Arylation of Cyclopropanol with Pyrrole: Asymmetric Synthesis of Indolizidine 167B, Indolizidine 209D, and Monomorine I

Abstract

A Fe(NO 3 ) 3 -mediated ring-opening arylation of cyclopropanol with the electron-rich pyrrole has been developed, which might proceed through oxidative radical ring opening of cyclopropanol followed by cyclization to the pyrrole motif and then aromatization. This method enables direct arylation of cyclopropanol without prefunctionalization and thus allows rapid access to a diverse array of chiral 5,6,7,8-tetrahydroindolizines from easily available chiral amino acid esters. The synthetic utility has been demonstrated by the asymmetric synthesis of alklaoids (−)-indolizidine 167B, (+)-indolizidine 209D, (+)-monomorine I, and a natural product analogue.

Ring‐Opening Cross‐Coupling/Cyclization Reaction of Cyclopropanols with Organic Compounds

“…). [80] In this procedure, cyclopropanol derivatives 121 that derived from amino acid esters 120, underwent iron(III) catalyzed radical ring-opening and intramolecular annulation with electron-rich pyrroles. This synthetic method was successfully applied for the preparation of bioactive molecules, like (À )-indolizidine 167B, (+)-indolizidine 209D, (+)-monomorine I.…”

“…At the same time, another work in ring‐opening/cyclization of cyclopropanols and pyrroles was accomplished to yield a broad range of indolizine derivatives 122 (Scheme 69). [80] In this procedure, cyclopropanol derivatives 121 that derived from amino acid esters 120 , underwent iron(III) catalyzed radical ring‐opening and intramolecular annulation with electron‐rich pyrroles. This synthetic method was successfully applied for the preparation of bioactive molecules, like (−)‐indolizidine 167B, (+)‐indolizidine 209D, (+)‐monomorine I.…”

Gold(I)-Catalyzed Functionalization of Pyrrole Derivatives: Stereoselective Synthesis of 7,8-Disubstituted 7,8-Dihydroindolizin-6(5H)-ones

“…9 A Fe(NO 3 ) 3mediated ring-opening arylation of cyclopropanol with an electron-rich pyrrole was recently applied to the synthesis of functionalized alcohols (Scheme 1, eq 2). 10 We recently described a gold-catalyzed domino cycloisomerization/alkoxylation of indole skeletons leading to 3,4-dihydro-1H-[1,4]oxazino[4,3-a]indole 11 and observed a domino process of naphthalene derivatives that combined a C−O rearrangement in the presence of Lewis acid. 12 The importance of access to diverse pyrrole derivatives led us to examine the preparation of 7,8-dihydroindolizin-6(5H)-ones, as a key platform for the synthesis of bioactive compounds (Scheme 1, eq 3).…”

“…Additionally, they have optical properties as fluorophores . Consequently, this family of molecules represents an outstanding target for the development of new and efficient synthetic routes, as showcased in multiple publications . Of particular note are approaches directed toward the synthesis of naturally occurring indolizine alkaloids, including (−)-curvulamine and related structures …”

“…Newer methods have recently emerged, utilizing pyrrole units in processes such as annulation, C–H functionalization, or ring-opening reactions . A Fe(NO 3 ) 3 -mediated ring-opening arylation of cyclopropanol with an electron-rich pyrrole was recently applied to the synthesis of functionalized alcohols (Scheme , eq 2) . We recently described a gold-catalyzed domino cycloisomerization/alkoxylation of indole skeletons leading to 3,4-dihydro-1 H -[1,4]oxazino[4,3- a ]indole and observed a domino process of naphthalene derivatives that combined a C–O rearrangement in the presence of Lewis acid .…”