Synthesis of Bridged Oxabicycles via Cascade Reactions involving O-Acyloxocarbenium Ion Intermediates

Abstract

Compared to related electrophilic species, O-acyloxocarbenium ions (AOIs) have been much less utilized in organic synthesis due to the lack of an efficient formation method. Here, we present a facile and simple approach for the generation of AOI from ester and acetal groups. Based on our AOI system with a pendant nucleophile, we obtained a unique bridged bicyclic system via an epoxonium-like transition state. The proposed mechanism is based on experimental and computational studies.

Recent asymmetric synthesis of natural products bearing an α-tertiary amine moiety via temporary chirality induction strategies

“…The intramolecular Friedel–Crafts reaction of 178 via an uncommon O -acyloxocarbenium intermediate 179 led to the formation of compound 180 (Scheme 22). 87 This reaction enabled remote chirality control at the C11 position in a stereospecific manner owing to the (5 R )-stereochemistry of the [2,3]-adduct 178 . Oxidation of 180 afforded the lactam compound 181 , which was subsequently subjected to ozonolysis to yield 182 .…”

Discovery of a Formal Dyotropic Rearrangement during Acid-Mediated Dioxabicyclo[4.2.1]nonanone Formation

“…T he acid-mediated construction of dioxabicyclo[4.2.1]nonanones from acyclic precursors (Scheme 1) was reported recently by Kim and co-workers. 1 For example, compound 1, with a tert-butoxy carbonyl and an acetal group, was readily converted into dioxabicyclo[4.2.1]nonanone 3, presumably via the O-acyl hemiacetal 2. The mechanistic proposal put forth in this report consisted of formation of Oacyloxocarbenium ion 4 from 2 via loss of MeOH, 2 followed by formation of 3 via an epoxonium-like transition structure 5.…”

“…We then computed the reaction pathway using SnBr 4 as a Lewis acid, because SnBr 4 was used for some key mechanistic experiments in ref . The energetically favorable cascade reaction pathway resulting from our calculations is shown in Figure .…”

“…The acid-mediated construction of dioxabicyclo[4.2.1]­nonanones from acyclic precursors (Scheme ) was reported recently by Kim and co-workers . For example, compound 1 , with a tert -butoxy carbonyl and an acetal group, was readily converted into dioxabicyclo[4.2.1]­nonanone 3 , presumably via the O -acyl hemiacetal 2 .…”