Cyclopropenones reactions with nucleophiles

This discovery represented an important advance in the synthesis of cyclopropenyl ions, since 18 can serve as a point of departure in the synthesis of a large variety of new cyclopropenyl salts by reaction with nucleophiles. This is discussed in the subsequent section of this chapter. The conversion of cyclopropenones to cyclopropenyl salts is similarly reserved for a later section. 

Finally, a reaction should be mentioned in which a nucleophile gives support to another reacting species without appearing in the final product. Diphenyl cyclopropenone interacts with 2,6-dimethyl phenyl isocyanide only in the presence of tri-phenylphosphine with expansion of the three-ring to the imine 344 of cyclobutene-dione-1,2229,230 Addition of the isocyanide is preceded by formation of the ketene phosphorane 343, which can be isolated in pure formss 231 it is decomposed by methanol to triphenyl phosphine and the ester 52. 

The nucleophilicities of cyclopropenone acetals", bromoketene acetals and an oxaphosphorane derivative, 26, are high enough to enable reaction with some Michael acceptors. Thus, cyclopropaneacetic esters (e.g. equation 88), cyclopropanecarboxylic esters, and 1-acetyl-1-methylcyclopropanes have been generated, respectively, from these precursors. 

The reactions of cyclopropenones with nucleophiles have been investigated extensively, with products arising from either conjugate addition or addition to the carbonyl group... 

Dimethyl-4,8-dioxaspiro[2.5]oct-l-ene is a synthetically useful precursor for cyclopropenones because of its stability and ready availability. The sodium derivative 1 of the cyclopropenone acetal in liquid ammonia reacted with alkyl halides giving alkyl-substituted cyclopropenone acetals 3. The lithiated cyclopropenone acetal 4 was generated by treating the cyclopropenone acetal with one equivalent of butyllithium in tetrahydrofuran. Reaction of the lithium carbanion 4 with alkyl halides proceeded cleanly in the presence of two equivalents of hexamethylphosphoric triamide (Table 1, entries 1-4). The lithium compound underwent nucleophilic addition to carbonyl compounds smoothly at — 70 C giving hydroxymethyl derivatives 5 (Table 1, entries 5-10). 

Reaction of 2-chloro-3-(2-chloro-l,l,2-trimethylpropyl)cyclopropenone (1) with various nucleophiles gave substituted cyclopropenones 2 in good yields. ... 

The addition of cyclopropenone 1,3-propanediyl ketal to electron deficient olefins produces cyclopentanone ketals 4,4,5-trisubstituted 3,3-[l,3-propanediylbis(oxy)]cyclopentenes 1 in 42-86 % yield with high regioselectivitv. Presumably diradicals or zwitterions are not involved as reactive intermediates, and the reaction starts with nucleophilic attack of the strained cyclopropene olefin onto the electron-deficient olefin2. 

A rather complex reactivity towards the cyclopropenone system is exhibited by N-nucleophiles. Thus, ammonia reacts with diphenyl cyclopropenone to yield either the enamino aldehyde 323222> or a mixture of the cis and trans isomeric diphenyl azetidinones 522223 depending on the reaction conditions these products result from primary addition of the nucleophile at C,(2 ... 

N-Heteroaromatic compounds like pyridine, pyridazine, pyrazine, isoquinoline, and their derivatives42,250 react with diphenyl cyclopropenone in a formal (3+2) cycloaddition mode to the C=N bond of the heterocycle. As expected from the results discussed earlier (p. 67), the reaction is initiated by attack of nitrogen at the cyclopropenone C3 position and followed by stabilization of the intermediate betaine 390 through nucleophilic interaction of the Cl/C3 bond with the activated a-site of the heterocycle, giving rise to derivatives of 2-hydroxy pyrrocoline 391—394). In some cases, e.g. diphenyl cyclopropenone and pyridine42, further interaction with a second cyclopropenone molecule is possible under the basic conditions leading to esters of type 392. 

The reaction of amines with cyclopropenones appears to be extremely sensitive to the reaction conditions Ammonia reacts with diphenylcyclopropenone at room temperature to yield the isomeric /3-lactams 56 and 57, whereas the vinyl aldehyde 58 is produced at — 33°C. These results can be rationalized in terms of the intermediate 59 which would result from conjugate addition of the nucleophile at carbon (equation 56). 

A superior route to these compounds using the condensation procedures involves the use of alkoxycyclopropenyl cations (equation 73) . These can be prepared readily by alkylation of cyclopropenones with trialkyloxonium tetrafluoroborates . This process can be extended to a large number of active methylene compounds if the conditions of the reaction are controlled carefully and the tertiary non-nucleophilic base diisopropylethy-lamine is used Otherwise, a large number of side reactions are observed. 

Although the reaction of 1,2-dichloro-3,3-difluorocyclopropene with thiocyanate leads simply to the replacement of the two chlorines by the nucleophile, reaction of the cyclopropene or of tetrachlorocyclopropene with sodium arylsulfinates gave an alkene in low yield (< 10%), apparently via the cyclopropenone, e.g. reaction of I. ... 

The reaction may proceed by nucleophilic substitution of the 1- and 2-halogens by sulfinate, followed by hydrolysis to the cyclopropenone and then ring opening of this with subsequent decarboxylation. 

Diphenylcyclopropenone and its thione are well known as highly electrophilic carbonyl compounds, which react with pyridine /V-acylimines to give l,3-oxazin-6-ones 39,46 166 and -6-thiones,46 respectively. The reaction of pyridine JV-imine with the cyclopropenone in methanol gives methyl 3-aminoacrylate 40.167 It is likely that these reactions involve ketene intermediates which are intercepted either by internal nucleophiles or by the solvent. Benzo[c]cinnoline JV-acylimines also give the oxazinones 39, whereas the Al-benzimidoylimines give stable 1 1 adducts as a result of a difference in the preferred site of attack by the electrophilic cyclopropenone (Eq. 22).168... 

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