Recent development in preparation reactivity and biological activity of enaminoketones and enaminothiones and their utilization to prepare heterocyclic compounds

Abstract

Enaminoketones and esters are gaining increased interest, particularly cyclic-β-enaminoesters, which are known as important intermediates for the synthesis of heterocycles and natural products, because the enantioselective preparation of highly functionalized compounds is of central importance in synthetic chemistry. Enaminones are versatile synthetic intermediates that combine the ambident nucleophilicity of enamines with the ambident eletrophilicity of enones. Enaminoketones and enaminonitriles have proven to be versatile building blocks for the synthesis of various heterocycles such as pyridine, pyrimidine and pyrrole derivatives. Enaminones systems have "enone" character, and may act as acceptors in both 1,2 and 1,4-additions. In this way the enaminone serves as a scaffold for annulation, and can gain access to systems such as pyrroles indolizidines, quinolizidines and perhydroindoles, all of which are common motifs in alkaloid structures. Enaminones are frequently employed as building blocks for the preparation of a variety of bicyclic compounds of biological interest and have been recently recognized as potential anticonvulsant compounds. Since a large number of developments in the use of enaminones in heterocyclic synthesis have occurred, a review of the recent developments in the synthetic approaches, covering the literature since 1995 until 2004, to these interesting molecules and their useful chemical transformations and biological activity can be considered of considerable value.J. Heterocyclic Chem., 41, 461 (2004).Enaminoketones. Introduction.The term enaminone was introduced by Greenhill to define the enamine of a 1,3-diketone, β-ketoester or similar 1,3-difunctional reagents, and is used to indicate any compound containing the conjugated system N-C=C-C=O [1]. Enaminones are versatile synthetic intermediates that combine the ambident nucleophilicity of enamines with the ambident eletrophilicity of enones. The chemistry of the enaminocarbonyl group 1 is potentially an area of considerable scope when one considers that there are present in this moiety, three nucleophilic sites (a, c and e) and two electrophilic sites (b and d) [2][3][4] (Figure 1).Theorically, primary and secondary acyclic enaminones can exist in three tautomeric forms: ketamino form, iminoenol form and oxoimino form [1][2][3]. There is also evidence that cyclic enaminones exist primarily in the enaminoketo form. A study of cyclic enaminoketones shows that these compounds have a significant steric fator in the six-membered ring. The six-membered ring enaminoketones are only slightly stronger bases than the saturated amines, whereas five-and-seven membered rings are much stronger bases than saturated amines. This has been attributed to a large steric strain present in six-membered enaminoketones [5].β-Aminoenones or enaminoketones can exist in four conformations owing to restricted rotations around the C=C double and C-C=O single bonds [3]. Enaminones with primary or secondary amino groups can exist in both Z-and E-forms. If there is a...

Synthesis, reactions and antitumor activity of new β-aminovinyl 3-pyrazolyl ketones

“…[1][2][3][4][5][6][7][8][9][10] Furthermore, it is well known that the β-enaminones of the general formula R 2 N-CH=CH-COR' combine the ambident nucleophilicity of enamines with the ambident electrophilicity of enones. 11,12 Because of this, they have been utilized as versatile valuable precursors for heterocyclic synthesis. 13,14 Their synthetic applications have been extensively reviewed.…”

“…13,14 Their synthetic applications have been extensively reviewed. 12,[15][16][17][18][19][20][21][22][23][24][25][26][27] Furthermore, many enaminones were found to exhibit several biological activities as antitumor, antibacterial and anticonvulsant agents. 28,29 In the light of these facts, it was thought interesting to synthesize a new series of β-dimethylaminovinyl 3-pyrazolyl ketones 4 which are novel enaminones that have been unreported hitherto and study their 1,3-dipolar cycloaddition to the nitrilimines, generated in situ by base-catalyzed dehydrohalogenation of hydrazonoyl halides R-C(X)=NNH-Ar 2.…”

Reactions of nitrilimines with heterocyclic amines and enamines. Convenient methodology for synthesis and annulation of heterocycles

“…Several review articles covering their chemistry have appeared in literature. [10][11][12][13][14][15][16][17] A survey of these reviews together with those dealing with the chemistry of nitrilimines and their hydrazonoyl halides precursors reveals that little focus, if any, has been made hitherto on reactions of nitrilimines with enamines and heterocyclic amines. Our intention in this review is to remedy this situation through presenting the highlights of such reactions that have been reported from our laboratory and from others within the period from 1985 to mid 2006 and contained in Chemical Abstracts.…”

Regioselective acylation of β-enaminones of homoveratrylamine

“…1,2 Their synthetic applications have been extensively reviewed. 3,4 Functionalized 1,2,3,4-tetrahydro-β-carbolines 5 and 1,2,3,4-tetrahydroisoquinolines 6,7 can be synthesized via the Pictet-Spengler reaction starting from β-enaminones containing (hetero)arylethyl substituents tethered to the nitrogen. Some β-enaminones are pharmacologically active in their own right and exhibit anticonvulsant activity.…”