Cyclopropanones and Cyclopropenones

Cyclopropanones deserve special comment, not because of their practical importance (they have no commercial value at this time), but because of their novel behavior and reactivity. No unambiguous synthesis of cyclopropanones was known prior to 1965, and the older textbooks usually contained statements such as cyclopropanones apparently cannot exist. However, they had been postulated as intermediates in various reactions (see, for example, the Favorskii rearrangement, Section 17-2C and Exercise 17-15), but until recently had defied isolation and identification. The problem is that the three-ring ketone is remarkably reactive, especially towards nucleophiles. Because of the associated relief of angle strain, nucleophiles readily add to the carbonyl group without the aid of a catalyst and give good yields of adducts from which the cyclopropanone is not easily recovered  

To avoid destructive side reactions, cyclopropanones have to be prepared at low temperatures in the absence of nucleophiles. A good example is the synthesis of cyclopropanone itself from ketene and diazomethane (see Section 16-4 A)  

When seemingly simple organic structures defy isolation, this usually stimulates many theoretical and experimental studies in an effort to rationalize anomalous behavior. In the case of cyclopropanone, the possibility was considered that the molecule might preferably exist as an open-chain dipolar structure rather than as the cyclic ketone  

Although the spectral properties of cyclopropanones and the easy formation of hydrates and hemiketals are inconsistent with the dipolar form, some reactions of cyclopropanones do indicate that the ring carbons are much more electrophilic than in other cyclic or acyclic ketones. For example, nucleophilic ring opening often occurs easily  

both [3 + 4] cycloadditions of cyclopropanone to dienes and [3 + 2] additions to carbonyl groups have been observed. These reactions seem easiest to understand if cyclopropanone can behave as if it had, or could be converted to, a dipolar open-chain structure  

---

Cyclopropanones and Cyclopropenones. The synthesis of indolizines and azaindolizines from diphenylcyclopropenone has been reviewed and the synthesis of 1-alkynyl cyclopropanols from cyclopropanone ethylhemiacetal has been improved upon. The reactivity of cyclopropenones and cyclopropenthiones towards nucleophilic reagents has provided practicable routes to heterocyclic ring systems only otherwise accessible with difficulty and the potential usefulness of such processes continues to be explored. The route from diphenylcyclopropenone (211) and alkyl-substi-... 

Cyclopropanones and Cyclopropenones. Treatment of cyclopropanone at low temperatures with ammonia followed by quenching with HQ affords the salt (228), the stability of which is ascribed to the quaternary nature of the nitrogen atom. Acid hydrolysis of 1-ethoxycyclopropyl isocyanate results in pure (228) in high yield, and... 

The carbonyl distances in diphenyl cyclopropenone and cyclopropenone (1.225/1.212 A) are larger than in cyclopropanone and indicate enhanced singlebond character. The same is true for the C=S bond in the thione 156 (1.63 A) compared to the C=S distance in thioketones (1.56 A1S7 ). 

For an unusual generation of the CC double bond in a cyclopropenone by double photoelimination of nitrogen from an a,a -his diazoketone, see Scheme 12 in Section 15.3. Examples of photoeliminations of CO from a cyclobutanedione (109) and a cyclobutenedione (112), to afford a cyclopropanone and a cyclopropenone, respectively, are given in Section 15.4. The latter reaction appeared to proceed by a two-step mechanism involving an initial ring opening. 

The isolation of cyclopropenones and their undoubtedly increased stability compared to the less-strained saturated cyclopropanones might well be attributed to the validity of the above symbolism of aromatic cyclopropenium contribution to the ground state of 7. It should nevertheless be clear, that the information available on the electronic structure of cyclopropenones demands certain refinements of this very useful qualitative concept. 

It is interesting to note that the C1=C2 distances in cyclopropenone and cyclopropene are nearly identical, whilst C1 2 —C3 is shorter in cyclopropenone. The opposite trends were observed for cyclopropanone-cyclopropane single-bond relationships. 

