Carbamates, methoxylation oxidation

Archer and co-workers (103) have also employed the Snieckus oxidative pho-tocyclization in the key step of their synthesis of the 7//-pyrido[4,3-c]carbazole ring system (Scheme 40). Thus, a Wittig condensation between pyruvate 242 and pyridine 243 gave the unsaturated ester 244. Photocyclization gave the tetracyclic ester 245. Reduction and reaction with methyl isocyanate led to carbamate 247. Oxidation of alcohol 246 to aldehyde 248, followed by a standard one-carbon homologation, gave the desired ethyl derivative 249. These chemists also synthesized the 10-methoxyl derivative of each compound. 

The reaction proceeds via electrogenerated cationic species as its seen with the nonfluorinated amines, carbamates, and amides (Scheme 6.14). However, the regiochemistry of this anodic methoxylation is not governed by the stability of the cationic intermediates B and B (thermodynamic control) since the main products are formed via the less stable intermediates B. Indeed, this remarkable promotion effect and unique regioselectivity can be explained mainly in terms of a-CH kinetic acidities of the cation radicals formed by one-electron oxidation of the amines since the stronger the acidity of the methylene hydrogen, the easier the deprotonation. 

Since the methoxyl group attached to the carbon adjacent to nitrogen can be readily replaced by various carbon nucleophiles, a-methoxylated carbamates are useful intermediates for the syntheses of nitrogen-containing compounds. The electrochemical oxidation of silyl-substituted carbamates provides a highly regioselective route to these useful compounds. 

The anodic oxidation of methyl N,/V-dialkylcarbamate in methanol, containing Et4NOTs, yielded three types of products a-methoxylated compounds, enamine-type products, and dealkylated carbamates.197 Methyl N-pyrrolidinylcarbamate (137), for example, gave on constant current oxidation... 

Anodic oxidation of A-benzyl-Ar-(a-silylmethyl)carbamate provides a-methoxylated product as a single regioisomer (equation 26), while the unsilylated parent carbamate gives a mixture of regioisomeric products (equation 27). Thus, the introduction of a silyl group can control completely the regiochemistry of the anodic methoxylation and can also activate the nitrogen atom toward anodic oxidation. 

In Scheme 8, five possible electrochemical pathways for the formation of V-acyli-minium ions are represented. Pathway a (see Sec. VIII.A) describes the direct anodic oxidation of amides and carbamates to the intermediated V-acylium ions via removal of one electron from the nitrogen lone pair followed by deprotonation in a-position of the nitrogen atom and further one-electron oxidation. In pathway b (see Sec. VIII.C), a decarboxylative methoxylation of an V-acylated amino acid (Hofer-Moset reaction) leads to the same intermediate. The radical that is formed after anodic decarboxylation is immediately further oxidized to the cation due to the electron donation of the nitrogen. Pathway c (see Sec. VIII.B) describes the anodic oxidation of an V-acylated amino... 

In contrast to anodic methoxylation of 2,2,2-trifluoroethylainines, //-(2,2,2-trifluoroethyl)carbamates do not undergo this oxidation reaction in methanol. However, the use of trifluoroethanol as the solvent or cosolvent with acetonitrile for this reaction leads to formation of a-methoxylated product 25 in high yield as shown in Eq. 63. The product 25 is useful as an a-aminotrifluoroethylating reagent in reactions with ketones and malonate esters. 

The electrochemical methoxylation of unsym-metrically substituted carbamates usually leads to formation of a mixture of two regioisomeric products Eq 3. However, the introduction of a sUyl group as an electroauxiliaiy controls the reaction pathway to bias the formation of the desired product Eq. 4 [6]. It is also noteworthy that the oxidation potential of a silyl-substituted carbamate is much less positive than that of the parent carbamate. 

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