ACID CHLORIDES FROM a-KETO

Acetylenes, homologation to allenes, 63, 203 Acetylenes, in peptide synthesis, 63, 175 a,B-ACETYLENIC KETONES, ASYMETRIC REDUCTION OF, 63, 57 ACID CHLORIDES FROM a-KETO ACIDS, 61, 1 Acrolein [107-02-8], 62, 140... 

ACID CHLORIDES FROM a-KETO ACIDS WITH a,a-DICHLOROMETHYL METHYL ETHER PYRUVOYL CHLORIDE... 

Alternate Preparations Of a-Keto Esters From Acid Chlorides," Katritzky. A.R. Wang, Z. Wells, A.P. Org. Prep. Proceed. Int., 1995, 21, 457... 

Most of the conventional reagents for the synthesis of acid chlorides from carboxylic acids are unsatisfactory for the preparation of a-keto acid chlorides. For example, the reaction of pyruvic acid with phosphorus halides does not give pyruvoyl chloride7 whereas the use of phosgene8 or oxalyl chloride9,10 affords ether solutions of the acid chloride in low yield. Recently a useful preparation of pyruvoyl chloride from trimeth-ylsilyl pyruvate and oxalyl chloride has been described.11... 

Only one further chlorinative transformation of the keto function of 213 into the chloroolefine yields the certainly interesting optically active IR-cis-acid chloride 213 a of norchlorchrysanthemic acid 85. If these steps occur with high yield, then one should reckon with another effective and rather cheap pyrethroid in the next decade, this time from India. Reaction scheme 140 p. 72... 

Cobaltous chloride/potassium cyanide Homogeneous hydrogenation with cobalt complexes a-Amino- from a-keto-carboxylic acids... 

One year later, Tietze and co-workers (97BMC1303) presented a general and straightforward method for the synthesis of diverse polymer-bound -keto esters starting from acid chlorides and Meldrum s acid. One such resin-bound y3-keto ester, 43, was treated with hydrazine hydrate in THF to afford resin-ffee N-2-unsubstituted pyrazolone 44 in 84% yield (Scheme 13). In the same paper, the synthesis of a large number of 4,5-disubstituted 2-phenyl-2,4-dihydro-37/-pyrazol-3-ones was reported. 

P-Keto estersS F.thyl dilithiomalonate, prepared from ethyl malonate with n-butyllithium in THF containing a trace of 2,2 -bipyridyl (as indicator), reacts with acid chlorides at about —65° to give, after acidic work-up, / -keto esters. For highest yields at least 1.7 equivalent of the acid chloride is required. Reported isolated yields (nine examples) are 90-99%. 

Pyrazolinones and isoxazolinones are prepared from (3-keto esters and hydrazine or hydroxylamine by reactions such as (34 — 35) similar to those in (i) above. Diketene behaves as a masked (3-keto ester. Acetylenecarboxylic esters can be used in place of (3-keto esters to give pyrazolinones such as (36) and (37) and the corresponding isoxazolinones. (3-Chloro-a,(3-unsaturated acid chlorides react similarly (cf. 38 — 39). 

The ketocarbene is formed from 3-phenylpropanoyl chloride (dihydrocinnamic acid chloride) and diazomethane ring substituted dihydrocinnamic acids provide a route to substituted azulenes. Alternatively the keto group in (25) may be treated with a Grignard reagent for the introduction of alkyl substituents into the five-membered ring. 

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