Alexander M. Agafoncev, Tatyana A. Shumilova and Alexey V. Tkachev* Pages 54 - 61 ( 8 )
Background: Trans-epoxide of (+)-3-carene is one of the most easily prepared products of primary functionalization and can be synthesized by oxidation of (+)-3-carene. The trans-epoxide undergoes ring opening reactions when treated with different nucleophilic reagents giving rise to the corresponding vicinal bis-heteroatomic derivatives which are considered as promising chiral reagents. The ring opening with heterocyclic amines is of special interest because the resulting amino alcohols are perspective chiral ligands for asymmetric organic synthesis and are used as chiral auxiliary in the preparation of promising drugs. The ring opening of the trans-epoxide of (+)-3-carene by aromatic amines does not take place when using traditional approaches.
Methods: Microwave irradiation was studied as a factor providing the required transformations. The experiments were carried out using a monomodal microwave reactor with the temperature control by built-in IR sensor. The reaction products were studied by modern spectroscopic techniques. The results of synthetic experiments were rationalized within the model build up by quantum chemical calculations (DFT).
Results: Reaction of trans-epoxide of (+)-3-carene with sodium salts of heterocyclic amines under microwave irradiation in methanol at 120°C for 1 h resulted in epoxide ring cleavage to produce the corresponding 4-substituted 1S,4S,3S,6R-caran-3-ols in good isolated yields (60-83%). The reaction takes place only in the case of sterically unhindered heterocyclic amines (imidazole, pyrazole, 1H-1,2,3- triazole, 4-(4-bromophenyl)-1H-imidazole, benzotriazole, benzimidazole). Bulky heterocyclic amines do not cause substitution reaction but induce decomposition of the starting epoxide. Alkylation of benzotriazole with trans-epoxide of (+)-3-carene proceeds regioselectively, whereas alkylation of benzotriazole with 1,2-epoxycyclohexane affords both regioisomers.
Conclusion: Microwave irradiation of mixtures containing trans-epoxide of (+)-3-carene and sodium salts of sterically unhindered heterocyclic amines induces regio- and stereoselective SN2 epoxide ring cleavage to produce the corresponding chiral 4-substituted 1S,4S,3S,6R-caran-3-ols which belong to novel group of prospective chiral reagents.
(+)-3-carene, (1S, 3S, 4R, 6R)-3, 4-epoxycarane, epoxide ring cleavage, heterocyclic amines, benzotriazole.
Department of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, Department of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk, Department of Natural Sciences, Novosibirsk State University, 630090 Novosibirsk