The Mukaiyama type aldol reaction for the synthesis of trans-2,6-disubstituted tetrahydropyrans: synthesis of diospongin A and B

Abstract

The synthesis of 2,6-trans-disubstituted tetrahydropyrans following the Mukaiyama type aldol reaction through C–C bond formation demonstrates the practicality of this protocol in the total synthesis of diospongin A and B.

Recent Advances in the Synthesis of Diarylheptanoids

“…Reaction of 214 with excess TBAF furnished 76 a via retro-Michael opening of pyran ring followed by an intramolecular oxy-Michael reaction and desilylation leading to a more thermodynamically stable cis isomer (Scheme 57). [129] Dongjoo Lee's research group (2021) reported a dehydrogenative cycloetherification of a hydroxyl alkene through 6endo cyclization, yielding a dihydropyran employing DDQ. This method was effectively applied in the synthesis of racemic (�)centrolobine.…”

“…Reaction of 214 with excess TBAF furnished 76 a via retro‐Michael opening of pyran ring followed by an intramolecular oxy‐Michael reaction and desilylation leading to a more thermodynamically stable cis isomer (Scheme 57). [129] …”

Concise Total Synthesis of Curvulone B

“…Very recently, we reported the synthesis of 2,6-trans-disubstituted tetrahydropyrans with a keto functionality following a Mukaiyama-type aldol reaction of 1-phenyl-1triemthylsiloxyethylene with six membered cyclic hemiacetals in the presence of iodine. 6 To apply further the Mukaiyama-type aldol reaction and as a part of our ongoing research on the total synthesis of biologically active natural products containing pyran rings, 7 herein, we report an efficient and convergent synthesis of curvulone B in seven steps.…”

“…Tandem isomerization followed by a C-O and C-C bond formation protocol under Mukaiyama-type conditions was performed by treating 7 with trimethyl(vinyloxy)silane in the presence of a catalytic amount of molecular iodine in anhydrous CH2Cl2 at room temperature to furnish trans-2,6-disubstituted-3,4-dihydro-pyran 5 as the sole product in 81% yield. 6,9,10 Scheme 2 Synthesis of compound 5…”