Cyclopropanation regioselectivity

Some straightforward, efficient cyclopentanellation procedures were developed recently. Addition of a malonic ester anion to a cyclopropane-1,1-dicarboxylic ester followed by a Dieckmann condensation (S. Danishefsky, 1974) or addition of iJ-ketoester anions to a (l-phenylthiocyclopropyl)phosphonium cation followed by intramolecular Wittig reaction (J.P, Marino. 1975) produced cyclopentanones. Another procedure starts with a (2 + 21-cycloaddition of dichloroketene to alkenes followed by regioselective ring expansion with diazomethane. The resulting 2,2-dichlorocyclopentanones can be converted to a large variety of cyclopentane derivatives (A.E. Greene. 1979 J.-P. Deprds, 1980). 

The Simmons-Smith cyclopropanation method has also found application for the a-methylation of ketones via an intermediate cyclopropane. The starting ketone—e.g. cyclohexanone 9—is first converted into an enol ether 10. Cyclopropanation of 10 leads to an alkoxynorcarane 11, which on regioselective hydrolytic cleavage of the three-membered ring leads to the semiketal 12 as intermediate, and finally yields the a-methylated ketone 13 ... 

Attempts to increase the diastereoselectivity by a more rigid cyclopropane backbone were not successful. However, the incorporation of racemic trans-cyclopropane carboxylate 35 is completely regioselective, and both diastereomeric products 36 were isolated in a ratio of 4.1 1 [39] (Scheme 23). 

Additions to cyclopropanes can take place by any of the four mechanisms already discussed in this chapter, but the most important type involves electrophilic attack. For substituted cyclopropanes, these reactions usually follow Markovnikov s rule, though exceptions are known and the degree of regioselectivity is often small. The application of Markovnikov s rule to these substrates can be illustrated by the reaction of 1,1,2-trimethylcyclopropane with The rule predicts that the... 

Negishi E, Tan Z (2005) Diastereoselective, Enantioselective, and Regioselective Carbo-alumination Reactions Catalyzed by Zirconocene Derivatives. 8 139-176 Netherton M, Fu GC (2005)Pa]ladium-catalyzed Cross-Coupling Reactions of Unactivated Alkyl Electrophiles with Organometallic Compounds. 14 85-108 Nicolaou KC, King NP, He Y (1998) Ring-Closing Metathesis in the Synthesis of EpothUones and Polyether Natmal Products. 1 73-104 Nishiyama H (2004) Cyclopropanation with Ruthenium Catalysts. 11 81-92 Noels A, Demonceau A, Delaude L (2004) Ruthenium Promoted Catalysed Radical Processes toward Fine Chemistry. 11 155-171... 

The same difference in regioselectivity holds for cyclopropanation with ethyl diazoacetate 25 K It is assumed that Cu(OTf)2 or Cu(BF4)2 are reduced to the Cu(I) salts by the diazo compound the ability of CuOTf to form stable complexes with olefins may then explain why, with these catalysts, cyclopropanation is governed by the steric environment around a double bond rather than by its electron-richness. 

The catalytic cyclopropanation of 1,3-dienes leads exclusively or nearly so to mono-cyclopropanation products, as long as no excess of diazocarbonyl compound is applied. The regioselectivity has been tested for representative rhodium, copper and palladium catalysts 59 7 ,72), and the results are displayed in Table 9. 

Several other examples of regioselective cyclopropanation of 1- and 2-substituted butadienes in the presence of copper catalysts are known (Scheme 5). 2-Trimethyl-siloxy-1,3-butadiene parallels the behavior of other 2-substituted butadienes (see Table 9) in that the electron-rich double bond is cyclopropanated 60. With the 1-methoxy-, acetoxy- or trimethylsilyloxy-substituted butadienes 17, 18 and 19, both double bonds are cyclopropanated, thus giving rise to sometimes unseparable mixtures of regio- and stereoisomers 79). Perhaps, the yields of separated and isolated regioisomers in some cases do not reflect the true regioselectivity as considerable... 

Table 9. Regioselectivities in the cyclopropanation of 1,3-dienes with EDA in the presence of various catalysts". The yields [%] of cyclopropanation at each of the double bonds are given"... 

Cu(OTf)2 is an intermediate case (Scheme 9). These findings parallel the catalyst s control over the regioselectivity of cyclopropanation with diazodiphenylmethane 47 (see Sect. 2.1). 

When the cis/trans stereoselectivity of cyclopropanation with ethyl diazoacetate in the presence of CuCl P(0-z-Pr)3, Rh6(CO)16 or PdCl2 2 PhCN was plotted against that obtained with Rh2(OAc)4, a linear correlation was observed in every case, with slopes of 1.74,1.04 and 0.59, respectively (based on 22 olefins, T = 298 K) S9). These relationships as well as the results of regioselectivity studies carried out with 1,3-dienes point to the similar nature of the intermediates involved in Cu-, Rh-and Pd-catalyzed cyclopropanation. Furthermore, obvious parallels in reactivity in the transformations of Scheme 45 for a variety of catalysts based on Cu, Rh, Fe, Ru, Re and Mo suggest the conclusion that electrophilic metal carbenes are not only involved in cyclopropanation but also in ylide-forming reactions66. ... 

An electron-releasing methoxy group enhances the regioselective insertion of platinum into a cyclopropane ring of 3 to form the complex 4, suggesting the stabilization of the incipient cation 5 with the methoxy group [6]. This result is in contrast to complexation to only the olefinic moiety of bicyclo[4.1.0] hept-3-ene under identical conditions. (Scheme 2)... 

The [Rh(CO)2Cl]2-induced ring fission of substituted cyclopropanes 8a-b affords the rhodium complexes 9a-b via carbonylation [8]. The regioselectivity of carbonyl group insertion depends on the substituent. Reduction with NaBH4 leads to the corresponding alcohol. (Scheme 4)... 

The study of substituted VCPs revealed that methyl substitution of the alkene gives the expected products and substitution of the cyclopropane gives, with high regioselectivity, the product shown in Scheme 80. 

Silaboration of bicyclopropylidene proceeds via proximal G-G bond cleavage at 130 °C in the presence of the palladium// r/-alkyl isocyanide catalyst (Equation (88)). In contrast to the aforementioned silaboration of methylene cyclopropanes, vinylsilane products are obtained with high regioselectivity.102... 

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