Stereoselective Synthesis of Donor‐Acceptor Cyclopropapyranone by Intramolecular Cyclopropanation of Vinylogous Carbonates: Application to the Total Synthesis of (±)‐Diospongin B

Abstract

An intramolecular, stereoselective cyclopropanation of vinylogous carbonates with carbenes using copper catalyst is developed for the synthesis of donor‐acceptor substituted cyclopropapyranones. Completely regioselective ring cleavage of each of the cyclopropane bonds was achieved under suitable reaction conditions, leading to a diverse array of cyclic ethers. The developed method is utilized in the total synthesis of (±)‐diospongin B.

Stereodivergent Assembly of 2,6-cis- and -trans-Tetrahydropyrans via Base-Mediated Oxa-Michael Cyclization: The Key Role of the TMEDA Additive

“…Thus, cis - and trans -THPs 4b derived from phenyl-substituted ester 1b were used as precursors to the antiosteoporotic natural compounds Diospongins A ( 6 ) and B ( 7 ) . Reductive ozonolysis of the methylene double bond in trans - 4b afforded the corresponding pyranone 8 , which can be converted into Diospongin B ( 7 ) according to a known method, thus representing the formal synthesis of this natural product. On the contrary, ozonolysis of cis - 4b and subsequent diastereoselective reduction, silylation, conversion of ester to phenyl ketone, and silyl deprotection furnished Diospongin A ( 6 ) (Scheme a).…”

“…R f = 0.69 (PE/EtOAc, 4:1). [α] D 20 = +37 (c 0.70, CHCl 3 ). IR (neat): ν = 1738, 1654, 1437, 1279, 1161, 1095, 996 cm −1 .…”

Recent Advances in the Synthesis of Diarylheptanoids

“…[122] Gharpure research group ( 2016 ). [123] Clarke and collaborators ( 2016 [124] Alejandro and team (2016) reported a free radical ionic sequence followed by intermolecular iodolactonization in the synthesis of tetrahydropyran diarylheptanoid (À )-de-O-methylcentrolobine 205. Enantiomerically enriched allylic alcohol 206 on reaction with iodoacetic acid in presence of radical initiator dilauroyl peroxide (DLP) underwent iodolactonization followed by deiodination resulted in tetrahydropyran lactone 207.…”

Synthetic Approaches to Diospongins: A Two Decade Journey

“…In 2015, the Gharpure group executed the synthesis of (±)-diospongin B using a stereoselective intramolecular cyclopropanation of a vinylogous carbonate with carbene using a copper catalyst as the key step. 37 The approach commenced with selective protection of the primary alcohol of butane-1,3-diol (149), as its TBS ether, followed by addition of the secondary alcohol to ethyl propiolate using N-methyl morpholine (NMM), to provide the vinylogous carbonate 150. Next 150 was converted into acid 151 using Jones' reagent by simultaneous protodesilylation, followed by oxida-tion, in 68% overall yield.…”