Amidation/redox amination

In the particular case of acrolein, which can be used both as a donor and acceptor component (3 equiv to nitrosobenzene), a novel domino amidation-redox amination took place under similar conditions (triazolium XII/DBU, CH Clj, rt), yielding A-propionyloxy-A-phenylacrylamide 54 as the major product (75%) [42]. In this reaction, as depicted in Scheme 5.36, two catalytic cycles seem to operate, one forming the Af-phenylhy-droxamic acid 53 by reaction of nucleophilic intermediate 135 (as d ) with nitrosobenzene. The second one operates through P-protonation of 135 (as d ) forming the activated ester 136, which then reacts with the hydroxamate of 53 yielding 54 along with NHC catalyst. 

SCHEME 5.36 Proposed domino amidation-redox amination of acrolein with nitrosobenzene. 

Rovis and Vora sought to expand the utility in alpha redox reactions to include the formation of amides [116]. While aniline was previously demonstrated as an efficient nucleophile in this reaction (Scheme 29), attempts to develop the scope to include non-aryl amines as various primary and secondary amines resulted in low yields. The discovery of a co-catalyst was the key to effecting amide formation (Table 15). Various co-catalysts, including HOBt, HOAt, DMAP, imidazole, and pentafluorophenol, are efficient and result in high yields of a variety of amides including those involving primary and secondary amines with additional functionality. 

Table 15 Amine scope of the redox amidation of a,a-dichloroaldehydes...

As previously explored by Bode, other a-reducible substrates, such as a,P-epoxy aldehyde and aziridinylaldehyde, are competent partners for redox reactions. (Scheme 33) [109], Various amines are compatible nucleophiles in this methodology in which P-hydroxy amides are furnished in good yield and excellent diastereose-lectivity. A similar reaction manifold was discovered concurrently by Bode and co-workers using imidazole as co-catalyst [117],... 

Alcohols and thiols also react rapidly with most amides to give alkoxide or thiolate ligands with liberation of amine. Steric factors can be sufficiently important to limit this exchange (e.g. equation 66) and in some instances redox reactions may occur (equation 67).212 Salt formation is also possible in some cases (equation 68).213... 

Oxidation-reduction (redox) reactions, along with hydrolysis and acid-base reactions, account for the vast majority of chemical reactions that occur in aquatic environmental systems. Factors that affect redox kinetics include environmental redox conditions, ionic strength, pH-value, temperature, speciation, and sorption (Tratnyek and Macalady, 2000). Sediment and particulate matter in water bodies may influence greatly the efficacy of abiotic transformations by altering the truly dissolved (i.e., non-sorbed) fraction of the compounds — the only fraction available for reactions (Weber and Wolfe, 1987). Among the possible abiotic transformation pathways, hydrolysis has received the most attention, though only some compound classes are potentially hydrolyzable (e.g., alkyl halides, amides, amines, carbamates, esters, epoxides, and nitriles [Harris, 1990 Peijnenburg, 1991]). Current efforts to incorporate reaction kinetics and pathways for reductive transformations into environmental exposure models are due to the fact that many of them result in reaction products that may be of more concern than the parent compounds (Tratnyek et al., 2003). 

Ritter et al. [147-155] have been studying side chain poiyrotaxanes. They synthesized side chain poiyrotaxanes by amide coupling of polymer-carrying carboxylic acid moieties with various semirotaxanes of methylated /l-CD(s) and an axle bearing an amine group at one end [147-154]. These works have been reviewed in an excellent review by Raymo and Stoddard [78]. Ritter et al. [155] reported recently a new type of side chain polyrotaxane. They polymerized inclusion complexes of di(meth)acrylates of butan-l,4-diol and hexan-l,6-diol with a-CD and with methylated /1-CD using a redox initiator system in aqueous media, and characterized the polyrotaxane structure by IR and glass-transition temperature measurements. 

A variety of R-NH2 locking reagents have been described, including primary amines, amine alcohols, nitriles, amides, and sulfonamides.67 tV-Substituents displaying multielectron redox activity have been described, including ferrocenylsulfonamide.68... 

Amsberry, K. L., Borchardt, R. T. Amine prodrugs which utilize hydroxy-amide lactonization. 1. A potential redox-sensitive amide prodrug. Pharm. Res. 1991, 8, 323-330. 

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