Opening of cyclopropanes

The most frequently encountered examples of cyclopropyl ring opening reactions in the steroid field are usually associated with angular or side chain methylation sequences. In fact, isotope labeling of the C-19 angular methyl group is the only reported application of this reaction for deuteration or tritiation pui poses. 

Reductive opening of the cyclopropyl ring in 9j5,19-cycloandrostan-ll-one (234) has been achieved by treatment with a large excess of sodium in iso-propanol-OD. Analysis of the product for isotopic purity after oxidation to the corresponding ketone and base-catalyzed back exchange of the 9a-deuterium [(235) (236)] shows 19% do and 10% 62 isotopic impurities. The 10% 62 product is probably due to incomplete back exchange. 

Treatment of oc-cyclopropyl ketones with lithium in a mixture of N,N-d2 propylamine and hexamethylphosphortriamide is a recently reported method for deuterium labeling via reductive ring opening. This reaction provides y-labeled ketones in good yield (70-100%) and isotopic purity (85-93%). 

The conversion of tricyclo-[4,4,0,0]-decan-4-one (237) into the moiiodeutera-ted hydrindanone (238) serves as a good illustration of this labeling proce- 

Cleavage of cyclopropyl rings in the presence of an acid or base is illustrated by tlie tritiation of the 19-angular methyl group in 5, 19-cycloandrostane-3, 17-dione [(239) (240) R = T]. This reaction is carried out by heating 

---

From the point of view of the synthesis of dissonant systems the most important finding reported by Reissig [19c] is the opening of cyclopropanes by fluoride ion-induced desilylation to give carboxylic ester stabilised "homoenolate" anions, from which a series of 4-oxoalkanoic esters (21a ). with a 1,4-D relationship, were prepared (Table 5.6) ... 

Sarel and co-workers have examined some reactions of alkynylcyclopropanes with iron carbonyl compounds [1]. Treatment of cyclopropylacetylene (5) with iron pentacarbonyl under photolytic conditions gives, after cerium(IV) oxidation, isomeric quinones 6 and 7, derived from two molecules of 5 and two carbonyls with both cyclopropane rings intact [6]. Furthermore, the photoreaction of dicyclopropylacetylene (8) with iron carbonyl gives some ten different products depending on the reagents and the reaction conditions, and some of them have the cyclopentenone skeleton formed by the opening of cyclopropane ring coupled with carbonyl insertion [7] (Scheme 2). 

We began our calculations of the PES for the ring opening of cyclopropane in an attempt to resolve an apparent conflict between the results of experiments by Berson and co-workers and by Baldwin and co-workers. However, graduate students in our research group were among the experimentalists whose research ultimately benefited the most from the predictions made by our calculations. 

Calculations and Experiments on the Stereomutation of Cyclopropane. In 1965, Hoffmann published a seminal paper on trimethylene, another name for propane-1,3-diyl (8). He used extended hiickel (EH) calculations and an orbital interaction diagram to show that hyperconjugative electron donation from the central methylene group destabilizes the symmetric combination of 2p-n AOs on the terminal carbons in the (0,0) conformation of this diradical. Hoffmann s calculations predicted that the resulting occupancy of the antisymmetric combination of 2p-n AOs in 8 should favor conrotatory opening of cyclopropane (7), as depicted in Figure 22.8. 

Figure 22.8. Conrotatory ring opening of cyclopropane (7) to what Hoffmann called the (0,0) conformation of propane-1,3-diyl (8). The in-phase combination of Ip-n AOs in the LUMO is destabilized by an antibonding interaction with the re combination of C—H bonding orbitals at C2. A lower energy MO, which is not shown, is stabihzed by h3fperconjugative electron donation that is, the bonding version of this interaction. The out-of-phase combination of 2p-n AOs in the HOMO has a node at C2 hence, it does not mix with the C—H orbitals at this carbon.

With the conrotatory path a reasonable model for optical isomerization, and the EF(ts) mediated path a serviceable rationale for geometrical isomerization, the possible contribution of a disrotatory ring opening of cyclopropane did not receive full consideration. Yet its potential to contribute, and to complicate the situation, did not pass entirely un-noticed268. 

Although C—H insertion reactions rarely occur in intermolecular reactions with diazoacetates, these are common side reactions with diazomalonates3132 (equation 10) and diazo ketones (with a-allyl vinyl ethers).33 Several mechanistic pathways are available to generate the products of an apparent direct C—H insertion reaction and these include dipolar intermediates, ir-allyl complexes and ring opening of cyclopropanes.1 Oxidative problems due to the presence of oxygen are common with copper catalysts, but these are rarely encountered with rhodium catalysts except in systems where the carbenoid is ineffectively captured.34... 

Formation of a chromate ester is followed by the opening of cyclopropane, driven by attack of chloride and elimination of chromate anion. 

Nucleophilic opening of cyclopropanes doubly activated by alkoxycarbonyl groups is known to take place (see ref. 35 for a review). For instance, in an interesting study, Danishefsky, Dynak, and Yamamoto (36) showed the rapid base catalyzed (Na SOD in DMSO) interconversion of the two cyclopropanes 99 and 102 via their anions 100 and 101. Danishefsky, Tsai, and... 

Strained cyclic systems such as cyclopropane derivatives proved sensitive to silver ions. Indeed, silver usually induced ring opening of cyclopropanes, leading to argento cationic intermediates, which evolved further depending on substituents. Most, if not all, of these ring rearrangements resulted from initial formation of a a complex of the cyclopropane with silver ion. 

Whereas methyl 2-siloxycyclopropanecarboxylates are thermally stable up to temperatures as high as 170 °C, they readily rearrange at low temperatures under the influence of appropriate Lewis acids. Catalytic amounts (0.05-0.4 equiv.) of iodo-trimethylsilane within minutes to days promote a quantitative ring opening of cyclopropanes 755 to the corresponding silyl enol ethers 156 (Eq. 68, Table 4)88). 

The reaction mechanism involved the cyclisation of ketyl radical anion 3 on to the methylenecyclopropane moiety in a 5-exo-trig manner. Ring opening of cyclopropane intermediate 4 gave rise to the cyclohexyl radical 5, which then cyclised in a 5-exo-dig fashion to form the second ring (Scheme 6.2).5,6... 

The cleavage of a single bond (allylic or benzylic C-0 and C-N, C-X, C-S, N-N, N-O, 0-0 bonds, opening of cyclopropane, epoxides and aziridine by catalytic hydrogenation) is known as hydrogenolysis. Dehalogenation is favoured by basic conditions in the presence of a metal catalyst, Pd. The ease of dehalogenation decreases in the order I > Br > Cl > R... 

Acid-catalysed opening of cyclopropanes H. Laurent, H. Muller AND R. WiECHERT, B Y., 99 1966) 3836. 

SnCU is also effective in the opening of cyclopropane rings to produce cationic intermediates useful in cyclization reactions. For example, the cyclization of aryl cyclopropyl ketones to form aryl tetralones, precursors of lignan lactones and aryl naphthalene lignans, is mediated by SnCU (Eq. 60) [93]. The reaction is successful in nitromethane, but not in benzene or dichloromethane. Analogous cyclizations with epoxides result in very low yields (2-5 %). 

---