Cyclopropanones ring-closure

It seems necessary to accept an intermediate species with either zwitterionic or closely related character. The most recent proposal [2gg] invokes the known conformational features of the pregnan-20 0ne side-chain (p. 12). The individual steps are considered to be (i) formation of the i7a-bromoenolate anion (21) with the side-chain in its most stable conformation (ii) rotation about the C i7) C(20) bond to minimise dipole interactions between the i7a-Br and 20-oxygen substituents 22 (iii) expulsion of Br , perhaps assisted by the anti-perlplanar -0 entity to give the unsaturated epoxide (23) or its valence tautomer, the zwitterion 24) (iv) cyclopropanone ring closure and (v) base-promoted rupture to give the Favorskii product. 

In the initial step " the a-halo ketone 1 is deprotonated by the base at the a -carbon to give the carbanion 4, which then undergoes a ring-closure reaction by an intramolecular substitution to give the cyclopropanone derivative 2. The halogen substituent functions as the leaving group ... 

The molecular mechanisms for the ring openings of various cyclopropanone systems in the gas phase have been studied at the PM3 semiempirical level and shown to be disrotatory processes, while an experimental study of the stereomutation of 1,1-difluoro-2-ethyl-3-methylcyclopropane has confirmed the predicted preference for disrotatory ring opening and ring closure for this system. 

In other special cases, cyclopropanones have been prepared by photochemical rearrangements. For example, 9,9 -dianthracyl ketone (27) 32> and carbinol (28) 33> undergo ring closure to their respective... 

Cyclopropanone diselenoacetals 122 prepared by lithium diisopropylamide induced ring closure of 3-chloro l,l-di(methylseleno)- or 3-chloro-l,l-di(phenylseleno)-propane, have been transformed into the corresponding 1-selenocyclopropyllithium derivatives 123 upon treatment with n-butyllithium in THF at —78 °C. These intermediates have been trapped at —78 °C with aldehydes and ketones to produce the corresponding P-hydroxyselenides 124 in good yields, Eq. (37)66). 

Other chemists prefer a pericyclic description of the ring-closure step. The same enolate simply loses chloride to give an oxyallyl cation —a dipolar species with an oxyanion and a delocalized allylic cation. This species can cyclize in a two-electron disrotatory electrocyclic reaction (Chapter 36) to give the same cyclopropanone. We shall return to this discussion in the next chapter but, whatever the mechanism, there is no doubt that a cyclopropan one is an intermediate. 

The direct formation of a cyclopropanone cannot account for the reactions of lya-bromo- or 2i-halopregnan-20-ones [2g8,2gg,3oo7, for the concerted ring-closure could afford only... 

Because of their instability, cyclopropanones have been isolated in only a few cases, and methods for preparing the pure ketones are very limited. Among these are the addition of diazoalkanes to ketenes at low temperature ", potassium t-butoxide elimination of highly substituted a-bromoketones , photochemical decarbonylation of cyclobutane-1,3-diones " and ring-closure of 1,3-dihalo ketones Other methods exist for formation... 

The above considerations serve to explain why the C=0 bond is shortened while the C==C bond distance remains unaffected upon ring-closure of acetone and isobutylene to cyclopropanone and methylenecyclopropane, as shown in Figure 3. 

As expected, the influence of the halogen in a-halo ketones strongly influences the course of the reaction. At — 10°C, 2-chlorocyclohexanone reacted with pyrrolidine to give the isolable intermediate amino-substituted allylic chloride 6 (X = Cl) in 85% yield, along with 15% of bicyclic aminal. The corresponding a-bromo ketone showed the expected tendency for further ring closure into the cyclopropanone aminal 7, while a-fluorocyclohexanone was completely transformed into the allylic fluoride 6 (X = F). ... 

Concerning the mechanism of the Favorskii reaction, it is suggested that loss of the nucleofuge oecurs, resulting in a 2-oxyallyl cation, but that disrotatory ring closure is facile and the only products observed result from nucleophilic trapping of the cyclopropanone intermediate to provide cyclopropanols in fair to good yield. 

This looks as though each of the C—C bonds is independently the result of both HOMO/LUMO interactions, with an endo selectivity as well. In the presence of dienes, these species behave as allyl cations (see p. 259) and undergo clean [4 + 2] cycloadditions, as in the reaction of the oxyallyl 6.372 giving the tricyclic ketone 6.373, which is similar to the diene 6.369. Normally, oxyallyls are in equilibrium by disrotatory electrocyclic ring closures with cyclopropanones and with allene oxides, but the presence of the five-membered ring in these particular examples makes these pathways counter-thermodynamic. 

Cyclopropanone selenoketals such as (21 R = Ph or Me), which are prepared by ring-closure processes, behave normally when treated with BuLi in to give the corresponding a-lithio-selenides (22). These species are highly nucleophilic, but they are more basic than other selenium-stabilized carbanions. Enhanced nucleophilicity towards carbonyl compounds, at least for (22 R = Me), is observed by generating the carbanion in ether in this solvent, Bu Li (rather than Bu"Li) is required. The a-lithio-selenides (22) have been treated with a variety of simple electrophiles, such as aldehydes, ketones, and primary alkyl... 

The stereochemistry of the initial bromination turns out to be irrelevant as it disappears when the. > yallyl cation is formed. We know the stereochemistry of the final product so we know the stereochemistry of the cyclopropanone it must be on the opposite face of the five-membered ring to lie methyl group. The disrotatory closure of the oxyallyl cation goes preferentially one way with the H and CMe2Br substituents going upwards and the carbonyl group going down. 

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