Cyclopropanes substituents

In addition to siloxy- and alkoxy-substituted VCPs, alkyl- and H-substituted VCPs are also effective in the intermolecular [5 + 2]-cycloaddition reaction (Scheme 11). In general, an increase in the steric bulk of the cyclopropane substituent (H vs. Me vs. Pr1) leads to increased reaction rates, putatively through preferential population of the more reactive as-oid arrangement of the vinyl and cyclopropane moieties.43... 

Thermal rearrangement of 0-acyl Af-hydroxycarbamates carrying a cyclopropane substituent was reported (equation 255). When subject to flash vacuum thermolysis at 500 °C the carbamate 573 generates the Af-acyl imine 574 that rearranges to pyrroline 577 in 21-37% yield. The formation of a biradical intermediate 575 or a polar zwitterionic structure 576 was proposed. 

For cyclopropane, substituents at a single carbon might most effectively stabilize the antisymmetrical HOMO, whereas substitution at two carbons is expected to stabilize the symmetrical orbital. Since there is ample evidence for radical ions derived from the prototype of 2At symmetry (vide supra), cyclopropane radical cations with the alternative, antisymmetrical singly occupied (SO) MO appeared be of particular interest. We have identified two substrates, benzonorcaradiene (105) [229] and spiro[cyclopropane-l,9 -fluorene] (106), whose radical cations belong to this category [299, 300]. Interestingly, there is, as yet, no theoretical support for such species. 

Table 7 demonstrates that aromatic, aliphatic, and a, 3-unsaturated ketones or aldehydes can be used as electrophiles. With regard to the cyclopropane substituents, R1 has to be hydrogen for the synthesis of y-butyrolactones 200, but other examples (vide infra) show that the crucial C-C-bond forming step also proceeds with Rl H. 

Homoallylic nucleophilic substitution is known (equation 23), but its synthetic utility is hampered by competing direct substitution without opening of the cyclopropane ring. The product ratio is largely influenced by the nature of the attacking nucleophile and the cyclopropane substituents (steric effects). ... 

The syntheses of phenothrin analogues of lower insecticidal activity and of other chrysanthemate esters have been reported. Further pyrethroid papers concern the relationship between insecticidal toxicity and cyclopropane substituents in pyret-hroids, the photochemistry of the most potent known pyrethroid,and the metabolism of permethrin in rats (c/. Vol. 6, p. 13). " ... 

Recently, the stereochemical definitions of the addition of carbenes to C-C double bonds have been summarized. The term stereoselectivity refers to the degree of selectivity for the formation of cyclopropane products having endo vs. exo or, alternatively, syn vs. anti orientation of the substituents in the carbene species relative to substituents in the alkene substrate. The term stereospecificity refers to the stereochemistry of vicinal cyclopropane substituents originating as double-bond substituents in the starting alkene, i.e. a cyclopropane-forming reaction is stereospecific if the cisjtrans relationship of the double-bond substituents is retained in the cyclopropane product. Diastereofacial selectivity refers to the face of the alkene to which addition occurs relative to other substituents in the alkene substrate. Finally, enantioselectivity refers to the formation of a specific enantiomer of the cyclopropane product. 

Tetrasubstituted allenes with cyclopropane substituents, such as 198, react with CF2=CCl2 across the three-membered ring-substituted double bond to give the cycloadduct... 

For program SIMULA, the values of A, Zj, and corr are stored in tables. There are currently 39 basic carbon chemical shifts and 2479 values of for 150 substituents. Theoretically there are many more different values of Z for these substituents (e.g., the program now contains 467 out of a possible 600 for the alkane substituent, but only 39 of the 300 for the cyclopropane substituent), leading to some limitations, but largely in the case of the less common substituents. The tables of VODIK contain 22 basic proton shifts and the values of Zj for 85 substituents. 

The regiochemistry of the [2-l-2]-additions ofp- and m-substituted 6 was only affected by the substituents at the CC double bond of homobenzoquinones and not by the cyclopropane substituents, although the endo selectivity was appreciably reduced by the methoxy substituent. As a result, it is concluded that the spin density and the steric nature of the excited triplet state as well as the relative stability of the HH 1,4-biradical play a crucial role in the stereochemical course of these reactions. 

