Zn(OTf)₂ promoted rearrangement of 1,2-cyclopropanated sugars with amines: a convenient method for the synthesis of 3-polyhydroxyalkyl-substituted pyrrole derivatives

Abstract

A rearrangement reaction of 1,2-cyclopropanated sugars with alkylamines or arylamines promoted by Zn(OTf ) 2 is described. The method offers a series of 3-polyhydroxyalkyl-substituted pyrrole derivatives with multiple chiral centers in moderate to excellent yields. The epimerization is achieved by inverting the stereochemistry at the free hydroxyl group of the resulting pyrrole, which would give access to many more possible stereoisomers.

Selective Carbon–Carbon Bond Cleavage of Cyclopropanols

“…In 2015, Shao and co-workers demonstrated that amines can act as effective nucleophiles in trapping ring-opened DA cyclopropanes. 438 Interestingly, in contrast to the example with silane-and acyl-based nucleophiles, 437 attack of the amine to the oxocarbenium 1010 is faster than cyclization from the tethered enolate (Scheme 218). In terms of amine substituents, the reaction tolerates various benzyl, alkenyl, propargyl, aryl, and alkyl amines, ultimately allowing for the synthesis of a wide array of substituted pyrroles (1011).…”

“…In 2015, Shao and co-workers demonstrated that amines can act as effective nucleophiles in trapping ring-opened DA cyclopropanes . Interestingly, in contrast to the example with silane- and acyl-based nucleophiles, attack of the amine to the oxocarbenium 1010 is faster than cyclization from the tethered enolate (Scheme ).…”

Recent Advancements in Pyrrole Synthesis

“…Sugars have been shown to serve as viable substrates for pyrrole synthesis. 145 As exemplified in Scheme 33, Koo subjected D-glucose and L-rhamnose to various primary amines in presence of oxalic acid and DMSO. 146 This unique transformation begins with N-glycosylation of the amine, followed by tautomerization to enamine 293; dehydration, tautomerization, and a second imine formation gives intermediate 294, which undergoes a cyclization and dehydration sequence to furnish pyrrole-2-carbaldehyde 292.…”

Recent Advances on Pyrrole Synthesis through Different Annulation Modes

“…Scheme 21 Au-catalyzed rearrangement/cyclization cascade Scheme 22 One pot sequence between 2-furylcarbinols and anilines for pyrrole construction Shao and co-workers [46] reported a Zn(OTf) 2 -catalyzed synthesis of 3-polyhydroxyalkyl-substituted pyrrole derivatives via the coupling reaction between 1,2-cyclopropanated sugars and amines in 2015 (Scheme 23). The corresponding 1,4-dicarbonyl type of intermediate was generated by a Zinc-catalyzed ring opening of cyclopropane moiety.…”