Heterocyclic /1-enamino esters and

A broad choice of heterocondensed uracils are easily and generally accessible from heterocyclic /3-enamino esters and isocyanates (01LA200 03LA341). The mixed urea intermediate is smoothly cyclized with 5% aq. NaOH the whole procedure can be carried out in a one-step reaction, when pyridine serves as solvent and base catalyst for the ring closure (68CB3377 85AHC299) (Scheme 11). 

The syntheses of simple 1,3-oxazines (74AG596 86G361) from acylated amino acids (86G361) by treatment with dihalotriphenylphosphorane and of heterocondensed l,3-oxazin-4-ones from several N-acylated heterocyclic /3-enamino esters (81CB3188) have been implemented by aza-Wittig reactions of heterocyclic 2-(triphenylphosphoranylidenamino)esters with acid halides. 

The easily accessible aroylaminoimidazole-4-carboxylates (228) give imi-dazo[4,5-d][l,3]oxazin-7-ones (229) in a novel cyclization with dichlorotri-phenylphosphorane (Scheme 85) (93S107). Heterocyclic )3-enamino esters, such as 5-amino-2-(methylthio)thiazole-4-carboxylates and 4-amino-2-(methylthio)thiazole-5-carboxylates can also be used in both cases 1,3-oxazine rings are smoothly condensed to the existing heterocyclic ring (93S107). 

Heterocondensed uracils are easily accessible from acyllactones, -lactams, -thiollactones (72S151), and heterocyclic /3-enamino esters, especially (85AHC299). The latter gives a broad range of novel types of condensed systems. With the aid of the hexamethyldisilazane trimethyl-chlorosilane (HMDS/TMSC1) technique or the use of NaH and halo-sugars, respectively, simple approaches have been developed to obtain unusual nucleosides [92JPR(ip)] (Scheme 15). 

A. Heterocondensed Uracils from Lactones and Heterocyclic /3-Enamino Esters... 

Similarly, (heterocyclic) /3-enamino esters substituted with an electron donor as well as with an electron acceptor group ( push-pull ) show a decreased cycloaddition tendency towards 1,3-dipoles such as azides see (yiCBSSio) and Section 4.11.4.7. 

While most classical enamines and open-chain enamino esters2 are obtained by condensation, e.g., of a secondary amine with a keto compound, heterocyclic /3-enamino esters can be obtained only by special reactions as, e.g., rearrangement or direct syntheses. Some of these are depicted in this section. 

In addition to several general reviews on enamine chemistry, all of which include heterocyclic syntheses, there is an extensive survey by Hickmott which is entirely concerned with the formation of heterocycles. More specialized reviews deal with heterocyclic enamines, enaminones, the photochemistry of enamides , heterocyclic jS-enamino esters , enamino thiones , the synthesis of indole alkaloids via enamines , formation of pyrimidines, pyridopyrimidines, pyridines and pyrrolizines from enamines , synthesis of lactams , formation of heterocycles from cyclic enamino ketones and 2-acetylcyclohexen-l-ones, the synthesis of 3-cyano-2(l -pyrimidine-thiones and -selenones from jS-enamino ketones and the chemistry of cyclic en-aminonitriles. ... 

Heterocyclic /J-enamino esters differ in many respects from enamines,2 open-chain /S-enamino esters,2 and heterocyclic enamines,3 all of which point to a specific electron distribution in their enaminocarbonyl chromophore. In the following, particular attention is paid to spectroscopic studies of these title compounds and to the consequences for their structures, protonation behavior, tautomerism, stability, and mesomeric forms. 

In Table II 13C-NMR data are given for a number of 4,5-dihydrofurans (Scheme 16).62 Schemes 17 and 18 present more 13C-NMR data of additional heterocyclic /J-enamino esters, which are, however, limited to unsaturated atoms C-2 and C-3.63 All of the enamino esters 68a-d, 69-72 show the common feature of a strongly electron deficient C-2, as in an amidine-C or a ketene-S, N-(-0,N-)aminal,65 while C-3 does not appear as an olefinic carbon... 

Although cycloadditions to enamines are well known,2 the partially saturated heterocyclic /J-enamino esters, as, e.g., 8, display only a very weak tendency toward cycloaddition reactions, and Diels-Alder-type (4 + 2) cycloadditions have not yet been observed. From the 1,3-dipoles known today,140 170 hr of treatment of the enamino esters 8 (X = O, n = 1) with... 

The reactivity of 2-amino-4H-pyrans as well as their chemical properties has been poorly studied because of their weak stability toward many reactants. They undergo ring opening and recyclizations in the presence of strong acids and bases, nucleophiles, and so on. But this feature can be turned to advantage in the synthesis of various heterocycles via recyclizations. Thus, the enamino moiety in 2-amino-4H-pyran-3-carbonitriles and 2-amino-4H-pyran-3-carboxylic esters provides access to diverse derivatives, including fused pyrans. The available data on the chemical properties of 2-aminopyrans are not systematic, and, in certain cases, are contradictory. 

Isothiocyanates normally act as weaker electrophiles and need more drastic conditions to give the thioxo derivatives 76 also organic bases, such as pyridine, have been successfully employed76 for the cyclization step, so that this heterocyclization procedure may be carried out as a one-pot, three-component (enamino ester, isocyanate, organic base) reaction. Higher car-bamoylated products, such as 109, are smoothly hydrolyzed in aqueous 5% KOH to the pyrido[2,3-d]pyrimidines 11076 (Scheme 26). 

Formamide is a powerful C-N-heterocyclization reagent. 2-Formamidino derivatives are intermediates. Robins transformed 3-aminopyrazole-4-carboxamide to a 4-oxopyrazolo[3,4-d]pyrimidine (155)95 by heating in formamide. In boiling formamide, 155 was obtained from ethyl 3-aminopyrazole 4-carboxylate (38)31 (Scheme 35). From the enamino ester 59 and formamide a 5,6,7,8-tetrahydrobenzo [b] thieno [2,3-d ] pyrimidin-4-one (156) was obtained,96 as well as the aromatic thionaphtheno[2,3-d]-pyrimidine (157).97 This heterocyclization method shows broad applicability... 

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