Keto-O-heterocycles

Hydroxy-3-keto-0-heterocycIics. Startg. p-allenyl alcohol added to ca. 3 eqs. of a cold soln. of dimethyldioxirane in acetone, and reaction allowed to proceed until complete by t.l.c. ca. 10 min) -> 4-hydroxy-2,2-dimethyl-3-oxotetrahydropyran. Y 92%. a-Allenealcohols were similarly converted to furan analogs, while y- and 8-allenealcohols gave 2-(p-hydroxy-a-keto)-0-heterocyclics. F.e. with isolation of the intermediate spirodioxides, also 3-keto-O-heterocyclics with the addition of 0.5 eq. TsOH, s. J.K. Crandall, D.J. Ratal, Tetrahedron Letters 29, 4791-4 (1988). 

In the presence of a double bond at a suitable position, the CO insertion is followed by alkene insertion. In the intramolecular reaction of 552, different products, 553 and 554, are obtained by the use of diflerent catalytic spe-cies[408,409]. Pd(dba)2 in the absence of Ph,P affords 554. PdCl2(Ph3P)3 affords the spiro p-keto ester 553. The carbonylation of o-methallylbenzyl chloride (555) produced the benzoannulated enol lactone 556 by CO, alkene. and CO insertions. In addition, the cyclobutanone derivative 558 was obtained as a byproduct via the cycloaddition of the ketene intermediate 557[4I0]. Another type of intramolecular enone formation is used for the formation of the heterocyclic compounds 559[4l I]. The carbonylation of the I-iodo-1,4-diene 560 produces the cyclopentenone 561 by CO. alkene. and CO insertions[409,4l2]. 

O-tethered P-keto esters, through the intermediacy of aiylidene keto esters, have been efficiently utilized for the construction of immobilized dihydropyridines. Ceric ammonium nitrate (CAN) oxidation to pyridines followed by acidolytic cleavage provides a facile entry into nicotinic acid derivatives 57 [42], A three-component Biginelli cyclization of ureas on resin with a solution mixture of aldehydes and P-keto esters provides dihydropyrimidines 58 in high yield and purity [43], Heterocycles such as dihydropyridines and pyrimidines have historically proven to be a rich source of antimicrobial, antitumor, antiviral, and cardiovascular agents. 

Eicher T, Hauptmann S (1994) Chemie der Heterocyclen. Georg Thieme, Stuttgart Gilchrist TL (1992) Heterocyclic chemistry. Longman Scientific and Technical, Essex Takazawa O, Mukaiyama T (1982) New synthesis of (3-keto acetals. Chem Lett 1307-1308 Mukaiyama T, Hayashi M (1974) New syntheses of (3-alkoxy ketones and b-keto acetals. Chem Lett 15... 

The 1,3-dipolar cycloaddition of nitrile oxide to an unsaturated ester is a useful synthetic strategy for the synthesis of heterocycles such as A -isooxazolines and a-hydroxy-y-keto or y-imino carboxylic acids. Thus, the 1,3-dipolar cyclo-addition of the 4-0-acryloyl derivative 115 (R = f-butyldimethylsilyl) with two nitrile oxides (R = Ph or t-Bu) was explored by the Tadano group [95] (O Scheme 33). In the case of benzonitrile oxide (R =Ph), a functionalized A -isooxazoline 124 was obtained as a single isomer in excellent yield. Thus, the cycloaddition proceeded smoothly at room temperature with extreme stereoselectivity. 

One of the most common synthetic approaches to the construction of heterocyclic compounds involves the reaction of /3-keto esters with bifunctional nucleophiles. Thus a variety of reactions of (1) with different bifunctional heteronucleophiles, including hydrazine, substituted aminotriazoles, 2-aminopyridines, o-phenylenediamines, and o-aminothiophenol, lead to polynuclear condensed thieno compounds (e.g. 2-8) of potential medicinal interest featuring the pyrazolone, pyrimidinone, benzodiazepine, and benzothiazepine nuclei. Cannabinoid analogs can be prepared through cyclization of the condensation products of (1) with bifunctional oxygenated nucleophiles such as substituted resorcinols. ... 

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