Enantioselective Alkylation of 2‐Oxindoles Catalyzed by a Bifunctional Phase‐Transfer Catalyst: Synthesis of (−)‐Debromoflustramine B

Abstract

A new bifunctional phase-transfer catalyst that employs hydrogen bonding as a control element was developed to promote efficient enantioselective S 2 reactions for the construction all-carbon quaternary stereocenters in high yield and excellent enantioselectivity (up to 97 % ee) utilizing the alkylation of a malleable oxindole substrate. The utility of the methodology was demonstrated through a concise and highly enantioselective synthesis of (-)-debromoflustramine B.

Assisted by Hydrogen-Bond Donors: Cinchona Quaternary Salts as Privileged Chiral Catalysts for Phase-Transfer Reactions

“…In 2018, the Connon group 34 developed complex urea derivatives of Cinchona alkaloids C18 additionally modified within the quinoline ring. These catalysts were used in the highly enantioselective alkylation reaction of oxindole derivatives 24 (Scheme 13).…”

Base-free enantioselective SN2 alkylation of 2-oxindoles via bifunctional phase-transfer catalysis

“…However, despite the excellent levels of enantiocontrol often achieved, in the majority of these studies the 2-oxindole subjected to enantioselective alkylation lacks the structural architecture necessary for further modifications ( Scheme 1A ), presenting instead a fixed – not easily modifiable – group which is not ideal for a modular approach to the construction of more complex molecules such as those shown in Figure 1A . Recently, we partially overcame this challenge by developing a highly enantioselective phase-transfer-catalysed methodology for the S N 2 alkylation of methylene ester-substituted 2-oxindole 4 [ 31 ]. The utility of this methodology has been demonstrated through the total synthesis of (−)-debromoflustramine B ( Scheme 1B ).…”

Copper(I)‐Catalyzed Cascade Cyclization to the Total Synthesis of Hexahydropyrroloindole Alkaloids: Flustramine B and Debromoflustramine B

“…Based on its interesting biological activities and the synthetic challenging of tetrasubstituted stereocenters, which has been attracted significantly attention in organic chemistry. For the past decades, many novel synthetic routes have been reported for the construction of these architectures, and to further access hexahydropyrroloindole (HPI) alkaloids, [13][14][15][16][17][18][19][20][21] such as MacMillan, Trost, Zhang, You and Zhao et al To our knowledge, most routes often relied on substituted indoles or tryptophan derivatives as starting materials, however, only a few reports were based on non-indole or nonoxindole. [15,[22][23][24] To address these limitations, Zhang group [25][26][27][28][29] has developed a novel copper(I)-catalyzed tandem reaction strategy to achieve several natural products of hexahydropyrroloindole alkaloids, such as (À )-Debromoflustramine E, (+)-Chimonanthine, (À )-Ditryptophenaline and (+)-Nocardioazine B et al Based on previous work, to continue our interest in studying the total synthesis of Hexahydropyrroloindole (HPI) alkaloids, herein we report a complementary route for the total synthesis of Flustramine B and Debromoflustramine B via a cascade cyclization process starting from non-indole or non-oxindole catalyzed by Copper (I).…”