Ketals, cyclopropenone

The product usually contains small amounts of ether, as judged by proton magnetic resonance. The yields given are based on pure cyclopropenone ketal. Proton magnetic resonance (chloroform-d) B (number of protons, multiplicity) 7.88 (2, singlet), 3.33 (6, singlet). 

Dimethyleneketene acetals 546 are easily available by a thermolytic rearrangement of methylenecyclopropanone ketals 544, in turn prepared from the corresponding cyclopropenone ketals [146a]. The thermolysis is a two-step process, involving the reversible formation of a dipolar TMM intermediate 545 [146b], followed by the irreversible production of stable 546 at higher temperature (Scheme 75) [145],... 

The first synthesis of a cyclopropenone was reported in 1959 by Breslowls who achieved the preparation of diphenyl cyclopropenone (11) by reacting phenyl ketene dimethylacetal with benzal chloride/K-tert.-butoxide. The phenyl chloro carbene primarily generated adds to the electron-rich ketene acetal double bond to form the chlorocyclopropanone ketal 9, which undergoes 0-elimination of HC1 to diphenyl cyclopropenone ketal 10. Final hydrolysis yields 11 as a well-defined compound which is stable up to the melting point (120—121 °C). 

The high reactivity of the strained double bond in cyclopropenes has led to several other more recent developments especially involving cyclopropenone ketals as substrates97. 

Alkoxy ally lie organozinc reagents react with the cyclopropenone ketal 78 and the major regioisomer is always the one in which the -carbon linked to the alkoxy group becomes... 

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). 

The first example of enantioselective allylzincation of an alkene was also reported for the cyclopropenone ketal 78 as substrate. The chiral allylzinc complex 135 was prepared from the corresponding bis-oxazoline derived from (,V)-valine by deprotonation with n-BuLi and transmetallation with allylzinc bromide. This reagent reacted with 78 and afforded the allylated product 136 with high optical purity ( = 99%) (equation 66)101. 

Allylzincation of the monosubstituted cyclopropenone ketal 137 with the chiral reagent 138 proceeded regioselectively so as to generate the less substituted secondary cyclo-propylzinc species 139. After hydrolysis, the resulting cyclopropanone ketal was obtained with high enantiomeric excess ( = 99%). The reaction was very slow at 20 °C but was considerably accelerated under high pressure (1 GPa) (equation 67)102. 

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). 

Diels-Alder reactions.1 This cyclopropenone ketal undergoes [4 -I- 2] cycloaddition with electron-deficient or electron-rich dienes at 25° when the reaction... 

PREPARATION AND THREE-CARBON + TWO-CARBON CYCLOADDITION OF A CYCLOPROPENONE KETAL CYCLOPROPENONE 1,3-PR0PANEDI0L KETAL... 

Studies have defined the scope of the thermal reactions of cyclopropenone ketals which are characterized by their thermal, reversible ring opening to provide reactive intermediates best represented as delocalized singlet vinyl carbenes, three-carbon 1,1-/1,3-dipoles without octet stabilization, (eq 2). 

Table I. Reactions of Cyclopropenone Ketal 1 with Electron-deficient Olefins... 

Eschenmoser s pyrone 38 on treatment with cyclopropenone ketal 39 in refluxing benzene afforded lactone 40 (73%). Lactone 40 on hydrolysis with acetic acid at 100°C afforded, after deprotection and decarboxylation, tropone 37 (70%). Introduction of the tropolonic hydroxyl group was achieved with hydrazine hydrate in ethanol, to give a mixture of deacetyl-colchiceinamides 41 (53%) and 42 (37%), followed by reaction with ethano-lic potassium hydroxide, which afforded tropolones 43 and 44, respectively. Tropolone 43 was converted to 44 which, therefore, became the major reaction product. Methylation of 44 gave a mixture of enol ether 18 and 45 which were separated by chromatography. 

S CONTENTS Introduction to the Series An Editor s Foreword, Albert Padwa. Preface, Dennis P. Curran. Intramolecular 1,3-Dipolar Cycloaddition Chemistry, Albert Padwa and Allen M. Schoffstall. Stereochemical and Synthetic Studies of the Intramolecular Diels-Alder Reaction, William R. Roush. Thermal Reaction of Cyclopropenone Ketals, Key Mechanistic Features, Scope and Application of the Cycloaddition Reactions of Cyclopropenone Ketals and p - Delocalized Singlet Vinyl Carbenes Three Carbon 1,1-/1,3-Dipoles, Dale L. Boger and Christine E. Brotherton-Pleiss. Index. 

Reactions of cyclopropenone ketal with terminal alkenes afford 1,4-divinyl ketone ketals in good yields (Eq. 51) [88]. 

Cyclopropenone ketals, of which cyclopropenone 1,3-propanediol ketal (1) is a representative and unusually stable example, have proven to be useful equivalents of the 1,3-dipole (i) in a regiospecific three-carbon + two-carbon cycloaddition with electron-deficient olefins, (eq 1). Table I shows representative results of a study of this reaction.7... 

In addition to the representative [3 + 2] cycloaddition reactions shown in Table I, the delocalized singlet vinyl carbenes have been shown to participate as tt2a components of non-Hnear cheletroplc [tt 2S + it 2a] cycloadditions to provided cyclopropanes with an observable endo effect, and asw2s components of [tt4s + i2s] cycloadditions with selected dienes to provide cyclo-heptadienes, (Scheme 1). This thermal reactivity of cyclopropenone ketals... 

F 2] Cycloaddition. The cyclopropenone ketal (1) (or 3,3-dimethoxycyclopro-pene) undergoes a thermal [3 + 2] cycloaddition w ith alkenes substituted by two electron-... 

Cyclopropenone ketals can undergo a similar [3 -I- 2] cycloaddition with aldehydes or ketones to provide butenolide ortho esters, which in turn can be converted into butenolides, furanes, or y-keto esters. ... 

CycloadditionJ Reaction of cyclopropenone ketals with alkenes bearing only one electron-withdrawing group results in unstable cyclopropane ketene ketals, which are not isolated, but rather are converted into m-disubstituted cyclopropanes by acid hydrolysis. 

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