Cyclopropanes alcohols

Figures 6.21 and 6.22 summarize our synthesis of plakoside A (161) and its diastereomer 161 in 2001.25,26 As I will describe later in this section, plakoside A was proved to be 161, not 161. Plakoside A (161) can be prepared from the three building blocks, A, B and C. D-Galactose will be the starting material for A, while B and C can be synthesized from cyclopropane alcohol D and L-serine or D-glutamic acid,...

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

Other by-products include acetone, carbonaceous material, and polymers of propylene. Minor contaminants arise from impurities in the feed. Ethylene and butylenes can form traces of ethyl alcohol and 2-butanol. Small amounts of / -propyl alcohol carried through into the refined isopropyl alcohol can originate from cyclopropane [75-19-4] in the propylene feed. Acetone, an oxidation product, also forms from thermal decomposition of the intermediate sulfate esters, eg. 

Hydrogen bromide adds to acetylene to form vinyl bromide or ethyHdene bromide, depending on stoichiometry. The acid cleaves acycHc and cycHc ethers. It adds to the cyclopropane group by ring-opening. Additions to quinones afford bromohydroquinones. Hydrobromic acid and aldehydes can be used to introduce bromoalkyl groups into various molecules. For example, reaction with formaldehyde and an alcohol produces a bromomethyl ether. Bromomethylation of aromatic nuclei can be carried out with formaldehyde and hydrobromic acid (6). 

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). 

The addition of nucleophiles to cyclic fluoroolefins has been reviewed by Park et al. [2 ]. The reaction with alcohols proceeds by addition-elimination to yield the cyclic vinylic ether, as illustrated by tlie reaction of l,2-dichloro-3,3-di-fluorocyclopropene Further reaction results in cyclopropane ring opening at the bond opposite the difluoromethylene carbon to give preferentially the methyl and ortho esters of (Z)-3-chloro-2-fluoroacrylic acid and a small amount of dimethyl malonate [29] (equation 8). 

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. 

Fig. 3.8 Cyclopropanation of styrene in the presence of alcohol ligands. [Yang, Z. Lorenz, ).C. Shi, Y. Tetrahedron Lett. 1998, 39, 8621. Reprinted with permission from Elsevier Ltd.)...

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... 

Another point for structural diversification is the sulfonamide group. Imai had already shown that a wide variety of groups could be introduced at this position to optimize the reaction. Since a wide variety of sulfonyl chlorides are commercially available, a number of different types of groups could be examined (Scheme 3.34). Testing of a variety of aryl and alkyl groups on the 1,2-cyclohexanediamine backbone demonstrates that the simple methanesulfonamide 122 is clearly superior or equal to many other analogs in the cyclopropanation of cinnamyl alcohol (Table 3.11). Another concern which was directly addressed by this survey was the question of catalyst solubility. 

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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