Bis(oxazoline) ligands have been shown to be useful in the many carbon-carbon bond-forming reactions previously listed. They have also been used in a myriad of other carbon-carbon bond-forming reactions. For example, Nakamura and coworkers used bis(oxazoline) ligands ent-2, ent-22, and ent-39 in ligand-induced enantioselective allylzincation. This reaction consisted of the transformation of the cyclopropenone acetal 198 into allylic cyclopropanone acetal 199 in yields ranging from 73 to 90% with selectivities from >98 2 for the isomer shown to 1 99 (Fig. 9.57). 

Addition of cinnamyl(mesityl)zinc to the C2 symmetrical cyclopropenone ketal 133 led to excellent diastereoselectivities with respect to the newly formed carbon—carbon bond (de = 97%) and induction from the chiral ketal (de = 91%). Deuteriolysis afforded the cyclopropanone ketal 134 in which three stereocenters have been generated99,10°. A product-like transition state model was proposed, in which the cyclopropene underwent considerable rehybridization and the zinc became preferentially attached to the less hindered equatorial olefinic carbon from the face opposite to the axial ketal methyl group (equation 65). 

Besides the activation of the olefinic partner by a metal, the unfavorable thermodynamics associated with the addition of an enolate to a carbon—carbon multiple bond could be overwhelmed by using a strained alkene such as a cyclopropene derivative286. Indeed, Nakamura and workers demonstrated that the butylzinc enolate derived from A-methyl-5-valerolactam (447) smoothly reacted with the cyclopropenone ketal 78 and subsequent deuterolysis led to the -substituted cyclopropanone ketal 448, indicating that the carbometallation involved a syn addition process. Moreover, a high level of diastereoselectivity at the newly formed carbon—carbon bond was observed (de = 97%) (equation 191). The butylzinc enolates derived from other amides, lactams, esters and hydrazones also add successfully to the strained cyclopropenone ketal 78. Moreover, the cyclopropylzincs generated are stable and no rearrangements to the more stable zinc enolates occur after the addition. 

The reaction with optically active hydrazones provided an access to optically active ketones. The butylzinc aza-enolate generated from the hydrazone 449 (derived from 4-heptanone and (,S )-1 -amino-2-(methoxymethyl)pyrrolidine (SAMP)) reacted with the cyclopropenone ketal 78 and led to 450 after hydrolysis. The reaction proceeded with 100% of 1,2-diastereoselectivity at the newly formed carbon—carbon bond (mutual diastereo-selection) and 78% of substrate-induced diastereoselectivity (with respect to the chiral induction from the SAMP hydrazone). The latter level of diastereoselection was improved to 87% by the use of the ZnCl enolate derived from 449, at the expense of a slight decrease in yield. Finally, the resulting cyclopropanone ketal 450 could be transformed to the polyfunctional open-chain dicarbonyl compound 451 by removal of the hydrazone moiety and oxymercuration of the three-membered ring (equation 192). 

Recently, the bicyclic cyclopropanones 78 and 79 were prepared in high yield by the Diels-Alder addition of cyclopropenone to the diphenyl-isobenzofuran 80 and the dimethylanthracene 57.62>... 

The procedures described herein illustrate the preparation of a substituted cyclopropenone acetal and an alkylidene cyclopropanone acetal.The latter compound has been used to generate a dipolar trimethylenemethane (TMM) species that undergoes [3+2] cycloaddition with electron-deficient 2p-electron C=C and C=X compounds. ... 

Possible pathways to the pyridopyridazinones are shown in Scheme 3. One route (path a) involves initial 1,3-dipolar cycloaddition of the JV-imine with the cyclopropenone and subsequent opening of the cyclopropanone ring with transfer of the amino hydrogen to afford 41. An alternate route (path b) is very similar to that proposed for the reaction with 2//-azirines (Section IV,A,6). 

Fig. 5.1 Geometry and coordinate axes assumed in calculations for ketones (X= ) and thiones (X=S) (a) cyclopropenone (cyclopropenethione), (b) cyclopropanone (cyclopropanthione), and (c) acetone (thioacetone)...

---