Studies On Novel[4+1] Cycloaddition Reactions For The Synthesis Of Tetrahydrofurans

Tetrahydrofurans are a class of fundamentally important heterocycles widely found in numerous biologically important natural products and medicines.For this reason,development of highly efficient and convenient methods for the construction of such heterocycles has been actively pursued by chemists for decades.Enabled by the capability for simultaneous formation of C-C and C-O bonds in a single step,cycloaddition reactions provide an attractive and powerful strategy for highly efficient synthesis of these compounds.Currently,such cycloaddition strategies predominantly rely on the transition metal or Lewis acid-catalyzed [3+2] cyclization processes.As an alternative strategy,[4+1] cyclization approaches,however,have been far less developed.Therefore,development of novel [4+1] cycloaddition reactions for the synthesis of tetrahydrofurans remains highly desirable.In this thesis,we have designed and synthesized a series of peroxides,which function as electrophilic oxygen and carbon reagents,to engage in cascade C-C and C-O bond-forming reactions with one-carbon unit nucleophiles such as 1,3-dicarbonyl compounds,thereby affording a distinct formal [4+1] cycloaddition reaction for the synthesis of functionalized 2,2-disubstituted tetrahydrofurans with high yields under mild conditions.This new method is operationally simple without using any transition metals,and the reaction scope is very general.In addition,unlike traditional approaches mainly relying on the attack of nucleophilic oxygens with electrophilic carbons to form the critical C-O bonds in tetrahydrofuran rings,our method conversely utilized the corresponding carbon nucleophiles and electrophilic oxygen sources to construct such C-O bonds.More importantly,by incorporating efficient chiral auxiliary groups into the nucloephiles,this approach could be flexibly switched to the asymmetric synthesis of chiral tetrahydrofurans in a single step.Upon on screening of several important chiral auxiliaries,we found the chiral mentol-tethered 1,3-dicarbonyl compounds could smoothly undergo the asymmetric cyclizations,affording the chiral tetrahydrofuran products in 55% yield and 2:1 diastereoselectivities.These initial results evidently proved the feasibility of such asymmetric [4+1] cycloaddition strategy and will provide a good starting point for our future research.