Aldehydes, coupling with hydroxylamine

In 1999, Hajipour reported that silica gel, without any base, could be a useful catalyst for the preparation of oximes in dry media coupled with microwave irradiation. Hydroxylamine hydrochlorides were reacted with several aliphatic and aromatic aldehydes and ketones affording the desired oximes. 

Mukund Sibi of North Dakota State University has developed (J. Am. Chem. Soc. 2004,126,718) a powerful three-component coupling, combining an a,(5-unsaturated amide 9, a hydroxylamine 10, and an aldehyde 11. The hydroxylamine condenses with the aldehyde to give the nitrone, which then adds in a dipolar sense to the unsaturated ester. The reaction proceeds with high diastereocontrol, and the absolute configuration is set by the chiral Cu catalyst. As the amide 9 can be prepared by condensation of a phosphonacetate with another aldehyde, the product 12 can be seen as the product of a four-component coupling, chirally-controlled aldol addition and Mannich condensation on a starting acetamide. 

Scheme 16.1 Solid-phase synthesis of isoxazolidines according to the split-and-combine method, (a) Distribution of the resin into two equal portions, coupling of bromocarboxylic acids with N,N -diisopropyl-carbodiimide (D1C), combination of the resin, substitution with hydroxylamine. (b) Distribution of the resin into three equal portions, condensation with three different aromatic aldehydes to the corresponding nitrones, combination of the resin, (c) Distribution of the resin into three equal portions, cyclo-addition with three different dipolarophiles to isoxazolidines, combination of the resin.

Diamino-l/f-pyrunidine-2-thione was coupled with aromatic aldehydes (At = Ph, d-Cl-CeHt) to give the corresponding SchiffhasQS 20. Treatment of 20 with chloroacetic acid gave thiazolo[3,2-a]pyrimidine 21, which was condensed with j>-chlorobenzaldehyde to give compound 22. Compound 22 was condensed with hydroxylamine to give isoxazolo[4,5-J]thiazolo[2,3-a]pyrimidine 23 as shown in Scheme 9 [27]. 

Copper(II) acetate has been reported as a versatile catalyst for the transformation of aldehydes into primary amides with hydroxylamine. A route to dibenzoxazepinones from 2-iodobenzamides and 2-bromophenols has been reported to involve a copper-catalysed Ullmann coupling followed by a base-mediated Smiles rearrangement and ring-closing process (Scheme 104). " ... 

Kobayashi et al. found that lanthanide triflates were excellent catalysts for activation of C-N double bonds —activation by other Lewis acids required more than stoichiometric amounts of the acids. Examples were aza Diels-Alder reactions, the Man-nich-type reaction of A-(a-aminoalkyl)benzotriazoles with silyl enol ethers, the 1,3-dipolar cycloaddition of nitrones to alkenes, the 1,2-cycloaddition of diazoesters to imines, and the nucleophilic addition reactions to imines [24], These reactions are efficiently catalyzed by Yb(OTf)3. The arylimines reacted with Danishefsky s diene to give the dihydropyridones (Eq. 14) [25,26], The arylimines acted as the azadienes when reacted with cyclopentadiene, vinyl ethers or vinyl thioethers, providing the tet-rahydroquinolines (Eq. 15). Silyl enol ethers derived from esters, ketones, and thio-esters reacted with N-(a-aminoalkyl)benzotriazoles to give the /5-amino carbonyl compounds (Eq. 16) [27]. The diastereoselectivity was independent of the geometry of the silyl enol ethers, and favored the anti products. Nitrones, prepared in situ from aldehydes and N-substituted hydroxylamines, added to alkenes to afford isoxazoli-dines (Eq. 17) [28]. Addition of diazoesters to imines afforded CK-aziridines as the major products (Eq. 18) [29]. In all the reactions the imines could be generated in situ and the three-component coupling reactions proceeded smoothly in one pot. 

Haptens containing amino groups can be coupled directly to carriers containing carboxyl groups, or the amino group can be converted to a carboxylic acid by reaction with succinic anhydride. - When a keto or an aldehyde group is present in the hapten, it can be converted to a carboxyl via reaction with 0-(carboxymethyl)hydroxylamine or with hydrazides. Haptens containing double bonds can be made to react directly with mer-captoacetic or mercaptopropionic acid, or a two-step reaction may be performed bromination followed by reaction with mercaptocarboxylic acid. ... 

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