Enantioselective Pd‐Catalyzed Allylic Alkylation Reactions of Dihydropyrido[1,2‐a]indolone Substrates: Efficient Syntheses of (−)‐Goniomitine, (+)‐Aspidospermidine, and (−)‐Quebrachamine

Abstract

The successful application of dihydropyrido[1,2-a]indolone (DHPI) substrates in Pd-catalyzed asymmetric allylic alkylation chemistry facilitates rapid access to multiple alkaloid frameworks in an enantioselective fashion. Strategic bromination at the indole C3 position greatly improved the allylic alkylation chemistry and enabled a highly efficient Negishi cross-coupling downstream. The first catalytic enantioselective total synthesis of (−)-goniomitine, along with divergent formal syntheses of (+)-aspidospermidine and (−)-quebrachamine are reported herein.

Catalytic Enantioselective and Diastereoselective Allylic Alkylation with Fluoroenolates: Efficient Access to C3‐Fluorinated and All‐Carbon Quaternary Oxindoles

“…[8] In this regard, Trost's asymmetric allylic alkylation (AAA) would be a preferable reaction due to its outstanding value in natural product synthesis. [9] Although many examples of allylic alkylations producing a single chiral center with high asymmetric induction are known, the stereocontrolled formation of two adjacent chirality centers continues to be a challenge. [10] …”

Scalable Enantioselective Total Synthesis of (−)‐Goniomitine

“…Recently, Stoltz et al. employed a palladium‐catalyzed asymmetric allylic alkylation reaction as a key step to install the chiral alkylated quaternary stereocenter in the enantioselective synthesis of 1 ,. Here we report a scalable enantioselective synthesis of (−)‐goniomitine ( 1 ) based on an iridium‐catalyzed asymmetric hydrogenation of racemic 5‐membered exocyclic enone esters.…”

Stereocontrolled Synthesis of Melokhanine E via an Intramolecular Formal [3+2] Cycloaddition

“…9 One of the most successful and broadly used strategies was developed by the Stoltz group which employs racemic 3,3-disubstituted piperidines and chiral palladium catalysis to obtain enantioenriched 3,3disubstituted piperidines with good yields and up to 99% enantiomeric excess. [10][11][12] While high-yielding and stereoselective, these approaches yield products at non-ideal oxidation states for their direct advancement to the target natural products. The approach to the piperidine scaffold presented herein is inspired by Waser and co-workers' efforts on push-pull cyclopropane opening and subsequent cycloadditions, allowing for direct access to piperidines at the desired oxidation states.…”