Carbamates, methoxylation

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. 

Scheme 24 N-a-methoxylation of carbamates and further conversion of the methoxy products.

Fig. 10 Regioselective anodic methoxylation of unsymmetrical carbamates using electroauxiliaries [36, 37].

Transformation of amines to aldehydes or ketones can be carried out via the anodic a-methoxylation of the corresponding carbamates, (4), followed by an acid-catalyzed conversion of the a-methoxylated... 

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. 

As described above, the carbon-carbon bond formation at the a-position of amines using anodically a-methoxylated carbamates as the starting compounds is highly useful for the synthesis of alkaloid type compounds, however, this method is limited only to the bond formation at the a-position. On the other hand, it has been found that the elimination of methanol from the a-methoxylated carbamates 47 yields the corresponding enecarbamates 48 in high yields 30). 

An oil bath temperature higher than 100°C results In the formation of unsaturated carbamate formed by the elimination of methanol from the methoxylated carbamate. Accordingly, in the anodic methoxylatlon of carbamates having high boiling points, the product must be purified by column chromatography in order to avoid formation of the unsaturated carbamates. 

This procedure describes anodic a-methoxylation of carbamates (2) which are derived from primary and secondary amines (1). ... 

The reaction mechanism of the a-methoxylation or a-acetoxylation of amides and carbamates" has been shown to involve direct one-electron removal from the lone pair electrons of the nitrogen atom in the initial step when inert supporting electrolytes are used. 

In the amidoalkylation, however, the preparation of the starting a-methoxyamides is often difficult since the reaction of aldehydes higher than formaldehyde is not necessarily successful, and even when formaldehyde is employed the yields and purities of the a-methoxyamides are not always satisfactory. On the other hand, the anodic a-methoxylation of amides and carbamates generally allows the synthesis of a-methoxyamides (carbamates) which caimot be prepared by the method describe by equation (50). 

Since anodically prepared a-formyloxy-A / -dimethylformamide has successfully been used as an electrophilic reagent, and it has been found that the a-methoxylation of the carbamates of a variety of higher aliphatic amines and alicyclic amines can be readily performed, extensive studies have been carried out to utilize the anodically synthesized a-methoxy- or a-acyloxy-amides and -carbamates as electrophiles in organic synthesis. One example is shown in equation (51). ... 

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. 

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... 

The anodic methoxylation of amides is not restricted to simple formic and AcOH derivatives, but has been performed also with peptides [Eq. (31)] [86], -substituted carbamates [87-90], and cyclic derivatives such as A-methoxycarbonylpyrrolidines [90,91], A-methoxycarbonylpiperidines [90,92-95], and oxazolidin-2-ones [96-98]. 

Anionic Fries carbamoyl transfer.1 Treatment of the biphenyl 2-O-carbamate 1 in which the ortho-position is protected by a methoxyl or triethylsilyl (TES) group with L.DA results in transfer of the carbamoyl group to form the biphenyl 2. Cyclization of... 

N-Homoallyl amides. A-acyl-a-methoxyamines (available from electrochemical methoxylation of amides and carbamates) are conveniently transformed to homo-allyl amines and /3-amino acids by replacement of the methoxy group. 

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 reaction-chemical reaction-electrochemical reaction-chemical reaction (ECEC) mechanism is well established for anodic methoxylation reactions of amines, amides, and carbamates. It was confirmed that the anodic methoxylation of fluoroal-Iq l sulfides also proceeds with by way of a typical ECEC mechanism as shown in Scheme 32. ... 

This procedure describes anodic a-methoxylation of carbamates (Z) which... 

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