Primary Anion–π Catalysis of Epoxide‐Opening Ether Cyclization into Rings of Different Sizes: Access to New Reactivity

Abstract

The concept of anion–π catalysis focuses on the stabilization of anionic transition states on aromatic π surfaces. Recently, we demonstrated the occurrence of epoxide‐opening ether cyclizations on aromatic π surfaces. Although the reaction proceeded through unconventional mechanisms, the obtained products are the same as those from conventional Brønsted acid catalysis, and in agreement with the Baldwin selectivity rules. Different mechanisms, however, should ultimately lead to new products, a promise anion–π catalysis has been reluctant to live up to. Herein, we report non‐trivial reactions that work with anion–π catalysis, but not with Brønsted acids, under comparable conditions. Namely, we show that the anion–π templated autocatalysis and epoxide opening with alcoholate–π interactions can provide access to unconventional ring chemistry. For smaller rings, anion–π catalysis affords anti‐Baldwin oxolanes, 2‐oxabicyclo[3.3.0]octanes, and the expansion of Baldwin oxetanes by methyl migration. For larger rings, anion–π templated autocatalysis is thought to alleviate the entropic penalty of folding to enable disfavored anti‐Baldwin cyclizations into oxepanes and oxocanes.

Anion-π Catalysis: A Novel Supramolecular Approach for Chemical and Biological Transformations

“…On the other hand, experimental studies have revealed that Michael-addition between malonic acid half thioester (37) and enolate acceptor 38 fails without anion-π catalyst and hence leads to solely the formation of a decarboxylation product 40. Fortunately, the presence of anion-π catalyst for the same reaction leads to the formation of an addition product (39) selectively in comparison to decarboxylation product (40) (Figure 5). [16] Besides these significant catalytic studies of anion-π interactions, the anion-π catalytic domain has now been explored to iminium, [18] enamine, [15] oxocarbenium, and transamination chemistry.…”

“…On the π-acidic surface of 13, they have carried out asymmetric addition of 54 to nitroolefin enamine acceptor 55. The NDI π-acidic surface helps in the stabilization of transition state of anion near nitronate intermediate by anion-π interactions as can be observed from the structures of Schematic depiction of addition product (39) selectivity over decarboxylated product (40) by means π-stacked foldamer assisted anion-(π) n -π catalysis.…”

“…Schematic illustration of addition product (39) and decarboxylation product (40) along with immobilized anion-π catalyst 51 and induced dipole (μz).…”

Pnictogen‐Bonding Catalysis: An Interactive Tool to Uncover Unorthodox Mechanisms in Polyether Cascade Cyclizations

“…This inversion of the head‐to‐tail directionality with 1,5 trans ‐diepoxide 3 to the tail‐to‐head directionality with 1,4 trans ‐diepoxide 11 was as designed. Namely, shortening of the tether of the alcohol nucleophile from three carbons in 4‐epoxyalcohol 3 to two carbons in 3‐epoxyalcohol 11 should disfavor head‐to‐tail cyclization into the smaller, more strained rings [18] . Instead, the central epoxide oxygen opens the pnictogen‐bonding activated terminal epoxide.…”

“…Namely, shortening of the tether of the alcohol nucleophile from three carbonsi n4 -epoxyalcohol 3 to two carbons in 3-epoxyalcohol 11 should disfavor head-to-tail cyclization into the smaller, more strained rings. [18] Instead, the central epoxide oxygen opens the pnictogen-bonding activated terminal epoxide. This tail-to-head cyclization occurs with anti-Baldwin endo-tet selectivity because the Baldwin isomer would be highly strained.…”