Chromium(0)‐Catalyzed Tandem Cyclization of α,β‐Unsaturated Thioimidates Containing an Enyne Moiety

Abstract

1-Azabicyclo[n.3.0] ring systems have been attracting much attention of organic chemists as a variety of important bioactive molecules contain these azabicyclic skeletons. [1] In contrast to the abundant approaches to the construction of 1azabicyclo[3.3.0]octane and 1-azabicyclo[4.3.0]nonane systems, the construction of the 1-azabicyclo[5.3.0]decane skeleton has not been extensively developed, although this ring system constitutes the basic core skeleton of the stemona alkaloids, some of which showed promising insecticide and antitussive activities. [2] The central 1-azabicyclo[5.3.0]decane nucleus was formed by 7-membered-ring formation of pyrrolidine derivatives or 5-membered-ring formation of azepine derivatives in most of the previous synthetic strategies, [3] and there were only a few reports [4] on the one-step, stereoselective synthesis of these compounds by tandem cyclization of acyclic precursors (Scheme 1).We have become interested in developing a new method for the stereoselective construction of the 1-azabicyclo-[5.3.0]decane skeleton by using tandem cyclization of easily available compounds. Our basic strategy is shown at the bottom of Scheme 1. By treatment of a,b-unsaturated thio-imidates [5] containing an enyne moiety 1 with an electrophilic transition-metal catalyst, zwitterionic complexes would be generated by 5-endo nucleophilic addition of the nitrogen atom to the electrophilically activated alkyne, [6] followed by ring closure to give 1-azabicyclo[5.3.0]decane derivatives 2, the core skeleton of stemona alkaloids. Herein we describe successful realization of this type of reaction.We first examined the reaction of a,b-unsaturated thioimidate 1 a containing an enyne moiety [7] with [W(CO) 6 ] (10 mol %) under photoirradiation (250 W super high-pressure Hg lamp; Table 1, entry 1). The reaction proceeded as expected, and 1-azabicyclo[5.3.0]decane product, pyrrole 2 a, was obtained in 54 % yield after double-bond migration. We further examined various electrophilic transition-metal catalysts to carry out the reaction more efficiently. AuCl, AuCl 3 , [PtCl 2 (C 2 H 4 )], and [ReCl(CO) 5 ] also showed moderate catalytic activity for this transformation (Table 1, entries 2, 3, 5, 6), but a cationic gold(I) complex, which was widely used as a powerful catalyst for the electrophilic activation of alkynes, [8] failed to promote this reaction (entry 4). Among the group VI metal catalysts, [Cr(CO) 6 ] was found to show the highest activity (Table 1, entries 7, 8), and use of THF as solvent gave the best result (entry 9). Further reduction of the catalyst loading to 5 mol % lowered the yield of the product considerably (Table 1, entry 10).As the deactivation of the catalyst was thought to be due to the coordination of the metal to the sulfur atom of 1 a and/ or 2 a, [9] we then expected that the use of thioimidates containing a bulky substituent on the sulfur atom would Scheme 1. Synthetic strategies toward the 1-azabicyclo[5.3.0]decane skeleton.