Intramolecular reactions cyanide initiation

Formylbenzoic acid, potassium cyanide and anilines react in the presence of acetic acid to afford 3-amino-4-arylamino-isocoumarins (Scheme 215). The reaction proceeds via an initial Strecker reaction to form intermediate 786 followed by intramolecular attack of the carboxyl group onto the nitrile (Scheme 215) <2005EJ0817>. 

Quite often the products of the benzoin condensation are unstable to oxygen and lead to a-diketones. This is the case in intramolecular condensations when the initial product is an o-quinol, which is easily oxidized to the quinone. 4-Substituted tetramides can be prepared by the reaction of an aromatic aldehyde with oxalaldehyde in the presence of cyanide ion, via the benzoin condensation (Scheme 8). ... 

Synthetic use of the a-aminonitrile intermediates from the Strecker reaction have also been investigated.46 In this manner, it was possible to assemble the core scaffold of the indolizidine alkaloids 112. Treating 110, which contained the amine component and a dimethoxyacetal as a latent carbonyl component, with cyanide under acidic conditions initiated an intramolecular cyclization to afford the Strecker reaction intermediate a-aminonitrile 111. While one could hydrolyze the nitrile functionality to unmask a carboxylic acid, in this case, the nitrile was used to introduce the requisite sidechains needed in the construction of the indolizidine alkaloids 112. 

For example, sodium cyanide reacted with 5-ethoxy-3-ethyl-2-phenyloxazolium tetrafluoroborate 1065 in the absence of a dipolarophile and unexpectedly produced ethyl hippurate (Scheme 1.282). Mechanistically, they rationalized this result by initial addition of cyanide at C(2) to produce 1066. Ring opening of 1066 then generated the azomethine ylide 1067 that, in the S-conformation, undergoes intramolecular A-deethylation to yield the ketene acetal 1068 (not isolated). Chromatographic purification of the reaction mixture effected hydrolysis of 1068 with concomitant loss of HCN and C2H5OH to produce ethyl hippurate. 

Among a host of other phosphine-catalysed reactions in which the initial step is the formation of a reactive phosphoniobetaine intermediate by addition to a carbon-carbon double or triple bond are intramolecular cyclisations leading to benzobicyclo[4,3,0]-compounds, " cyclic ethers " and lactones,and a great many intermolecular reactions, e.g., a [3 -b 3]-annulation of modified t-butyl allylic carbonates and alkylidenemalonitriles to give cyclohexenes,phosphine- (and fluoride)- catalysed routes to 1,4-benzothiazepines from cyclic sulfenamides and alkynes, a [4- -3]-annu-lation of allylic carbonates with methyl coumalate to give functionalised bicyclo[3.2.2]nonadienes, the a-carbon addition of cyanide ion, generated in situ from cyanohydrins, to activated alkynes, and a stereoselective... 

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