Total Synthesis of (±)-Gracilioether F

Abstract

Total synthesis of (±)-gracilioether F was achieved via a pivotal reductive cleavage of 1,2-dioxane from allenic ester in 11 steps. The key 1,2-dioxane species, derived from singlet oxygen and a diene, could be used as a common precursor for a stereocontrolled formation of the crucial 1,4-diol through a reductive cleavage.

Efficient Synthetic Routes to (±)‐Hippolachnin A, (±)‐Gracilioethers E and F and the Alleged Structure of (±)‐Gracilioether I

“…More interestingly, when we tried to convert the C‐1 CH 2 in 30 into a lactone carbonyl group (to obtain 6 ) with RuO 2 /NaIO 4 , an oxidative cleavage occurred at the C‐8—a lactone carbonyl group was installed on the C‐8 rather than C‐1. Although this otherwise impossible transformation made 6 inaccessible through 30 , the resulting 31 could be oxidized at the C‐1 with CrO 3 /Ac 2 O/AcOH as reported by Carreira (also Wong) and thus comprised a formal synthesis of gracilioether F ( 5 ).…”

“…Carreira also completed the first synthesis of (±)‐glacilioether E ( 8 , along with gracilioether F 5 ) later in the same year. Another synthesis of (±)‐glacilioether F by Wong and (±)‐hippolachnin A by Wood and Brown appeared in early 2016. As for gracilioether B (along with gracilioether C, structure not shown in Figure ), it was synthesized for the first time in early 2015 by Perkins, and co‐workers.…”

Progress in the Total Synthesis of Natural Products Embodying Diverse Furofuranone Motifs: A New Millennium Update

“…Bayer-Villiger oxidation of the mixture provided the lactone 220 and a final step involving CrO 3 oxidation of tetrahydrofuran ring in 220 to lactone completed the synthesis of (�)-gracilioether F (203). 's synthesis of (�)-gracilioether F (203) [55] Wong's synthesis of racemic gracilioether F (203) commenced with allenic ester 221 and its Iodine mediated cyclization furnished an iodobutenolide 222 (Scheme 22). [55] γ-Alkylation with 2-bromomethyl-1-butene to 223 and regioselective hydroboration-oxidation of the terminal olefin led to an inseparable mixture of diastereomeric alcohols 224 which upon Dess-Martin oxidation produced a separable mixture of aldehydes 225, 226 respectively; and the undesired isomer 225 could be epimerized to the desired aldehyde 226 with base.…”

Direct Monofluoromethylthiolation with S‐(Fluoromethyl) Benzenesulfonothioate

“…Our group has recently reported several shelf‐stable yet highly reactive electrophilic trifluoromethylthiolating, difluoromethylthiolating–, or ethoxycarbonyldifluoromethylthiolating reagents that are able to react with a broad substrate scope under mild conditions. As an extension of our interests in the development of electrophilic fluoroalkylthiolating reagents, we disclose herein the preparation of S ‐(fluoromethyl) benezenesulfonothioate ( 1 ), a powerful monofluoromethylthiolating reagent that reacts with various aryl boronic acids and olefins under mild conditions to give the corresponding monofluoromethylthiolated compounds in high yields.…”