Acid-catalyzed ring-opening reactions of a cyclopropanated 3-aza-2-oxabicyclo[2.2.1]hept-5-ene with alcohols.

Katrina Tait,Alysia Horvath,William Tam,Nicolas Blanchard

doi:10.3762/bjoc.13.281

Abstract

The acid-catalyzed ring-opening reactions of a cyclopropanated 3-aza-2-oxabicylic alkene using alcohol nucleophiles were investigated. Although this acid-catalyzed ring-opening reaction did not cleave the cyclopropane unit as planned, this represent the first examples of ring-openings of cyclopropanated 3-aza-2-oxabicyclo[2.2.1]alkenes that lead to the cleavage of the C–O bond instead of the N–O bond. Different acid catalysts were tested and it was found that pyridinium toluenesulfonate in methanol gave the best yields in the ring-opening reactions. The scope of the reaction was successfully expanded to include primary, secondary, and tertiary alcohol nucleophiles. Through X-ray crystallography, the stereochemistry of the product was determined which confirmed an SN2-like mechanism to form the ring-opened product.

Highlights

Heterobicyclic alkenes are useful templates to generate complex cyclic and acyclic systems [1,2]. 3-Aza-2-oxabicyclic alkenes are interesting due to their asymmetric nature and the ability to modify selected components of the molecule to create vastly different products. 3-Aza-2-oxabicyclic alkenes are generally modified in one of four ways (Scheme 1)
We aim to explore the use of an acid catalyst with an alcohol nucleophile on the ring-opening of cyclopropanated 3-aza-2-oxabicyclic compound 19 for the cleavage of the C–O bond (b) (Scheme 4)
The use of p-toluenesulfonic acid monohydrate produced the ring-opened product at a yield of 38% (Table 1, entry 7) while using camphorsulfonic acid (CSA) increased the yield to 50% but took 46 hours to go to completion (Table 1, entry 8)

Summary

Introduction

Heterobicyclic alkenes are useful templates to generate complex cyclic and acyclic systems [1,2]. 3-Aza-2-oxabicyclic alkenes are interesting due to their asymmetric nature and the ability to modify selected components of the molecule to create vastly different products. 3-Aza-2-oxabicyclic alkenes are generally modified in one of four ways (Scheme 1). 3-Aza-2-oxabicyclic alkenes are interesting due to their asymmetric nature and the ability to modify selected components of the molecule to create vastly different products. 3-Aza-2-oxabicyclic alkenes are generally modified in one of four ways (Scheme 1). One of the most interesting manipulations of 3-aza2-oxabicyclic alkenes is the modification of the alkene component. The manipulation of the olefin can lead to a wide variety of products often in a single step, which is synthetically useful to create many highly substituted products with different stereochemical outcomes (Scheme 2). There are many reported examples in the literature of the modification of the alkene component which includes the reduction to form alkane 8 [3], oxidative cleavage of the C=C bond to form 9 [4], ring-opening metathesis to form functionalized alkenes and [4], dihydroxylation to form diol [5], ruthenium-catalyzed [2 + 2] cycloaddition with unsymmetrical alkynes to form regioisomers. Scheme 1: General reaction pathways for 3-aza-2-oxabicyclic alkenes

Objectives

Results

Conclusion