Solvent, protic, cyclopropanation

There had been no reports of catalytic cyclopropanation systems effective in aqueous or protic solvents until our report and the cobalt catalysts of Yamada and coworkers in 2001 [32]. Some of the Rh catalysts decrease their catalytic activity or decompose diazo compounds in the presence of water or alcohols giving alcohols or ethers [33]. In the case of copper catalysts, the free hydroxy groups on ligands do not interfere with the cyclopropanations [23,34]. 

Silver-initiated ring cleavage of bicyclo[1.1.0]butanes in protic solvents leads predominantly to mixtures of cyclopropanes and the corresponding dienes, e.g. a mixture of the norcarane ether 32 and the corresponding homoallylic ether 33 is observed in the reaction of 2,6-dimethyl-tricyclo[4.1.0.0 ]heptane (31) with silver perchlorate. This reaction is of little practical value for the synthesis of cyclopropane derivatives from bicyclo[1.1.0]butanes. 

A similar system with additional strain on the cyclopropane ring is quadricyclane. Its reaction with benzeneselanyl chloride in apolar solvents gave quantitatively addition products with preference for the formation of stereoisomeric 3-chloro-2-phenylselanylbicyclo[2.2.1]hept-5-enes 4 and 5. In polar or protic solvents such as acetonitrile, methanol or acetic acid, the competing opening of only one of the cyclopropane rings became dominant. The benzeneselanyl cation cleaved the most strained C — C bond in cyclopropane with concomitant or subsequent reaction with a nucleophilic solvent molecule. ... 

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. ... 

Zinc in a protic solvent has also been applied to the reductive ring opening of activated cyclopropane derivatives. Usually the most activated cyclopropyl bond was cleaved. Treatment of arylcyclopropyl aryl ketones 7 with zinc in ethanol alforded aryl propyl ketones in excellent yields. The reduction of 1,2-dibenzoylcyclopropane (7f) with zinc/zinc(II) chloride produced 1,3-dibenzoylpropane (81) in quantitative yield. Dimethyl 2-benzoyl-3-phenylcyclop-ropane-l,l-dicarboxylate (7e) was converted to the corresponding (2-benzoyl-1-phenylethyl)malonate (8e) when heated with zinc in methanol. ... 

Occasionally, gew-dichlorocyclopropanes with phenyl or alkoxy substituents are transformed by strong base in aprotic or (rarely) protic solvents to allylic substitution products that do not obey at all the rules for cyclopropyl to allyl rearrangements with regard to their constitution and configuration. "These reactions are mechanistically distinct. They are usually initiated by base-induced elimination of hydrogen chloride to form phenyl- or alkoxy-substituted cyclopropenes, which are then intercepted by nucleophiles. ° These reactions are discussed in Section 2.B.2.I. Small structural differences can divert the reaction into one or the other reaction channel. Cyclopropane 25 on treatment at — 50°C with 2 equivalents of potassium /er/-butoxide in tetrahydrofuran in the presence of catalytic dicyclohexano-18-crown-6... 

Reductive cleavage of strained cyclopropanes and cyclobutanes. Dekker et al. have reported reductive cleavage of some strained ring systems by zinc and zinc chloride in protic solvents as shown in the examples. The carbonyl groups are essential for this cleavage. No cleavage is observed in aprotic solvents (e.g., benzene). 

Cyclopropanations. A variety of electron-deficient alkenes react with this reagent In aprotic solvents to produce good 3delds of ethoxycarbonyTsubstItuted cyclopropanes (eq 1). EtOH and presumably other protic solvents allow alternative reaction pathways which seem to be dependent on proton transfer. The mechanism can be thought of as 1,4-addition followed by in tramolecular ring closure with loss of dimethyl sulfide. In general, the reaction succeeds for double bonds activated by one or two... 

The 4-methyl substituted 6/5-fused dienone If showed similar behavior to the parent 6/6-fused dienone, and gave the 5/6-fused hydroxy ketone 8b (R = H) in 59% yield upon irradiation in aqueous acetic acid and the related ethoxy ketone 8b (R = Et) upon irradiation in ethanol. However, the unsubstituted dienone le and the 2-methyl derivative Ig underwent additional photochemical rearrangements when irradiated in protic solvents. Thus, irradiation of le in methanohc acetic acid yielded the tricychc methoxy ketone 42, the 5/6-fused ketone 9e (R = Me) and the dienone 7e in ca. 3 3 2 ratio. Under similar conditions, photolysis of Ig gave 43 and 9g (as a ca. 9 1 mixture of C2 epimers) in a 5 8 ratio (Scheme 8). Compounds such as 9e, 9g, and 7e are rationahzed as resulting from cleavage of the internal bond of the cyclopropane ring in the mesoionic intermediate 4e or 4g (Scheme 1), while the tricychc ketones 42 and 43 would be formed through a pathway similar to that for ketone 16 (Scheme 3). ... 

Copper salts accelerate the decomposition and completely reverse the product distribution in favour of the cyclopropane derivatives. The solvent also seems to be of great importance in determining the product distribution. The ratio olefin-cyclopropane is increased by using solvents with higher dielectric constants". This phenomenon is illustrated by the decomposition of 4-(l-bromo-l-methylethyl)pyrazolines (87) ". In non-polar solvents both a cyclopropane (88) and an olefinic product (89) are formed (equation 18). In polar solvents, both protic and aprotic, the cyclopropane 88 is the only product observed. The rate of formation of 88 is very solvent dependent. A striking feature is a very strong acceleration rate in the cyclopropane formation with increasing solvent... 

The Bamford-Stevens reaction is the base-catalyzed decomposition of arenesulfonylhydrazones of aldehydes and ketones, leading to the formation of alkenes an or cyclopropanes. There are several important general reviews in this area of organic synthesis. Since the reactions are mostly carried out either in protic or in aprotic solvents, the reaction types are divided into the protic and aprotic Bamford-Stevens processes. This section reviews recent examples in the synthesis of alkenes and cyclopropanes from arenesulfonylhydrazones, which is closely related to the following Shapiro reaction. 

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