyl metals, y-heterosubstituted with a methoxy-methyl ether as the chelating group, leads to the corresponding gembismetal-lic derivatives,20 but now, warming the reaction mixture to room temperature promotes an internal nucleophilic substitution, leading to a metallated cyclopropane which can react with different electrophiles21 (Equation 7.5 and Protocol 9). 

Allylmetallation of y-heterosubstituted vinyl lithium derivatives and cyclopropanation reaction preparation of 1-(S )-iodo-2-(S M2-propenyl)-3-(R )-propylcyclopropane... 

Non-heterosubstituted organolithiums usually have low configurational stability, but the very rapid cyclisation of 49 means that - assuming tin-lithium exchange of 48 goes with retention - invertive substitution can be proved.51 Inversion at both nucleophilic and electrophilic centres is a common feature of cyclopropane-forming reactions.7... 

The method involving a-heterosubstituted cyclopropyllithiums and a-selenenylalde-hydes provides31,3S,77) quite exclusively the (E) stereoisomers of 1-heterosubstituted-1-vinylcyclopropanes after treatment of the l-(l-heterosubstituted)-l -hydroxy-2 -selenoalkyl)cyclopropanes with PI3/NEt3 (Schemes 60, 62b, 63 b). This implies that the two steps involved in the transformations are stereoselective (Schemes 60, 62b, 63b). The stereochemical result of the first step can be rationalized123 on the basis of the Cram-Karabatsos-Felkin rules124,125 and it is well-known that the synthesis of olefins from (P-hydroxyalkyl)selenides occurs by a formal anti elimination of the hydroxyl and selenyl moieties 4 9 11,12 123 163 . 

The very high nucleophilicity of a-heterosubstituted a-lithiocyclopropanes and of a-lithioalkyl selenides, even those bearing two alkyl groups on the, carbanionic center, permits the stepwise construction of a cyclopentane ring possessing several quaternary centers in vicinal positions with respect to one another by two successive ring expansion reactions from a suitably functionalyzed cyclopropane 135,224) (Schemes 98, 101). This feature has been used by Fitjer2240 for the synthesis of permethyl cyclobutanone, permethyl cyclopentanone, and even permethyl cyclohexanone, as well as for the preparation of previously unknown permethylcyclohexane. 

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