A Formal Total Synthesis of (+)‐Frondosin A

Abstract

An enantio‐ and stereoselective formal total synthesis of (+)‐frondosin A was accomplished through an oxidopyrylium‐ion‐mediated [5+2] cycloaddition reaction. The cycloaddition reaction provided not only an efficient way of constructing the frondosin skeleton but also facial discrimination through an ether bridge for complete control of relative stereochemistry of the substituents in frondosin A.

Sulfonyl Hydrazides in Organic Synthesis: A Review of Recent Studies

“…They were successfully used for the total synthesis of natural products, which included Brasilicardins A and C, (+)‐Frondosin A, (+)‐Tanikolide, Lundurines A−C, Onoseriolid, Isobolivianine, (−)‐Crinipellin A, Panaginsene, Echinopines, (+)‐ and (−)‐Isolaurepan, (−)‐Strychnofoline, (−)‐Clovan‐2,9‐dione, (+)‐Sarcophytin, [2 ° ] (+)‐Chatancin, [2 ° ] (−)‐3‐Oxochatancin, [2 ° ] (+)‐Cyperolone . In these cases, TsNHNH 2 reacted with aldehydes (or ketones) to form hydrazones that underwent cycloaddition or reduction subsequently. Banford‐Stevens reaction and Shapiro reaction were reported in this decade.…”

Oxidopyrylium [5+2] cycloaddition chemistry: Historical perspective and recent advances (2008–2018)

“…97 The class of molecules has also been of high interest to the synthetic organic chemistry community, and have served as targets in multiple total syntheses. 98 Recently, Lee and coworkers used oxidopyrylium cycloaddition to complete the 7-membered ring of frondosin A (Scheme 52), 99 intercepting an intermediate used by Trost ( 52.5 ) in his own synthesis. 100 The Lee group is able to use the oxidopyrylium cycloaddition to relay the stereochemistry from a nearby benzyl ether to set the correct stereochemistry of the natural products aryl appendage ( 52.4 ).…”

Furan Oxidation Reactions in the Total Synthesis of Natural Products

“…Furfuryl alcohol 380, obtained by condensation of 3-methyl-2-(siloxymethyl)furan 379 with the corresponding aldehyde, was treated with TBHP/VO(acac) 2 followed by acylation of the formed hemiacetal in order to produce pyranone derivative 381. This pyranone was cyclized to give compound 382 (Scheme 93), 143 which earlier was transformed into (+)-frondosin A (383) by a straightforward three-step sequence. 144 Tong and Li reported the total synthesis of (-)-hedycoropyrans A and B using KBr/Oxone for the oxidation of 3aryl-1-furylpropane-1,2-diol 384, which was synthesized from furfural (31) in a straightforward manner.…”