Oxidative cyanation of tertiary amines

There is a primary alcohol-to-aldehyde step in the synthesis of (+)-batzelladine A, and it was suggested that the oxidation of the primary alcohol (1) with TRAP/ NMO/PMS/CH Cl proceeds through an iminium-Ru alkoxide complex (2), rearranging as in (3)-(4) to give the aldehyde (5) (Fig. 1.13) [101] (a similar mechanism was proposed for the Ru-catalysed oxidative cyanation of tertiary amines [403] cf. 5.1.3.4, Fig. 5.3). 

Recently, a new type of reaction - that is, aerobic oxidative cyanation of tertiary amines - was discovered. In this reaction, oxidation with molecular oxygen in place of peroxides, in addition to direct carbon-carbon bond formation by trapping of the iminium ion intermediates with a carbon nucleophile under oxidative conditions, is accomplished simultaneously. The ruthenium-catalyzed oxidation of tertiary amines with molecular oxygen (1 atom) in the presence of sodium cyanide gives the corresponding a-aminonitriles (Eq. 3.74) [132], which are useful for synthesis of a-amino acids and 1,2-diamines. 

Scheme 3 Ruthenium-catalyzed oxidative cyanation of tertiary amines with sodium cyanide...

Murahashi et al. [1] reported Ru(III)-catalyzed aerobic oxidative cyanation of N,N-dimethylanilines with NaCN in 2003, and the next year Li and co-workers developed an efficient Cu(I)-catalyzed alkynylation of tertiary amines with TBHP... 

Oxidation of (-amines in the presence of NaCN affords a-cyanoamines in 53-83% yield. Tertiary a-cyanoamines are known to afford iminum salts by loss of cyanide ion and this oxidative cyanation is used in a synthesis of the indolizidine... 

Photo-oxidation of l,l-dialkyl-2-arylhydrazines by single-electron transfer with trimethylsilyl cyanide (TMSCN) as cyanide ion source leads to regio- and stereoselective a-hydrazino nitriles. This stereoselective cyanation of hydrazines takes place on the more substituted carbon atom compared with the results obtained with tertiary amines (Scheme 5). 

Rueping et al. also developed separate conditions for the addition of phosphates, cyanide, and acetylides. Cyanations (or Strecker-type reactions) of THIQ derivatives were achieved using Ir(tbppy)2(bpy)PF6 (tbppy=2-(4-rert-bu1yl-phenyl)-pyridine 4) in acetonitrile and tertiary benzylic amines with potassium cyanide, in which the addition of acetic acid was crucial for HCN liberation and solubility. Product yields range from 81-97% (Scheme 10.7). In addition to THIQ derivatives, substituted anilines also underwent coupling, with allq l C-H bonds oxidized in preference to benzylic C-H bonds. 

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