Simple Reagents for Direct Halonium-Induced Polyene Cyclizations

Abstract

Although there are many reagent combinations that can initiate polyene cyclizations, simple electrophilic halogen sources have not yet proven broadly effective as promoters of such processes. Herein is described a readily prepared and stable class of reagents capable of effecting such transformations for a wide range of electron-rich and -deficient terpenes derived from geraniol, farnesol, and nerol, thereby enabling the effective synthesis of a diverse array of complex chlorine-, bromine-, and iodine-containing polycyclic frameworks. Efforts to date have led to the first racemic laboratory total synthesis and structural revision of the anti-HIV natural product peyssonol A as well as an efficient and concise inaugural total synthesis of peyssonoic acid A. They have also permitted formal racemic total syntheses of aplysin-20, loliolide, K-76, and stemodin to be achieved through routes that are typically shorter, higher-yielding, and more environmentally conscious than previous efforts. Preliminary attempts to use chiral forms of the reagent class for enantioselective alkene halogenation are also described.

Recent progress in the synthesis of oxepanes and medium ring ethers

“…18 Employing the recently introduced brominating agent bromodiethylsulfonium bromopentachloroantimonate (BDSB, 36), 19 …”

Current Methods for Asymmetric Halogenation of Olefins

“…[32] Initial explorations into asymmetric variants illustrated that C 2 -symmetrical sulfide derivatives can induce enantioselectivity in the chlorination of olefin 44 (up to 14 % ee) (Scheme 12).…”

4.07 Electrophilic Cyclization

“…115b Snyder and coworkers developed simple reagents such as 432, for direct halonium-induced polyene cyclizations. 122 Electronrich and -deficient terpenes derived from geraniol, farnesol, and nerol could be used for the synthesis of a diverse array of complexes with chlorine-, bromine-, and iodine-containing polycyclic frameworks. Total synthesis of many natural products are achieved with this protocol, such as peyssonol A, peyssonoic acid A (Scheme 116), and formal racemic total syntheses of aplysin-20, loliolide, and K-76.…”