Reductive cyanation

A one-step synthesis o( mtnles from carbonyls by a reductive cyanation with tosylmethyl isocyanide (TosMIC), also synthesis of 1,3-azole or of ketones... 

Reductive amination of carbonyl compounds, 59, 1 71, 1 Reductive cyanation, 57, 3 Redutive desulfonylation, 72, 2 Reductive desulfurization of thiol esters,... 

Reductive cyanation (5, 684 6, 600).1 The original conditions for conversion of ketones into nitriles give low yields when applied to aldehydes. Satisfactory results are obtained, however, if the initial reaction with TosMIC is conducted at 50° in DME before addition of methanol and reflux. Yields of 50-70% are then possible. 

This reaction can be extended to synthesis of alternating polyol chains found in polyene macrolide antibiotics. Thus reaction of the dibromide 5 with 2 equiv. of the cyanohydrin anion of 6 provides, after reductive cyanation, the protected polyol 7 in good yield. 

Side Note 17.8. Diazene anions have a key role in both the Wolff-Kishner reduction and its alternative, the Reductive Cyanation semicarbazone reduction (Formula D in Figure 17.67 and Formula G in Figure 17.68, respectively) they decompose into elemental nitrogen and an organometallic compound. The italics immediately explain what happens in the second step of the reductive cyanation of a ketone shown in Figure 17.69. 

Fig. 17.69. Two-step sequence for the conversion of a ketone into the homologous nitrile ("reductive cyanation of a carbonyl compound"). In the second step of the reaction the diazene anion G is generated and decomposes in a similar way as the diazene anion D in the Wolff-Kishner reduction of Figure 17.67 and the diazene anion G of the semicarbazone reduction in Figure 17.68.

Within the year a wide range of photoreactions in which an aromatic residue undergoes change in substitution has been published. As previously, the diversity of the various processes makes any classification of the reactions unrealistic, and so their order of presentation here is somewhat arbitrary. Aromatic photosubstitution reactions have been reviewed by Parkanyi although the treatment is not extensive, the processes of free radical, electrophilic, and nucleophilic photoinduced substitutions of arenes are well covered.Arene photoreactions initiated by electron transfer with electron donors or acceptors are the subject of a review by Pac and Sakurai. The requirements for the efficient photogeneration of the ion radicals are considered and the synthetic utility of the photoreactions, which include reduction, cyanation, and amination, is discussed. 

The reduction of cyanophosphates 46, readily prepared from ketones or aldehydes with diethyl phosphorocyanidate and lithium cyanide, led to nitriles in excellent yields [132] (Scheme 54). This reductive cyanation process has also... 

Titanium(IV) chloride-amines. I Reductive cyanation.. Aroi... 

Reductive cyanation. Aromatic ketones condense with aminoacetonitrile in the presence of TiCl4-Et3N. ot-Substituted arylacetonitriles are obtained upon treatment of the resulting imines with K2CO3 in refluxing DMF. 

Methods of preparation of selenocyanates are entirely analogous to those of thiocyanates, and the papers listed at the end of this section include examples of methods. The previously unknown compound PhTeCN is formed in only low yield from PhTeTePh and KCN, but in high yield through reductive cyanation of ArTeClj and by the general route from ArTeBr with KCN. ... 

Once again, new reagents for the direct conversion of aldehydes into nitriles have been reported,probably the most useful of which is the modified reductive cyanation procedure which now allows the preparation of nitriles from aldehydes with the addition of one C-atom (Scheme 20). An analogous procedure involves the reaction of potassium cyanide with the 2,4,6-tri-isopropylbenzenesulphonyl (trisyl) hydrazones of both aliphatic aldehydes and ketones (Scheme 21). 

The mechanism of action of the cyanation reaction is considered to progress as follows an oxidative addition reaction occurs between the aryl halide and a palladium(O) species to form an arylpalladium halide complex which then undergoes a ligand exchange reaction with CuCN thus transforming to an arylpalladium cyanide. Reductive elimination of the arylpalladium cyanide then gives the aryl cyanide. 

It has been shown52 that under similar conditions reduction of the nitrile groups in cellulose ethyl cyanate and of those in the copolymer of vinylidene cyanide with vinyl acetate, proceed simultaneously in two directions with the formation of aldehyde and amine groups. g+ g ... 

The iV-( -nitrophcnyl)pipcrazinc-2-carbonitrilc 251 (Y = NBOC) was reductively cyclized to the tricyclic /V-oxides 252 (Y = NBOC) either by catalytic hydrogenation, or by electrochemical reduction. Electrochemical reduction gave lower yield. Compounds 251 were prepared by electrochemical cyanation of the iV-(o-nitrophenyl)piperazine 250. The jV-oxides 252 were further hydrogenated to the 2,3,4,4 ,5,6-hexahydro-l//-pyrazino[l,2- ]quinoxaline 253 (Y = NBOC) (Scheme 46) <2001EJ0987>. 

To investigate the feasibility of employing 3-oxidopyridinium betaines as stabilized 1,3-dipoles in an intramolecular dipolar cycloaddition to construct the hetisine alkaloid core (Scheme 1.8, 77 78), a series of model cycloaddition substrates were prepared. In the first (Scheme 1.9a), an ene-nitrile substrate (i.e., 83) was selected as an activated dipolarophile functionality. Nitrile 66 was subjected to reduction with DIBAL-H, affording aldehyde 79 in 79 % yield. This was followed by reductive amination of aldehyde x with furfurylamine (80) to afford the furan amine 81 in 80 % yield. The ene-nitrile was then readily accessed via palladium-catalyzed cyanation of the enol triflate with KCN, 18-crown-6, and Pd(PPh3)4 in refluxing benzene to provide ene-nitrile 82 in 75 % yield. Finally, bromine-mediated aza-Achmatowicz reaction [44] of 82 then delivered oxidopyridinium betaine 83 in 65 % yield. 

Ene-nitrile oxidoisoquinolinium betaine 131 was readily prepared from vinyl triflate aldehyde 79 (Scheme 1.14). Palladium-catalyzed cyanation of vinyl triflate 79 with Zn(CN)2 in DMF at 60 °C produced ene-nitrile aldehyde 129 in 85 % yield [54]. Using the previously developed Staudinger-aza-Wittig reduction sequence, aldehyde 129 was coupled with cyclic ketal azide 121 to afford a 79 % yield of amine 130. The cyclic ketal amine 130 was then treated with 9 1 mixture of CH2CI2/TFA to provide ene-nitrile oxidoisoquinolinium betaine 131 in 93 % yield. 

In the same way, a benzodiazepine ring can be obtained after cathodic reduction of an anodically cyanated 2-nitrobenzyl tetrahydroquinoKne (Scheme 79) [115]. 

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