A Bronsted acid catalyzed method was developed for the synthesis of γ-cyanoketones from sulfonyl cyanides, olefins and ketones. The reaction is believed to proceed via intermediate formation of alkenyl peroxides by condensation of ketones with tert-butylhydroperoxide. These unstable compounds decompose by homolytic O–O bond cleavage, generating ketone-derived radicals which add to the olefins and generate the final products after reaction with the sulfonyl cyanide, thereby forming two new C–C bonds. A range of different ketones and olefins can be used, including steroidal ketones and simple alkyl olefins. The products can be further transformed to substituted lactones and piperidines, including a tetracyclic one. This reaction can thus be utilized to gain access to complex molecules from simple starting materials in only a few synthetic steps.

https://pubs.rsc.org/en/content/articlepdf/2019/QO/C9QO00447E

Radical addition of ketones and cyanide to olefins via acid catalyzed formation of intermediate alkenyl peroxides

1.

The oxidation of cyanohydrins by the S2O82−-Ag+ system begins with the reaction of the OH group of the cyanohydrin with silver ions, which results in the formation of 1-cyanoalkoxyl radicals. The sulfate ion-radicals practically do not take part in the direct oxidation of cyanohydrins.




2.

The initiation of the oxidation of cyanohydrins by peroxydisulfate in the absence of Ag+ ion proceeds via the cleavage of H atoms from the hydrocarbon groupings of the cyanohydrin by the sulfate ion-radicals. The 4(5)-hydroxy-4(5)-cyanoalkyl radicals, formed as a result of the 1, 4- and 1, 5-migration of the cyano group and subsequent oxidation, are converted to 5- and 6-cyanoalkanones. The oxidative rearrangement of alkanone cyanohydrins to 6-cyanoalkanones was observed for the first time.

Oxidative rearrangement of cyanohydrins with migration of cyano group: Mechanism of initiation by S2O8 2−-Ag+ system

1.

Alkanone cyanohydrins of general formula R(CH2)3CR'(OH)CN (R=H or alkyl, R' =alkyl) are efficiently oxidized by the system S2O82--Ag+ to 1-cyanoalkoxyl radicals, which then undergo a highly selective rearrangement, with successive migration of the H atom and CN group and oxidation to δ-ketonitriles RCH(CN)CH2CH2COR'.




2.

The cyanohydrins of 2-pentanone (Ia), 2-hexanone (Ib), 2-octanone (Ic), and 2-nonanone (Id) are oxidized by the system S2O82--Ag+ ∿4-18 times faster than tert-butanol, and in their oxidative ability they fall into the sequence: (Id) > (Ic) > (Ib) > (Ia).




3.

A new method was developed for the synthesis of the nitriles of 5-ketoalkanoic acids.

Ag + -catalyzed oxidation of alkanone cyanohydrins by peroxydisulfate ions: generation and reactions of 1-cyanoalkoxyl radicals

1.

The action of the S2O82−-Ag+ system on the cyanohydrins of cyclopentanone and 2-methylcyclopentanone leads to isomerization with opening of the cyclopentane ring and 1,5-migration of the cyano group and the formation of 5-cyano-substituted pentanoic and hexanoic acids.




2.

2-Methylcyclohexanone cyanohydrin under analogous conditions isomerizes with 1,6-migration of the cyano group to give 6-cyanoheptanoic acid, while cycloheptanone cyanohydrin undergoes 1,4-migration of the cyano group without ring opening to give 4-cyanocycloheptanone.




3.

Cyelopentanone and cycloheptanone cyanohydrins are oxidized ∼1.7 times more rapidly by the S2O82−-Ag+ system at 60°C than cyclohexanone cyanohydrin. The cyanohydrins of 2-methyl-substituted cycloalkanones are oxidized about twice as rapidly as their unsubstituted analogs.

Oxidative radical rearrangement of cycloalkanone cyanohydrins with 1,4-, 1,5-, and 1,6-migration of the cyano group

Acetophenone, butyrophenone, 1-indanone, and 1-tetralone are obtained by the oxidation of ethylbenzene, butylbenzene, indan, and tetralin by anNa2S2O8-AgNO3 system in water and in aqueous acetone.

Oxidation of alkylaromatic compounds by an Na2S2O8-AgNO3 system

1.

Alkanal cyanohydrins (ACH) of general formula R(CH2)3CH(OH)CN are oxidized by the system S2O82−Ag+ to the acids R(CH2)3COOH and NCCHRCH2CH2COOH, indicating the competitive conversion of the ACH in the initial stage of the reaction to 1-hydroxy-1-cyanoalkyl and 1-cyanoalkoxyl radicals.




2.

The oxidation of acetaldehyde cyanohydrin at 60° proceeds at approximately twice the rate of the oxidation of butanal, pentanal, isopentanal, and heptanal cyanohydrins, and approximately ten times as fast as that of tert-butanol.

D. S. Velibekova

Papers

Oxidative rearrangement of cyanohydrins with migration of cyano group: Mechanism of initiation by S2O8 2−-Ag+ system

Ag + -catalyzed oxidation of alkanone cyanohydrins by peroxydisulfate ions: generation and reactions of 1-cyanoalkoxyl radicals

Oxidative radical rearrangement of cycloalkanone cyanohydrins with 1,4-, 1,5-, and 1,6-migration of the cyano group

Oxidation of alkylaromatic compounds by an Na2S2O8-AgNO3 system

Ag+-catalyzed oxidation of alkanal cyanohydrins by peroxydisulfate