Hydrogen chloride with diazo ketones

In a first step, the carboxylic acid 1 is converted into the corresponding acyl chloride 2 by treatment with thionyl chloride or phosphorous trichloride. The acyl chloride is then treated with diazomethane to give the diazo ketone 3, which is stabilized by resonance, and hydrogen chloride ... 

The starting material in the synthesis of 106 (157) was 3-(3,4-dimethoxy-phenyl)propanoyl chloride, which with the aid of diazomethane at — 20°C, was converted to the diazo ketone 108. Treatment of 108 in ether with 48% hydrogen bromide gave 4-bromo-l-(3,4-dimethoxyphenyl)-3-pentanone (109). The bromo ketone 109 was heated in an autoclave with 2-iminotetra-hydropyran hydrochloride in methanolic ammonia and yielded the product 106, identical to the alkaloid cypholophine, in an overall yield of 6%. 

Diazo ketones give a-chloro ketones on treatment with hydrogen chloride (equation 9). Diazotiza-tion of a-amino acids in the presence of an excess of chloride gives a-chloro acids (Scheme 11). The configurational identity of the amino acids is lost with the achiral diazo intermediate. The reaction becomes useful in cases where the amino acid is easily available and the chloride is not. 

The mechanism of this reaction is only slightly more complicated than the usual reaction of nucleophiles with acid chlorides (p. 854). Diazo compounds are nucleophiles at carbon and add to the carbonyl group of the reactive acid chloride. Chloride ion is expelled in the elimination phase of this normal addition-elimination process. In the only new step of the reaction, chloride removes the newly acidic hydrogen to give the diazo ketone (Fig. 18.64).This hydrogen is acidic because the conjugate base is stabilized by resonance. 

The reaction232-235 (see also Ref. 236) of 1-diazoketones with hydrogen fluoride that affords 1-fluoro ketones has also been applied to carbohydrates, with, however, no success. Treatment of 3,4-di-O-benzoyl-1-deoxy-l-diazo-D-gfycero-tetrulose with hydrogen fluoride in ether mainly afforded 3,4-di-O-benzoyl-D-gfycero-tetrulose, whereas, with hydrogen bromide and chloride, 3,4-di-O-benzoyl-l-bromo-l-deoxy-and 3,4-di-O-benzoyl-l-chloro-l-deoxy-D-gfycero-tetrulose, respec-... 

A novel hydrogenation technique has been introduced, in which both catalyst and hydrogen are prepared in situ These investigations have also yielded highly active carbon-supported catalysts. Preferential reduction of diaryl ketones can be achieved by using lithium N-dihydropyridylaluminum hydride . Base-sensitive 0X0 compounds can be reduced to hydroxy compounds by a 3-step sequence through diazo compounds Enamines can be hydro-genolyzed to alkenes with lithium aluminum hydride and aluminum chloride... 

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