Unsaturated Cyclopropanes

Some years ago we began a program to explore the scope of the palladium-catalyzed annulation of alkenes, dienes and alkynes by functionally-substituted aryl and vinylic halides or triflates as a convenient approach to a wide variety of heterocycles and carbocycles. We subsequently reported annulations involving 1,2-, 1,3- and 1,4-dienes unsaturated cyclopropanes and cyclobutanes cyclic and bicyclic alkenes and alkynes, much of which was reviewed in 1999 (Scheme l).1 In recent days our work has concentrated on the annulation of alkynes. Recent developments in this area will be reviewed and some novel palladium migration processes that have been discovered during the course of this work will be discussed. 

One major advantage of the alkoxymercuration-demercuration approach to ethers over the acid-catalyzed process is the fact that carbon skeleton rearrangements are seldom observed. Only unsaturated cyclopropanes,42S>426 or aryl-substituted alkenes427 428 in the presence of highly electrophilic mercury salts afford rearranged products. 

Cyclopropanation of noncomplexed double bonds in the presence of complexed diene units within the substrate and decomplexation of the resulting acyclic or cyclic diene ligands, especially from tricarbonyliron complexes, is used in the synthesis of unsaturated cyclopropanes. The tricarbonyliron unit serves as a removable protecting group which allows regioselective cyclopropanation of the uncomplexed double bond. ... 

Cyclopropenyl systems can be formed from metallacyclobutadiene complexes. Here no decomplexation of unsaturated cyclopropanes is observed. The tungstacyclobutadiene complex 12 is converted into a cyclopropenyl complex 13 upon addition of a nitrogen nucleophile. ... 

Coordination chemistry of unsaturated cyclopropanes depends on the type and position of unsaturation. The chemistry of cyclopropenes (see Sections 2.B. and 2.C.) and methylenecy-clopropanes (see Section l.B.2.2.2. and l.B.2.4.1.1.)is described in other sections of this volume. 

Scheme 11.4. Unsaturated cyclopropanes and some of dieir reactions...

While analogous products are obtained by the Pd-catalyzed annulation of 1,3-dienes, this procedure may have advantages when the unsaturated cyclopropanes or cyclobutanes are more readily prepared. However, a large excess of alkenes was required. In 2004, they succeeded to extend their methodology to functionalized alkenes. Under the same reaction conditions, the corresponding annulated products were produced in moderate to good yields (Scheme 2.82b). 

Cyclopropane derivatives - have a band of variable intensity at 540-500cm (18.52-20.00 pm). An exception is that of vinylcyclopropane which has a strong absorption at 455 cm (21.98 pm), and other unsaturated cyclopropanes also have a medium-intensity absorption in this... 

Another widely used route to cyclopropanes involves the addition of sulfoniutn ylides to a,/3-unsaturated carbonyl compounds (S.R. Landor, 1967 R. Sowada, 1971 C.R. Johnson, I973B, 1979 B.M. Trost, 1975 A). Non-activated double bonds are not attacked. Sterical hindrance is of little importance in these reactions because the C—S bond is extraordinarily long... 

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). 

Intramolecular Friedel-Crafts acylations of olefins also give cycHc a,P-unsaturated cycHc ketones. Cyclopropane fused bicyclo[5.3.0]octenones, thus obtained, were used in the preparation of the marine sesquiterpenes, africanol [53823-07-7] and dactjlol [58542-75-9] (174). 

Cyclopropanes from unsaturaled carbonyl compounds via pyraaolines by catalytic pyrolysis... 

Pyrolysis at 190° of the resulting diastereomeric A -pyrazolines (8) and (11) leads to elimination of nitrogen and formation of the cis- and tmns-cydo-propanecarboxylates (9) and (12), respectively. Thermal decomposition of the A -pyrazoline (13) affords methyl tiglate (14) in addition to the cyclopropane derivative (15) in a ratio 2 1, while A -pyrazolines such as (3) give only 0L,[i- or, y-unsaturated esters, and no cyclopropane derivatives. 

The addition of diazomethane to a,/l-unsaturated ketones, e.g., benzalace-tone and benzalacetophenone, results in A -pyrazolines (16) which decompose thermally to the conjugated ketones (17). Cyclopropane formation is not observed in this instance. 

High vacuum pyrolysis, heating in organic bases, contact with acidic adsorbents and reaction at room temperature with perchloric acid or boron trifluoride etherate cleaves the pyrazoline to give a 45-60% yield of the cyclopropane derivative (13) as well as 9 % of the unsaturated methyl compound (14). ° ... 

In the presence of suitable a,/5-unsaturated carbonyl compounds (3) the nucleophilic methylide (2) undergoes conjugate addition followed by expulsion of dimethyl sulfoxide to give cyclopropanes (5). 

Thus the unsaturated ketones carvone, eucarvone and 1-acetyl-cyclohexane formed the cyclopropyl ketones (6), (7) and (8) while benzalaceto-phenone (9) affords l-benzyl-2-pheny 1-cyclopropane as a mixture of as and irons isomers (10) and (H) 233,234... 

In addition to unsaturated fatty acids, several other modified fatty acids are found in nature. Microorganisms, for example, often contain branched-chain fatty acids, such as tuberculostearic acid (Figure 8.2). When these fatty acids are incorporated in membranes, the methyl group constitutes a local structural perturbation in a manner similar to the double bonds in unsaturated fatty acids (see Chapter 9). Some bacteria also synthesize fatty acids containing cyclic structures such as cyclopropane, cyclopropene, and even cyclopentane rings. 

Epoxidation of aldehydes and ketones is the most profound utility of the Corey-Chaykovsky reaction. As noted in section 1.1.1, for an a,P-unsaturated carbonyl compound, 1 adds preferentially to the olefin to provide the cyclopropane derivative. On the other hand, the more reactive 2 generally undergoes the methylene transfer to the carbonyl, giving rise to the corresponding epoxide. For instance, treatment of P-ionone (26) with 2, derived from trimethylsulfonium chloride and NaOH in the presence of a phase-transfer catalyst Et4BnNCl, gave rise to vinyl epoxide 27 exclusively. ... 

Due to the high reactivity of sulfonium ylide 2 for a,P-unsaturated ketone substrates, it normally undergoes methylene transfer to the carbonyl to give the corresponding epoxides. However, cyclopropanation did take place when 1,1-diphenylethylene and ethyl cinnamate were treated with 2 to furnish cyclopropanes 53 and 54, respectively. 

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