Ring closure, decarboxylative

N-acylation, stereospecific addition, — cyclol ring closure, — decarboxylation, — rearrangement, — reduction, — ring closure, —... 

Isoxazoles (478) in the presence of base undergo ring opening to a-ketonitriles (479). When the reaction was carried out in the presence of hydrazines, 5-aminopyrazoles (480) were obtained. The reaction is also a convenient source of imidazoles, For example, when the 1,2-benzisoxazole (481) was treated with phenylhydrazine, decarboxylation initially occurred with subsequent ring closure to (482) (see Chapter 4.16). 

In cases where decarboxylation is anticipated, the quinazolinone could be obtained by heating ammonium o-formamidobenzoate or o-forra ami do benz amide for several hours. This ring closure could be effected more conveniently by boiling the o-formamidobenzamide with 3% aqueous sodium hydroxide for a few minutes, o-Amino-benzamides have also been converted to quinazolinones by refluxing with ethyl orthoformate alone or preferably in the presence of acetic anhydride. ... 

Application of the Bischler-Napieralski reaction to amides of tryptophan has been investigated. The cyclodehydration of acetyltrypto-phan under conventional conditions proved unsuccessful. Attempted ring closure of acetyltryptophan or its ethyl ester was accompanied by decarboxylation and aromatization, yielding... 

Another total synthesis used the rich chemistry of iminophosphoranes (95AHC159). The /3-(3-indolyl)vinyl iminophosphorane 354 underwent an aza-Wittig/electrocyclic ring closure reaction to give the carboline 355 which was hydrolyzed with lithium hydroxide (Scheme 106). A selective reduction, deprotection, decarboxylation and diazotation followed by ring closure gave Fascaplysine (353) (94TL8851). 

A completely different concept13 makes use of a highly reduced bilane 5 which is oxidatively cyclized to an isobacteriochlorin 6 with copper(II) acetate. The ring closure is initiated by ester cleavage with trifluoroacetic acid and decarboxylative formylation with trimethyl orthoformate to yield a dialdehyde. One of the aldehyde functions forms the desired methine bridge whereas the other is lost during cyclization. 

Alder/retrograde Diels-Alder reaction sequence of a diaryl alkyne with a 3,6-dicarbomethoxy tetrazine. The resulting diazine (14) is then reduced, cleaved and cyclized with Zn/acetic acid to the 2,3,4,5-tetrasubstituted pyrrole (15), which is then N-alkylated with a-bromo-4-methoxyacetophenone to give a pentasubstituted pyrrole (16). The synthesis of lukianol A is completed by ester hydrolysis, decarboxylation, ring closure and deprotection. 

Peroxidase and laccase enzymes were used to catalyze the decarboxylation of various tetrahydroisoquinoline-1-carboxylic acids to give high yields of the corresponding 3,4-dihydroisoquinolines (204). Compounds such as 125 (Scheme 29) are derived from Pictet-Spengler ring closure via a-keto acid and aryl amine condensation and are of biogenetic importance. The possible relevance of iso-... 

Another preparation employed the condensation of hydroxylamine with a substituted thiourea 239. In this example (Equation 30), no oxidation was required, since the central nitrogen atom is already in a higher oxidation state via its hydroxylamine derivative 240. Nucleophilic attack of the pyridine nitrogen atom resulted in ring closure, affording 241 accompanied by decarboxylation <2003S1649>. 

During the heating of /V-(2-carboxy-3-thienyl)aminomethylenemalo-nates (886, R = H, Ph) in boiling diphenyl ether (88EUP269295) or in polyphosphate [78JCR(M)4701, 78JCR(S)393], the ring closure was accompanied by decarboxylation to thieno[3,2-fe]pyridines (885, R = H, 2-Ph). 

Labeling experiments with l-deoxy-l-(dibenzylamino)-D-[l- C]-aruI>-mo-2-hexulosuronic acid [l- C] 112 indicated that the C label corresponded to the 5-methyl group of 111 (see Ref. 234). This is also consistent with a l-deoxy-2,3-dicarbonyl intermediate (115), and indicates that 111 is a decarboxylation product (see Scheme 22). The precise step entailing decarboxylation has not yet been determined. The carboxyl group could be carried through to ring closure (furanone formation). Such a step would provide a 2-carboxylate which is a /3-keto acid subject to ready decarboxylation. The labeling information and the initial steps of the mechanism in Scheme 22 are also consistent with the formation of 111 from D-[l- C]ribose and a secondary amine. ... 

NMR spectrum showing the presence of a 3-substituted pyridine with four nonequivalent methylene units in the substituent, and by its conversion to 2,3-bi-pyridyl with chloranil (26). Its synthesis was made by condensation of A -ben-zoylpiperidone (258) with ethyl nicotinate (259) followed by heating with concentrated hydrochloric acid, resulting in hydrolysis, decarboxylation, and ring closure (Scheme 18) 401). Application of the Mundy A-acyllactam rearrangement to A-nicotinoylpiperidone (261) has also led to a synthesis of anaba-seine (8) (Scheme 18) 402). 

Rhodium(II) catalyzed the addition of the carbene formed from methyl diazoacetoacetate, to the oxathiazolone (112 R = 4-MeOQH4) gives the 1,4,3-oxathiazine derivative (113) in low yield (6%), this probably proceeds through the intermediate sulfonium ylide (114), by decarboxylation and ring closure, either concominantly or sequentially (Scheme 14) <90JCR(S)343>. 

An interesting transformation of carbamoylaspartic acid (30a) or ethoxy-carbonylasparagine (30b) to uracil (31) was performed by electrochemical oxidative decarboxylation.77 The same ring-closure reaction occurs in a biological system via an enzyme-catalyzed oxidation. Good yields and mild conditions of the electrochemical transformations give promise of wide application [Eq. (34)]. 

Treatment of some substituted o-benzyloxy-ketones with hydrochloric acid in acetic acid gives, e.g., the carboxylic ester (130, R = COOMe), then the corresponding benzofuran (130, R = H) through debenzylation, ring closure, hydrolysis, and decarboxylation.331... 

The acids (244) on heating at 165°-170° in the presence of acetic anhydride and sodium acetate undergo decarboxylation and ring closure (the intermediate compound 245 being isolated or not according to the conditions) to benzofuran (246,562 R2 = R). 

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