Synthesis of Imidazo[1,2-a]pyridines via Near UV Light-Induced Cyclization of Azirinylpyridinium Salts

Abstract

An efficient one-pot synthesis of imidazo[1,2a]pyridines from 2-bromoazirines and pyridines has been developed. The construction of the bicyclic framework of imidazo[1,2-a]pyridines occurs in two steps through the formation of (2H-azirin-2-yl)pyridinium bromides followed by dehydrobrominative UV light-induced cyclization. The method can also be applied for the synthesis of imidazo[2,1-a]isoquinolines. Unstable in solution, (2H-azirin-2-yl)pyridinium/isoquinolinium bromides were quantitatively converted to stable tetrafluoroborates, which can be cyclized to imidazo[1,2-a]pyridines under UV irradiation in the presence of bromide ions.2H-Azirines due to their diverse reactivity are widely used in the synthesis of various nitrogen heterocycles. 1 A number of effective methods have been developed to selectively transform the azirine ring into other N-heterocycles, such as dihydroazetes, pyrroles, and pyridines, as well as various N,N-and N,O-heterocycles, such as isoxazoles, oxazoles, pyrazoles, oxazines, pyrazines, and pyrimidines. Azirines are also convenient starting materials for the synthesis of various (3,5)-, (3,6)-, (5,6)-, and (6,6)-bicyclic systems, in which they are embedded as the N−CC, NC−C, or CC structural fragments. The annulations of cyclic molecules with azirines have been successfully applied to the preparation of both nonaromatic and aromatic fused heterocycles, the latter being represented in the literature by incomparably fewer examples. Among them, the methods for the preparation of indoles 2 and their benzo-fused derivatives, 3 benzofurans, 4 and 5H-pyrazino-[2,3-b]indoles 5 are most thoroughly developed. One of the efficient approaches to the synthesis of indoles is a catalytic isomerization of 2-arylazirines. It can also be applied to the preparation of azaindoles (diazaindenes) of pyrazolo[1,5a]pyridine and 1H-pyrrolo[2,3-c]pyridine series using 2-(pyridin-2-yl)-6 or 2-(pyridin-4-yl)azirines 7 as starting compounds (Scheme 1, reaction 1). A significant disadvantage of this method is the limited availability of the starting pyridylazirines because they have to be synthesized from nontrivial pyridine-containing precursors. Azirines with a cationic pyridinium substituent, azirinylpyridinium salts, are completely unknown. At the same time, these compounds could be of interest as potential precursors of such an important class of azaindoles as imidazo[1,2-a]pyridines. The imidazo[1,2-a]pyridine derivatives display anticancer, 8 antiviral, 9 anticonvulsant, 10 antimycobacterial, 11 and antileishmanial 12 activity. They also have attracted a great deal of attention

Stable 2-Azaallyl Salts as a Bridge between 2H-Azirines and Densely Functionalized 2H-Pyrroles

“…The highest yield of 77% was achieved when iodoazirine 1a I was used as a starting compound. Azirinylpyridinium salt 1a Py also can be used as the starting material for the preparation of compound 2a but the efficiency of its reaction in comparison with the reactions of the iodoazirine and even bromoazirine is lower.…”

HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

“…Some recent synthetic approaches to imidazo[1,2- a ]pyridine scaffolds include synthetic pathways of transition metal-catalyzed reactions [ 14 ], cyclization [ 15 ], condensation [ 16 ], heteroannular [ 17 ], and photocatalytic reactions [ 18 ]. These approaches usually involve non-trivial reaction conditions and the employment of relatively complex starting materials [ 19 ].…”

Late‐stage functionalization of Vouacapane derivatives from Caesalpinia platyloba by a Groebke−Blackburn−Bienaymé reaction

“…[10][11][12] Nevertheless, other works that do not involve the use of isocyanides have been described. [13][14][15] In this context, only two research groups have used natural-product derivatives as starting reagents in GBB reactions. In 2012, Krasavin and Sandulenko used a derivate of anabasine 2 as amino component toward 6-(piperidin-2-yl)imidazo [1,2-a]pyridines in moderate yields (Scheme 1A).…”

“…for C 23 H 29 O 4 [M + H] + : 369.2066; Found: 369.2058. General procedure for (4AS,5R,11 BS)-9-(3-(tert-butylamino)imidazo[1,2-a] pyridin-2-yl)-4,4,7,11b-tetramethyl-1,2,3,4,4a ,5,6,11b-octahydrophenanthro[3,2-b]furan-5-yl acetate(14)…”