Amides anodic oxidation

Various nucleophiles other than methanol can be introduced onto the carbonyl carbon. Anodic oxidation of acylsilanes in the presence of allyl alcohol, 2-methyl-2-propanol, water, and methyl /V-methylcarbamate in dichlorometh-ane affords the corresponding esters, carboxylic acid, and amide derivatives (Scheme 24) [16]. Therefore, anodic oxidation provides a useful method for the synthesis of esters and amides under neutral conditions. 

In a related set of reactions, Oku and coworkers have been investigating the anodic oxidation of acyclic amides having alkoxy groups on the carbon alpha to the amide carbonyl (91) [61]. The direct... 

Using an identical process, the pipecolic acid derivative (112) was converted into a bicyclic amide derivative as shown in Scheme 36. In this case, the methoxylated amide proved to be unstable in the crude electrolysis reaction and was taken directly into the cyclization-ozonolysis sequence. A 74% yield of the bicyclic ketone was obtained over three steps. Compound (114) was converted into A58365B demonstrating that the anodic oxidation reaction allowed for rapid access to both natural products. 

Anodic oxidation reactions have also been used to functionalize substituted proline derivatives. For example, an anodic amide... 

Both anodic oxidation reactions proceeded well. As illustrated in Scheme 44, an anodic methoxylation of menthyl pyroglutamate followed by the trapping of an incipient A-acyliminium ion with allyl-silane in the presence of Lewis acid led to (138) [86]. While the stereoselectivity of this reaction was not high, the major product from the reaction could be fractionally crystallized from hexane and the route used to conveniently prepare (138) on a scale of 10 g. In this case, a platinum wire anode was used in order to keep the current density high. This was required because of the high oxidation potential of the secondary amide relative to the methanol solvent used in the reaction. 

The anodic oxidation utilized in the synthesis of (137) proved equally effective. In this example, the electrochemical step was used to functionalize the amide substrate (141) (Scheme 45) [87, 88]. A... 

Finally, it is important to note that many of the anodic reactions discussed above cannot be duplicated with traditional chemical oxidants. For this reason, the anodic oxidation of nitrogen-containing compounds represents a powerful class of reactions that has the potential to open up entirely new synthetic pathways to complex molecules. From the work already accomplished, it is clear that employing such an approach is both feasible and beneficial, and that the ability to selectively oxidize amines and amides is a valuable tool for any synthetic chemist to have at their disposal. 

Neutral aminyl radicals generated by anodic oxidation of lithium alkenyl amides undergo a stereoselective cyclization to cis-l-methyl-2,5-disubstituted pyrrolidines [249]. 

Much of the recent work on the use of anodic amide oxidation reactions has focused on the utility of these reactions for functionalizing amino acids and for synthesizing peptide mimetics [13]. For example, in work related to the cyclization strategy outlined in Scheme 3, the anodic amide oxidation reaction has been used to construct a pair of angiotensin-converting enzyme inhibitors [14]. The retrosynthetic analysis for this route is outlined in Scheme 4. In this work, the anodic oxidation reaction was used to functionalize either a proline or a pipercolic add derivative and then the resulting methoxylated amide used to construct the bicyclic core of the desired inhibitor. A similar approach has recently been utilized to construct 6,5-bicyclic lactam building blocks for... 

Finally, the intramolecular coupling reaction between an olefin and a pyrrole ring has been examined (Scheme 40). In this example, a 66% isolated yield of the six-membered ring product was obtained. A vinyl sulfide moiety was used as the olefin participant and the nitrogen protected as the pivaloyl amide in order to minimize the competition between substrate and product oxidation. Unlike the furan cyclizations, the anodic oxidation of the pyrrole-based substrate led mainly to the desired aromatic product without the need for subsequent treatment with acid. 

The anodic oxidation of substituted allenes [76-79] and hetero-allenes [80-85] has been extensively studied by Becker and coworkers. Oxidation of secondary and tertiary alkyl isothiocyanates resulted in an ot-cleavage processes [77]. Primary alkyl isocyanates yielded amides and carbonyl compounds due to the nucleophilic involvement of either acetonitrile or water [80]. Primary alkyl isothiocyanates 48 afforded five-membered thiadiazolidine 49 and 50 and... 

The anodic oxidation of amides and carbamates is one of the most general and efficient electrochemical reactions known [115]. The primary intermediate... 

OXIDATION OF ALCOHOLS, AMINES AND AMIDES Ni oxide anode O... 

Radical cations of 2-alkylidene-l,3-dithianes can be generated electrochemically by anodic oxidation using a reticulated vitreous carbon (RVC) anode <2002TL7159>. These intermediates readily react with nucleophiles at C-1. Upon removal of the second electron, the sulfur-stabilized cations were trapped by nucleophilic solvents, such as MeOH, to furnish the final cycloaddition products. Hydroxy groups <20010L1729> and secondary amides <2005OL3553> were employed as O-nucleophiles and enol ethers as C-nucleophiles (Scheme 50) <2002JA10101>. 

Ethers can be converted to acetals, and acetals to ortho esters, by anodic oxidation in an alcohol as solvent.194 Yields are moderate. In a similar reaction, certain amides, carbamates, and sulfonamides can be alkoxylated a to the nitrogen, e.g., MeS02NMe2 — Me-S02N(Me)CH20CH3.195 OS VII, 307. 

A number of related couplings have been reported during the synthesis of the alkaloid ( )-cryptopleurine149 and also intramolecular coupling of diaryl amides to dibenzazepine and dibenzazodne structures.150 A versatile method for the preparation of tetrahydroquinolines and jololidines has been developed.151 The method involves the anodic oxidation of AT,AT-dimethyl-aniline in methanol to afford a-methoxylated or a, a -dimethoxylated compounds and subsequent treatment of products with Lewis acids in the presence of olefins. 

Moeller has more recently contributed a series of reports describing the further use of this reaction in synthesis. Oxidation of the unsaturated amide 71 in methanolic acetonitrile afforded a substance 72 (equation 37) which could subsequently be converted into conformationally restricted peptide mimics99. Further, anodic oxidation of 73 resulted in intramolecular cyclization to afford 74 (equation 38), which could be converted into bicyclic reverse-turn peptidomimetics100. A similar intramolecular anodic cyclization of 75 into 76 (equation 39) was employed as the key step in total syntheses of the natural products (—)-A58365A and (+)-A58365B101. 

Imidazole carboxylic acids are readily converted into hydrazides,436 acid halides,437 amides,437-439 and esters,439-440 and they may be reduced to alcohols with lithium aluminum hydride,441 and to aldehydes by controlled potential reduction.442 Anodic oxidation of l-methylimidazole-5-acetic acid (94) using cooled platinum electrodes yields l,2-bis(l-methylimidazol-5-yl)ethane (95).443... 

As described in the previous section, the anodic oxidation of aliphatic amines is utilized only rarely in organic synthesis due to the instability of the generated intermediates, whereas amides tuid carbamates of aliphatic amines yield relatively stable intermediates which are sufficiently promising as starting materials in organic synthesis (equations 47 and... 

The products obtained by the anodic oxidation of amides or carbamates in methanol have the same structures as the compounds which can be synthesized from amides (carbamates), aldehydes and methanol (equation 50). l e regeneration of iminium cations from these a-methoxyamides and subsequent reactions of the iminium cations with nucleophiles such as active methylene compounds or nucleophilic aromatic nuclei is well known under the term amidoalkylation (equation 50). ... 

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