Synthesis of hexahydro-1H-pyrrolo[1,2-c]imidazole derivatives by sequential azomethine ylide cycloaddition and urea cyclization reactions (original) (raw)
A revised approach to the synthesis of 3-acyl imidazo[1,2-a] pyridines
Heterocyclic Communications, 2010
3-Acyl imidazo[l,2-a]pyridines with no substituent at position 2 were obtained in moderate to good yields in an improved version of the Tisler protocol for the synthesis of imidazo[l,2-x]azines. It was found that yields are significantly improved if the reaction is carried out in the presence of DMF or in some cases in the absence of a solvent. INTRODUCTION The fused heterocyclic system imidazo[l,2-a]pyridine is an important pharmacophore, as is demonstrated by the broad variety of pharmacological activities shown by its derivatives.' The most common approach to the synthesis of the imidazo[l,2-o]pyridine ring is based on the condensation reaction of 2-aminopyridines with a-halocarbonyl compounds. 2 This methodology allows the direct construction of 2 or 2,3-substituted imidazo[l,2-a]pyridines, but is not usefiil for the synthesis of 3-acyl imidazo[l,2-a]pyridines with no substituent at position 2. The interesting aspect of 3-aroyl imidazo[l,2-a]pyridines is their potential biological activity. Thus, derivatives of 2-amino-3-aroyl imidazo [l,2-a]pyridines have been evaluated as antiviral agents. 3 A useful method of synthesis of 3-acyl imidazo[l,2-a]azines is the intramolecular cyclization of alkylated iV-heteroaryl formamidines, described by Tisler. 4,5 Direct thermal regiospecific acylation of 7-methyl imidazo[l,2-a]pyridine has also been reported. 6 Since our research program required 3-aroyl imidazo[l,2-a]pyridines unsubstituted at position 2 to carry out several studies, the Tisler method was the best option to synthesize them. However, in the Tisler protocol the related derivative 2-methyl-3-benzoylimidazo[l,2-a]pyridine 2 was obtained in only 16% yield via condensation of formamidine 1, with the corresponding α-bromoketone. The results of an adaptation of such methodology to the synthesis of 3-acyl imidazo[l,2-a]pyridines unsubstituted at position 2 are presented herein. RESULTS AND DISCUSSION The study began with a multicomponent approach to the 3-acyl imidazo[l ,2-a]pyridine heterocyclic system, employing 2-aminopyridine, 2-bromoacetophenone and formaldehyde. However, from this experiment only 2-phenylimidazo[l,2.a]pyridine was obtained. Then DMFDMA, a well known one carbon synthon useful in the synthesis of heterocycles, 7 was used in place of formaldehyde. This attempt was also unsuccessful, giving only traces of 3-(4'-chlorobenzoyl imidazo[l,2-a]pyridine. Therefore, it was decided to directly treat the jV'-pyridylformamidine 3
Azomethine Ylides—Versatile Synthons for Pyrrolidinyl-Heterocyclic Compounds
Molecules
Azomethine ylides are nitrogen-based three-atom components commonly used in [3+2]-cycloaddition reactions with various unsaturated 2π-electron components. These reactions are highly regio- and stereoselective and have attracted the attention of organic chemists with respect to the construction of diverse heterocycles potentially bearing four new contiguous stereogenic centers. This review article complies the most important [3+2]-cycloaddition reactions of azomethine ylides with various olefinic, unsaturated 2π-electron components (acyclic, alicyclic, heterocyclic, and exocyclic ones) reported over the past two decades.
Tetrahedron, 2006
The 1,3-dipolar cycloaddition of dimethyl acetylenedicarboxylate with nonstabilized azomethine ylides, generated via the decarboxylative condensation of 1,3-thiazolidine-4-carboxylic acids with aldehydes, afforded 5,7a-dihydro-1H,3H-pyrrolo[1,2-c]thiazole derivatives. 2-Substituted-1,3-thiazolidine-4-carboxylic acids led to the stereoselective formation of 5,7a-dihydro-1H,3H-pyrrolo[1,2-c]thiazoles. Quantum-chemistry calculations were carried out allowing the rationalization of the observed stereoselective formation of the anti-dipole.
Heteroatom Chemistry, 1997
Hydrazonoyl bromides 1a-c react with 5-amino-3phenyl-1H-pyrazole, 5-amino-1H-1,2,4-triazole, 2aminopyridine, 2-aminopyrimidine, and 2-aminobenzimidazole to afford the corresponding imidazo[1,2-b]pyrazoles 10, imidazo[1,2-b]-1,2,4-triazoles 11, imidazo[1,2-a]pyridines 16, imidazo[1,2-a]pyrimidines 17, and imidazo[1,2a]benzimidazoles 20, respectively. Compounds 1a-c reacted also with 2-methylthiobenzimidazole to give 1,2,4-triazolo[4,3-a]benzimidazole derivatives 21.
Tetrahedron Letters, 2009
The synthesis of the tetracyclic core of nakadomarin A is described. The core contains all the heterocycles and the required stereocenters found in the natural product and provides a promising route to the target itself. The strategy utilizes a general, diastereoselective pyrrolidine synthesis that proceeds via a homo 3 + 2 dipolar cycloaddition. The scope of this methodology is also described.
The synthesis of 1,2,3,6,6a,7-hexahydro-7-methyl-5-imino-1H-pyrrolo[1,2-c]imidazolo[5,4-b]indole
Arkivoc, 2009
This paper is dedicated to Henk van der Plas who has for many years inspired heterocyclic chemists the world over with his innovative research, his impeccable standards and his charming personality Abstract N-3-(1-Methylindol-3-yl)propan-N-(2,2,2-trichloroethoxysulfonyl)guanidine was synthesized from 3-formyl-1-methylindole in six steps and subjected to conditions intended to convert the side-chain into a 2-iminotetrahydropyrimidine-containing product, of relevance to a possible synthesis of the aplicyanins. An alternative reaction course was observed, resulting in the formation of a new tetracyclic system.