Nickel‐Catalyzed Enantioselective Synthesis of 2,3,4‐Trisubstituted 3‐Pyrrolines

Abstract

The development of synthetic methods to produce highly functionalized chiral 3-pyrrolines is of indisputable importance because of their prevalence in natural and synthetic bioactive molecules. Unfortunately, previous general cycloaddition approaches using allenoates, could not synthesize 3,4-disubstituted 3pyrrolines. Herein, an original approach to yield 2,3,4trisubstituted 3-pyrrolines with chirality at the 2-position is presented. A Ni II /Fc-i-PrPHOX catalytic system facilitated a redox-neutral highly stereoselective process that exhibited an enantioselectivity of up to 99 %. Enantioenriched 3-pyrrolines can be converted to other valuable classes of N-heterocycles.

Construction of a Pentacyclic Framework Enabled by Nickel Catalysis

“…On the basis of the results and previous reports, , the plausible mechanism is proposed (Scheme a). The transmetalation of arylboronic acid 2 to the nickel complex A affords arylnickel species B , which is then subjected to insertion into alkyne 1 .…”

Recent Developments in Enantioselective Domino Reactions. Part B: First Row Metal Catalysts

“…In 2022, Iqbal and Cho described an original novel methodology to synthesize 2,3,4-trisubstituted chiral 3pyrrolines 189 on the basis of an enantioselective nickel-catalyzed domino addition/cyclization reaction of various alkyne-tethered N-sulfonamide acrylates 190 with (hetero)arylboronic acids 191. [58] The reaction employed 10 mol% of Ni(OAc)•4H 2 O as precatalyst and the same quantity of chiral phosphinoferrocenyloxazoline ligand 192. Performed at 80 °C in TFE as solvent, it led to a wide range of highly functionalized chiral 3-pyrrolines 189 with both moderate to excellent yields (40-96%) and enantioselectivities (62-99% ee), as shown in Scheme 48.…”

“…In 2022, Iqbal and Cho described an original novel methodology to synthesize 2,3,4‐trisubstituted chiral 3‐pyrrolines 189 on the basis of an enantioselective nickel‐catalyzed domino addition/cyclization reaction of various alkyne‐tethered N ‐sulfonamide acrylates 190 with (hetero)arylboronic acids 191 [58] . The reaction employed 10 mol% of Ni(OAc)⋅4H 2 O as precatalyst and the same quantity of chiral phosphinoferrocenyloxazoline ligand 192 .…”

Recent Progress in Arylmetalative Cyclization/Annulation of Functionalized Alkynes with Organoboranes

“…anti ‐Arylmetalative cyclization on specifically designed alkynes affords unusual architectures with cyclic endo ‐alkene derivatives [39–55] . In this realm, Tsukamoto group discovered the abnormal trans ‐addition of organoboronic reagents on alkynals and alkynones using palladium(0) catalyst [38] .…”