Acetalization 3-Acetamido ketones

Dakin, H. D. West, R. J. Biol. Chem. 1928, 78, 91, 745, and 757. In 1928, Henry Dakin and Rudolf West, a clinician, reported on the reaction of a-amino acids with acetic anhydride to give a-acetamido ketones via azalactone intermediates. Interestingly, one year before this paper by Dakin and West, Levene and Steiger had observed both tyrosine and a-phenylananine gave abnormal products when acetylated under these conditions.Unfortunately, they were slow to identify the products and lost an opportunity to be immortalized by a name reaction. 

In addition, iodine snccessfnlly catalyzed the electrophilic snbstitntion reaction of indoles with aldehydes and ketones to bis(indonyl)methanes [225], the deprotection of aromatic acetates [226], esterifications [227], transesterifications [227], the chemoselective thioacetalization of carbon functions [228], the addition of mercaptans to a,P-nnsatnrated carboxylic acids [229], the imino-Diels-Alder reaction [230], the synthesis of iV-Boc protected amines [231], the preparation of alkynyl sngars from D-glycals [232], the preparation of methyl bisnlfate [233], and the synthesis of P-acetamido ketones from aromatic aldehydes, enolizable ketones or ketoesters and acetonitrile [234],... 

Dakin-West reaction. Reaction of a-amino acids with acetic anhydride in the presence of base to give a-acetamido ketones. The reaction occurs via the intermediate azlactone. 

Anhydro-5-hydroxyoxazolium hydroxides are attacked by electrophiles at position 4 cf. 229). If this position is free, substitution ensues, as in the dimerization reaction of Scheme 21. Other examples are uncatalyzed acylations (equation 55) and diazo coupling (equation 56). The key step in the Dakin-West reaction, i.e. the formation of a-acetamido ketones from a-amino acids and acetic anhydride in the presence of pyridine, is acetylation of an intermediate betaine (230 Scheme 23). 

Although the method is well tolerating to the presence of free-amino, hydroxy, acetamido, ketone, and acetate ester groups, in several cases yields were rather low. Moreover, the strong deleterious effect of the ortAo-substituent to the halide was found, e.g. 2-iodotoluene and 2-iodopyridine were recovered quantitatively. Masuda s group has developed a similar method based on Pd(dba)2 / P(2-tolyl)3-catalysts suitable for electron-rich pura-substituted aryl iodides. The most serious side-reaction is the... 

It should be noted that there are several other means by which the key a-aminocarbonyl intermediates of the Gutknecht synthesis may be prepared besides by the reduction of a-oximino ketones. The oxidation of a-aminoalcohols, reduction of a-amino acids and their derivatives, hydrolysis of a-acetamido ketones formed from a-amino acids and acetic anhydride by the Dakin-West reaction, and the reduction of a-azido, a-diazo, and a-nitro ketones all lead to dihydropyrazines by way of a-amino ketones. The Gastaldi synthesis provides an alternate use of a-oximino ketones, to afford dicyano pyrazines. ... 

A mixture of the benzhydryl 3-chloromethyl-7-[(Z)-2-methoxyimino-2-(2-tritylaminothiazol-4-yl)acetamido]-3-cephem-4-carboxylate (1.50 g, 1.79 mmoles) and Nal (1.34 g, 8.93 mmoles) in methyl ethyl ketone (30 ml) was stirred at room temperature for 1 hour. After evaporation of the solvent the residue was dissolved in ethyl acetate (100 ml) and washed with water, aqueous Na2S203 and aqueous NaCI, dried and evaporated to give 7-[(Z)-2-ethoxyimino-2-(2-tritylaminothiazol-4-yl)acetamido]-3-iodomethyl-3-cephem-4-carboxilate (1.47 g, 89%) as an amorphous powder. 

In the ketose series, 5-acetamido-5-deoxypentuloses and 5-acet-amido-5-deoxyhexuloses can theoretically form hemiacetals having an acetamido group in the ring. However, as the tendency of a ketone... 

Hydroxylamine converts a 16a-bromoandrostan-17-one (216) cleanly into the 17-oxime (217) of the 16a-hydroxy-ketone,""" closely paralleling the action of hydrazine."" Reduction of the oxime-acetate (218) with diborane gave the 17/8-acetamido- 16a -acetoxy-derivative (219)."""... 

Condensation of oc-amino nitriles, in the presence of other aldehydes or ketones, gives rise to the direct formation of 5-(alkylimmo)-zl4-thiazoline-2-thiones (CLXVII) 85, 266, 343) (Table 25). Similarly acetamido compounds (CLXVIII (Table 26) are obtained, when the ring closure is carried out in acetic anhydride 85). 

Purpurosamine B (382), a seven-carbon atom sugar component of the antibiotic gentamicin C2, was synthesized from 6-acetyl-5,6-dihydio-2-methoxy-2H-pyran (333, R = Me). Oximation of the keto group, reduction of the oxime to the corresponding amine, and N-acetylation gave two stereoisomeric N-acet-amides. For further synthesis the erythro stereoisomer (380) was taken. Further steps involved the epoxldation of the double bond, isolation of the manno epoxide, and its reduction to methyl 6-acetamido-3,4,6,7-tetradeoxy-a-DL-araI)i>io-heptopyranoside (381). Oxidation of the 2-OH group, oximation of the ketone, and reduction of the oxime followed by acetylation gave methyl N,N -diacetyl-a-DL-purpurosaminide B, which was hydrolyzed to N,N -diacetyl-DL-purpuro-samine B (383). 

On treatment with sodium azide in aqueous acetic acid, the glycenosidulose (128) afforded a mixture of erythro- and /Areo-azido-ketones (129), which were separated after reduction (sodium borohydride) to ethyl 2-azido-2,3-dideoxy-a-D-n7>o-hexopyranoside and the corresponding D-/yxo-isomer. The r/Z>o-isomer was converted into JV-acetyl-lividosamine (2-acetamido-2,3-dideoxy-D-n 6o-hexose) (130) by a standard series of transformations. 

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