Amines oxidative cyanation

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... 

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... 

For best results the commercial triethylamine (Matheson, b.p. 89-90°) should be purified to remove primary and secondary amines and water, either by distillation from acetic anhydride and then from barium oxide, or by reaction with phenyliso-cyanate.5 2 3 4... 

Sn(OTf)2 can function as a catalyst for aldol reactions, allylations, and cyanations asymmetric versions of these reactions have also been reported. Diastereoselective and enantioselective aldol reactions of aldehydes with silyl enol ethers using Sn(OTf)2 and a chiral amine have been reported (Scheme SO) 338 33 5 A proposed active complex is shown in the scheme. Catalytic asymmetric aldol reactions using Sn(OTf)2, a chiral diamine, and tin(II) oxide have been developed.340 Tin(II) oxide is assumed to prevent achiral reaction pathway by weakening the Lewis acidity of Me3SiOTf, which is formed during the reaction. 

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). 

An important application of oxidation of a C-H bond adjacent to a nitrogen atom is the selective oxidation of amides. This reaction proceeds in the presence of ferf-BuOOH as the oxidant and Ru(II) salts. Thus in the example of Eq. (36), the a-tert-butylperoxy amide of the isoquinoline was obtained, which is an important synthetic intermediate for natural products [138]. This product can be conveniently reacted with a nucleophile in the presence of a Lewis add. Direct trapping of the iminium ion complex by a nudeophile was achieved in the presence of trimethylsilyl cyanide, giving a-cyanated amines as shown in Eq. (37) [45]. This ruthenium/peracid oxidation reaction provides an alternative to the Strecker reaction for the synthesis of a-amino acid derivatives since they involve the same a-cyano amine intermediates. In this way N-methyl-N-(p-methoxyphenyl) glycine could be prepared from N,N-dimethyl-p-methoxyaniline in 82% yield. 

Another key intermediate for pteridine synthesis was also seen in 2-amino-3-ethoxycarbonyl-5-phenylpyrazine 1-oxide which reacts with various amines to form the corresponding amides followed by cyclization with triethyl orthoformate giving 3-alkyl-6-phenyl-4(3/7)pteridinone 8-oxides <87JHC1109>. The synthesis of 2,4-diamino-6-methylpteridine 5-oxide (371) was achieved from 5-methyl-pyrazine-2-carboxamide (366) via the 4-oxide (367), a Hofmann degradation (368), bro-mination (369), and cyanation (370) followed by cyclization with guanidine to give (371) (Scheme 60) <93JHC841>. 

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