Phosphine-Catalyzed Annulations of Azomethine Imines: Allene-Dependent [3 + 2], [3 + 3], [4 + 3], and [3 + 2 + 3] Pathways

Abstract

In this paper we describe the phosphine-catalyzed [3 + 2], [3 + 3], [4 + 3], and [3 + 2 + 3] annulations of azomethine imines and allenoates. These processes mark the first use of azomethine imines in nucleophilic phosphine catalysis, producing dinitrogen-fused heterocycles, including tetrahydropyrazolo-pyrazolones, -pyridazinones, -diazepinones, and -diazocinones. Counting the two different reaction modes in the [3 + 3] cyclizations, there are five distinct reaction pathways—the choice of which depends on the structure and chemical properties of the allenoate. All reactions are operationally simple and proceed smoothly under mild reaction conditions, affording a broad range of 1,2-dinitrogen–containing heterocycles in moderate to excellent yields. A zwitterionic intermediate formed from a phosphine and two molecules of ethyl 2,3-butadienoate acted as a 1,5-dipole in the annulations of azomethine imines, leading to the [3 + 2 + 3] tetrahydropyrazolodiazocinone products. The incorporation of two molecules of an allenoate into an eight-membered-ring product represents a new application of this versatile class of molecules in nucleophilic phosphine catalysis. The salient features of this protocol—the facile access to a diverse range of nitrogen-containing heterocycles and the simple preparation of azomethine imine substrates—suggest that it might find extensive applications in heterocycle synthesis.

4.22 Intermolecular 1,3-Dipolar Cycloadditions of Alkenes, Alkynes, and Allenes

“…85 The reaction proceeds smoothly under mild reaction conditions, furnishing a broad range of 1,2-dinitrogen-containing heterocycles 152 in moderate to excellent yield. In the use of enantioenriched chiral phosphines 153, the asymmetric version of this reaction has been realized, giving the corresponding cycloadduct in 56% yield with 89% ee.…”

N‐Imide Ylide‐Based Reactions: CH Functionalization, Nucleophilic Addition and Cycloaddition

“…Other compounds with unsaturated bonds, such as allenoates [35][36] and activated alkenes, [37] were evaluated as well. Uncatalyzed or PA C H T U N G T R E N N U N G (t-Bu) 3 -catalyzed [3+2] cyclization of azomethine imine ylides 56 and 78 were described by Kwon 35 and Guo, [36] respectively.…”

“…Uncatalyzed or PA C H T U N G T R E N N U N G (t-Bu) 3 -catalyzed [3+2] cyclization of azomethine imine ylides 56 and 78 were described by Kwon 35 and Guo, [36] respectively. The transformation showed high efficiency and excellent functional group tolerance (Scheme 23).…”

“…[86] 4. . [35] The phosphine-catalyzed reaction of In 2013, the [4+3] cyclization of C,N-cyclic azomethine imine 218 with in situ generated azoalkene 224 was reported by Xiao. The reaction proceeded without any catalyst, providing an efficient and mild approach to the functionalized 1,2,4,5-tetrazepine deriv-atives 222.…”

A DFT study on the competing mechanisms of PPh3-catalyzed [3+3] and [3+2] annulations between 5-acetoxypenta-2,3-dienoate and 1C,3O-bisnucleophiles

“…In 2003, Zhu et al firstly reported the [4 + 2] annulation reaction of allenoates and N-tosylbenzaldimines to form functionalized tetrahydropyridines [25], which leads to the large-scale applications of the phosphinecatalysts. Since the pioneer work of Lu and Kwon are reported, many efforts have been devoted to improve and develop various kinds of the phosphine-catalyzed reactions [2,12,[26][27][28][29][30][31][32][33][34][35][36][37][38][39]. In 2009, Kwon reported phosphine-catalyzed [3 + 3] annulations of aziridines and allenoates to get azidirines in room temperature [40].…”