Atom-Economical Synthesis of 2-Aminoimidazoles via [3+2] Annulation Catalyzed by Titanacarborane Monoamide

Abstract

An atom-economical synthesis of 2-aminoimidazoles catalyzed by a titanacarborane monoamide is reported. Reactions of propargylamines with carbodiimides, in the presence of 5 mol% [σ:η ^¹:η ⁵-(OCH₂)(Me₂NCH₂)C₂B₉H₉]Ti(NMe₂), afford a new class of substituted 2-aminoimidazoles via [3+2] annulation in good to excellent yields. A possible reaction mechanism is proposed.

catalysis - heterocycles - hydroamination - imidazole - metallacarborane

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<A NAME="RW33210ST-12">12</A>

Some reactions were complete within 18 h, although the reaction of 2a and 3a was finished in 8 h.

<A NAME="RW33210ST-13">13</A>

Typical procedure for a preparative scale reaction of 2 with 3: A 50-mL Schlenk bottle was charged with a toluene solution (20 mL) of catalyst 1 (0.05 mmol), to which was added 2 (1.0 mmol) and 3 (1.0 mmol). The flask was closed in order to prevent the evaporation of amine. The reaction mixture was then heated at 115 ˚C for 18 h. After removal of the solvent, the residue was subject to flash column chromatographic separation on silica gel (230-400 mesh) to give 4.

<A NAME="RW33210ST-14">14</A>

CCDC-803540 contains the supplementary crystallographic data of 4aa for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Center via http://www.ccdc.cam.ac.uk/data_request/cif.

<A NAME="RW33210ST-15">15</A> The conversion of guanidinoalkynes into imidazoles without the assistance of a metal catalyst has been reported, see: Oyler AR. Naldi RE. Stefanick SM. Lloyd JR. Graden DA. Cotter ML. J. Pharm. Sci.  1989,  78:  21