Variants of the Prins Cyclization for the Synthesis of Terpenoid Spiroethers and Oxabicyclo[3.3.1]Nonane Derivatives

Abstract

Terpenoid spiroethers are abundant natural flavors with significant impact, particularly in the food industry. We present in this article the synthesis of new derivatives of the well-known flavors theaspirane and vitispirane using a variant of the Prins cyclization starting from α,β-unsaturated or heterocyclic ketones. When aromatic ketones were used as the starting materials for Lewis acid-mediated cyclizations, an alternative pathway involving a domino sequence of Prins cyclization, followed by an intramolecular Friedel-Crafts alkylation, gave benzoannelated oxabicyclo[3.3.1]nonane derivatives. Different reaction pathways may be triggered by the reaction temperature to give with good selectivity either tetrahydropyran derivatives as conventional Prins products or oxabicyclo[3.3.1]nonane derivatives.

A Domino Aza-Prins/Friedel–Crafts Reaction for the Synthesis of Benzomorphans

“…8c-l,10 We have recently reported a sequence of Prins cyclization and intramolecular Friedel-Crafts reaction with aryl acetones 1 and isoprenol derivatives 2 (Scheme 1). 11 The first step of this sequence is a silyl-modified Sakurai-type reaction that was developed by Marko for the synthesis of dihydropyrans. 12 A subsequent Friedel-Crafts conversion gives benzoannelated oxabicyclo [3.3.1]nonanes 3 that cannot easily be prepared by other methods.…”

“…This parallels our observations in recent Prins/Friedel-Crafts conversions into oxabicyclononanes 3. 11 The scope of the reaction is quite general and a number of different aromatic aldehydes and homoallylamines can be converted into the corresponding benzomorphans 6. A summary of the products is presented in Scheme 3 along with the X-ray crystal structure of 6c as a representative…”