Cyclopropanes allyl

The search for the racemic form of 15, prepared by allylic cyclopropanation of farnesyl diazoacetate 14, prompted the use of Rh2(OAc)4 for this process. But, instead of 15, addition occurred to the terminal double bond exclusively and in high yield (Eq. 6) [65]. This example initiated studies that have demonstrated the generality of the process [66-68] and its suitability for asymmetric cyclopropanation [69]. Since carbon-hydrogen insertion is in competition with addition, only the most reactive carboxamidate-ligated catalysts effect macrocyclic cyclopropanation [70] (Eq. 7), and CuPF6/bis-oxazoline 28 generally produces the highest level of enantiocontrol. 

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. 

Two allyl cyclopropane-c s in equivalent amounts are actually observed to be formed. In the mercury sensitized decomposition of 5,5-dimethyl bicyclo [2.1.1] hexanone-2 (XXXI), the only cyclic hydrocarbons found are those derived from cyclopropane (38). 

Cyclopropanes can also be generated via decomplexation of cyclopropane containing allyl complexes of palladium. This reaction mode is represented by a palladium-catalyzed conversion of 1 -sulfonyloxy-1 -vinylcyclopropanes 6 or 1 -chlorovinylcyclopropanes, which, via nucleophilic substitution with allylic rearrangement, gave methylenecyclopropanes 7 with the heterofunction in the side chain.An allylic cyclopropane-containing palladium complex is suggested as the intermediate. -... 

In a similar fashion the three-membered ring in vinyl cyclopropane fragments was opened upon treatment with palladium(II) complexes to give n-allyl complexes. The reaction of (-t- )-car-2-ene with an equimolar amount of bis(acetonitrile)palladium(II) chloride in chloroform at room temperature produced a mixture of two isomeric complexes 8 and 9.>26-128 -phej]- formation can be rationalized by the attack of palladium at the allylic cyclopropane carbon and cleavage of either bond by the addition of chloride. When protic solvents such as alcohols or acetic were used the 0-nucleophile rather than the chloride was added to give 10 and 11. Analogous chloropalladination reactions have been reported for monocyclic systems. For example, formation of 12 and 13. ... 

A different type of sigmatropic reaction has been observed for a variety of acyclic alkyl substituted 1, 5-dienes. The reaction occur on direct irradiation and in competition with the [1, 3] sigmatropic shift, discussed earlier. The product of this rearrangement is an allyl cyclopropane and it arise by a [1, 2] sigmatropic shift. 

The allylic esters 189 and 191 conjugated with cyclopropane undergo regio-selective reactions without opening the cyclopropane ring. The soft carbon nucleophiles are introduced at the terminal carbon to give 190, and phenylation with phenylzinc chloride takes place on the cyclopropane ring to form 192[120]. 

Allylic acetates react with ketene silyl acetals. In this reaction, in addition to the allylated ester 468, the cyclopropane derivative 469. which is formed by the use of bidentate ligands, is obtained[303]. Formation of a cyclopropane derivative 471 has been observed by the stoichiometric reaction of the 7r-allylpal-... 

The cyclopropane bridge is formed only after hydrogen-atom migration. The driving force for this migration may be the fact that a more stable allylic radical results ... 

The landmark report by Winstein et al. (Scheme 3.6) on the powerful accelerating and directing effect of a proximal hydroxyl group would become one of the most critical in the development of the Simmons-Smith cyclopropanation reactions [11]. A clear syw directing effect is observed, implying coordination of the reagent to the alcohol before methylene transfer. This characteristic served as the basis of subsequent developments for stereocontrolled reactions with many classes of chiral allylic cycloalkenols and indirectly for chiral auxiliaries and catalysts. A full understanding of this phenomenon would not only be informative, but it would have practical applications in the rationalization of asymmetric catalytic reactions. 

In 1963, Dauben and Berezin published the first systematic study of this syn directing effect (Scheme 3.15) [37]. They found that the cyclopropanation of 2-cyclohexen-l-ol 32 proceed in 63% yield to give the syn isomer 33 as the sole product. They observed the same high syn diastereoselectivity in a variety of cyclic allylic alcohols and methyl ethers. On the basis of these results, they reasonably conclude that there must be some type of coordinative interaction between the zinc carbenoid and the substrate. 

Recently, Charette et al. have also demonstrated this behavior in the stereoselective cyciopropanations of a number of enantiopure acyclic allylic ethers [47]. The high degree of acyclic stereocontrol in the Simmons-Smith cyclopropanation has been extended to synthesis several times, most notably in the synthesis of small biomolecules. Schollkopf et al. utilized this method in their syntheses of cyclopropane-containing amino acids [48 a, b]. The synthesis of a cyclopropane-containing nucleoside was also preformed using acyclic stereocontrol [48c]. 

This chiral modifier provides one of the only methods for selective cyclopropa-nation of substrates which are not simple, allylic alcohols. In contrast to the catalytic methods which will be discussed in the following section, the dioxaborolane has been shown to be effective in the cyclopropanation of a number of allylic ethers [67]. This method has also been extended to systems where the double... 

Employing protocol V with the methanesulfonamide catalyst 122, a 93 7 er can be obtained in the cyclopropanation of cinnamyl alcohol. This high selectivity translates well into a number of allylic alcohols (Table 3.12) [82]. Di- and tri-substi-tuted alkenes perform well under the conditions of protocol V. However, introduction of substituents on the 2 position leads to a considerable decrease in rate and selectivity (Table 3.12, entry 5). The major failing of this method is its inability to perform selective cyclopropanations of other hydroxyl-containing molecules, most notably homoallylic alcohols. 

The next step in the calculations involves consideration of the allylic alcohol-carbe-noid complexes (Fig. 3.28). The simple alkoxide is represented by RT3. Coordination of this zinc alkoxide with any number of other molecules can be envisioned. The complexation of ZnCl2 to the oxygen of the alkoxide yields RT4. Due to the Lewis acidic nature of the zinc atom, dimerization of the zinc alkoxide cannot be ruled out. Hence, a simplified dimeric structure is represented in RTS. The remaining structures, RT6 and RT7 (Fig. 3.29), represent alternative zinc chloride complexes of RT3 differing from RT4. Analysis of the energetics of the cyclopropanation from each of these encounter complexes should yield information regarding the structure of the methylene transfer transition state. 

O Connor, S.P. Catalytic, Enantioselective Cyclopropanation of Allylic Alcohols PhD Thesis, University of Illinois, Urbana-Champaign, 1993. 

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