Osuka etaL described the type 11 photoreaction of various homonaphthoquinones 22a-d with abstractable y-hydrogens. The photochemical behavior of these substrates is very dependent on the cyclopropane substituents (R and R ). Irradiation of 22a (R = H, R = CH,) gave the usual cyclobutanol 23a along with the unsubstituted alcohol 24a (Scheme 14). The compound 24 may be derived by hydrogen transfer from a 8-carbon to the less reactive ketyl radical center of the primary biradical VII. It was confirmed that a photoequilibrium takes place between 22 and 23 via VII as a common intermediate. 

Cyclopropane rings are opened hydrogenolytically, e.g., over platinum on platinum dioxide (Adam s catalyst) in acetic acid at 2 - 4 bars hydrogen pressure. The bond, which is best accessible to the catalyst and most activated by conjugated substituents, is cleaved selectively (W.J. Irwin, 1968 R.L. Augustine, 1976). Synthetically this reaction is useful as a means to hydromethylate C—C double bonds via carbenoid addition (see p. 74f. Z. Majerski, 1968 C.W. Woodworth, 1968). 

Methylene transfer from lodomethylzmc iodide is stereospecific Substituents that were cis in the alkene remain cis m the cyclopropane... 

Chiral Alcohols and Lactones. HLAT) has been widely used for stereoselective oxidations of a variety of prochiral diols to lactones on a preparative scale. In most cases pro-(3) hydroxyl is oxidized irrespective of the substituents. The method is apphcable among others to tit-1,2-bis(hydroxymethyl) derivatives of cyclopropane, cyclobutane, cyclohexane, and cyclohexene. Resulting y-lactones are isolated in 68—90% yields and of 100% (164,165). 

Photochemically produced chloromethoxycarbene revealed ambiphilicity. Relative rates of cyclopropanation showed that electron donating as well as electron attracting substituents favor the reaction (Scheme 2) (79JA4736). 

The common side reaction in most thermal studies of fluorine-substituted cyclopropanes is difluorocarbene extrusion Increasing the number of fluonne substituents on the cyclopropane ring significantly increases the rate of difluorocarbene extrusion [135, 136, 137]... 

Disubstituted cyclopropanes exemplify one of the simplest cases involving stability differences between stereoisomers. A three-membered ring has no confonnational mobility, so the ring cannot therefore reduce the van der Waals strain between cis substituents on adjacent carbons without introducing other strain. The situation is different in disubstituted derivatives of cyclohexane. 

The powerful influence of an oxygen substituent on the rate and stereoselectivity of cyclopropanation augured well for the development of a chiral auxiliary based approach to asymmetric synthesis [54]. The design of the chiral auxiliary would take into account ... 

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 photochemical isomerization of 1,4-dienes 1, bearing substituents at C-3, leads to vinyl-cyclopropanes 2, and is called the di-n-methane rearrangement This reaction produces possible substrates for the vinylcyclopropane rearrangement. 

Cyclopropanes are now readily available and have become useful, through hydrogenolysis, for synthesis of compounds containing quaternary carbons, em-dialkyl, r-butyl, and angular-methyl substituents (779), compounds often available only with difficulty otherwise (.77,5i,55,750,756), Cyclopropanes can be formed in good yields by hydrogenation of cyclopropenes (26). 

Cyclobutanes are cleaved less readily than are cyclopropanes, but, nonetheless, hssion occurs without difficulty if the ring has additional strain UI3,I74b,I76), adjacent unsaturation 72b,J53a), or aromatic substituents... 

The coefficient of xV in the three expressions indicates that there exist four different derivatives of cyclopropane of the form (disubstituted cyclopropane with two identical substituents). Two of the four derivatives are mirror images of each other, that is, they form a pair of optical antipodes. If the spatial arrangement is disregarded, only two distinct cyclopropanes with formula are... 

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