Rapid and Stereocontrolled Synthesis of Racemic and Optically Pure Highly Functionalized Pyrrolizidine Systems via Rearrangement of 1,3-Dipolar Cycloadducts Derived from 2-Azetidinone-Tethered Azomethine Ylides

This work describes a convenient procedure for the straightforward preparation of polyfunctionalized enantiopure pyrrolizidine systems. The methodology capitalizes on a HCl(g)-promoted reaction of the 1,3-dipolar cycloadducts derived from 2-azetidinone-tethered azomethine ylides, smoothly affording different types of highly functionalized bi- and tricyclic systems in racemic and optically pure forms. This process involves a selective bond cleavage of the four-membered ring, followed by a rearrangement under the reaction conditions. The synthetic route employed was shown to be compatible with a variety of 4-oxoazetidine-2-carbaldehydes, alpha-amino esters, or dipolarophiles, offering a versatile entry to pyrrolizidine systems.