Oppolzer-Type Intramolecular Diels–Alder Cycloadditions via Isomerizations of Allenamides

Abstract

A new approach to Oppolzer!s intramolecular Diels-Alder cycloaddition [IMDA] through γ–isomerization of readily available N-tethered allenamides is described. These IMDA reactions are carried out in tandem with the allenamide isomerization or 1,3-H shift, leading to complex nitrogen heterocycles in a highly stereoselective manner.

Allenamides: A Powerful and Versatile Building Block in Organic Synthesis

“…Hsung 156 utilized the 1,3-H shift from the γ-position of allenamide for Oppolzer-type intramolecular Diels-Alder cycloadditions (Scheme 167). Fully functionalized allenamide 611 could be prepared from the copper catalyzed coupling between amide 609 and 1-iodoallene 610 .…”

Recent progress in transition-metal-free functionalization of allenamides

“…Hsung 33 further developed a new approach to Oppolzer's intramolecular Diels-Alder cycloaddition (IMDA) through the gisomerization of readily available N-tethered allenamides 99. These IMDA reactions are performed in tandem with the allenamide isomerization or 1,3-H shi, via an endo-transition state, as shown in Scheme 26, leading to complex nitrogen heterocycles 100 in a highly stereoselective manner.…”

Gold‐Catalyzed Asymmetric Intramolecular Cyclization of N‐Allenamides for the Synthesis of Chiral Tetrahydrocarbolines

“…Next, we attempted the reactions of α‐ or γ‐substituted N‐allenamides (Scheme ). The reaction of γ‐disubstituted N‐allenamide 1 v gave the desired product 2 v but in only 15 % yield with 30 % ee , and 1‐amido diene 2 v ′′ was produced as the major product through isomerization under the standard conditions ,. Notably, the cycloaddition product 2 v′′ was obtained in 49 % ee when using the ( S,S,S )‐ Ls ‐ 25 ligand .…”

“…The reaction of γ‐disubstituted N‐allenamide 1 v gave the desired product 2 v but in only 15 % yield with 30 % ee , and 1‐amido diene 2 v ′′ was produced as the major product through isomerization under the standard conditions ,. Notably, the cycloaddition product 2 v′′ was obtained in 49 % ee when using the ( S,S,S )‐ Ls ‐ 25 ligand . The temperature was raised to 80 °C for the cyclization of α‐substituted N‐allenamide 1 w , leading to the desired cyclization product 2 w in 45 % yield in only 2 % ee and a trace amount of dinene 2 w′′ (see other conditions in the Supporting Information)…”