Introduction

Highly substituted and stereodefined THF ring systems are prevalent in biologically active molecules such as (+)-Amphidinolide T1 and (+)-Crobarbatic acid.

Previously we have shown that the reaction of 2-alkoxy-dihydropyrans 2 (R≠H) with DMDO gives rise to 2,3-cis THFs with high stereocontrol (Scheme 1).  The process is believed to go via an epoxidation occurring trans to the substituent at C4 followed by ring contraction to selectively yield 2,3-cis-substituted THFs.

However, this DMDO chemistry is unsuccessful for substrates where R=H which would provide products such as 5 with a synthetically versatile aldehyde unit.  Alternative epoxidation systems have therefore been explored.  

Results

Reactions for a range of 2-alkoxy-dihydropyrans with methyltrioxorhenium (MTO) afforded the desired lactol ether 8 in moderate yields (Scheme 2). Subjection of 8 to Jones oxidation gave the desired 4,5-cis tetrahydrofuranones including (±)-Crobarbatic acid.  The scope and limitations of this chemistry are described.