Asymmetric Cycloaddition and Cyclization Reactions Catalyzed by Chiral N,N′-Dioxide–Metal Complexes

Abstract

Catalytic asymmetric cycloadditions and cascade cyclizations are a major focus for the enantioselective construction of chiral carbo- and heterocycles. A number of chiral Lewis acids and organocatalysts have been designed for such reactions. The development of broadly applicable catalysts bearing novel chiral backbones to meet the demands of various applications is an ongoing challenge. Approximately 10 years ago, we introduced a group of conformationally flexible C-symmetric N,N'-dioxide amide compounds, which represent a new class of privileged ligands. The coordination of the four oxygens of a chiral N,N'-dioxide around a central metal generates an octahedral tricyclometalated Lewis acid catalyst that can carry out various enantioselective reactions. In this Account, we summarize our recent studies on asymmetric cycloadditions between various dienophiles and dienes, dipoles and dipolarophiles, and cascade cyclizations catalyzed by chiral N,N'-dioxide-metal complexes. In principle, these unique chiral catalysts lower the LUMO energy of electron-deficient 2π components or heterodienes by coordination with the functional groups via various binding modes. With N-Boc-3-alkenyloxindole and alkylidene malonate as the electron-deficient 2π components, N,N'-dioxide-metal complexes provided excellent catalytic activities and asymmetric inductions for a variety of transformations, including [2 + 1], [3 + 2], [4 + 2], and [8 + 2] cycloadditions. Mechanistically, these substrates could be efficiently activated through bidentate coordination. The strategy was also useful for asymmetric cascade cyclizations to form polycyclic adducts. Monodentate or bidentate coordination of other α,β-unsubstituted carbonyl compounds to metal centers enabled both normal Diels-Alder reactions and inverse-electron-demand hetero-Diels-Alder reactions as well as [2 + 2] additions. Furthermore, hetero-Diels-Alder reactions of aldehydes, ketones, and imines are well-tolerated and afford various heterocycles. This includes allowing the concise synthesis of the antimalarial compound KAE609. Asymmetric Michael/cyclization reactions of bidentate α,β-unsaturated pyrazolamides gave efficient access to the chiral drugs (-)-paroxetine and (R)-thiazesim. The formal [3 + 2] cycloadditions of donor-acceptor epoxides and aziridines enantioselectively gave a series of five-membered oxo- and aza-heterocycles. The reaction of cyclopropane diketones showed unprecedented reactivities and provided a new route for the synthesis of dihydropyrrole and benzimidazole derivatives. General models for the catalytic reactions emerged from knowledge of the absolute configurations of the products of several reactions and X-ray crystal structures of the catalysts. In the field of chirality created by the coordination of an N,N'-dioxide to a metal center, the bonding of one or two reactants establishes a perfect reaction template for generation of the target adducts. Representative examples have been used to demonstrate how the substructures of the ligands and other reaction co...

RhII/ZnII Catalyzed Asymmetric [4+3] Cycloaddition Reaction

“…双金属接力催 化近年来也引起了有机化学家们的关注 [6] . 2013 年, Suga 课题组 [7] 四川大学化学学院冯小明研究团队 [8] 种类多样的不对称催化反应. 另外, 该手性双氮氧-金 属配合物能够与多种过渡金属良好兼容, 可用于发展双 金属接力催化的不对称反应 [9] .…”

Synthesis of 1,2,3,4‐Tetrahydrobenzofuro[3,2‐d]pyrimidines via [4+2] Annulation Reaction of 1,3,5‐Triazinanes and Aurone‐Derived α,β‐Unsaturated Imines

“…[13] Thus far, to the best of our knowledge, there is no report on the annulation reaction between 1,3,5-triazinanes and aurone-derived azadienes, although this kind of [4 + 2] cycloaddition reaction of 1,3,5-triazinanes with aza-ortho-quinone methides/para-quinone methides has been disclosed recently. [8h-j] Continuing our ongoing interest in developing catalyst-free reactions, [14] we wonder whether these azadienes could react with 1,3,5-triazinanes via a [4 + 2] annulation pathway [15] to deliver 1,2,3,4-tetrahydrobenzofuro [3,2-d]pyrimidines, which will broaden the utility of 1,3,5-triazinanes in synthesizing azaheterocycles and deliver structurally novel 1,2,3,4tetrahydrobenzofuro [3,2-d]pyrimidines with potential bioactivities. Herein, we will describe our preliminary results on this subject.…”

Bimetallic Catalytic Asymmetric Tandem Reaction of β‐Alkynyl Ketones to Synthesize 6,6‐Spiroketals

“…Herein, we report the asymmetric synthesis of chiral 6,6spiroketal derivatives through Au III -catalyzed cycloisomerization of b-alkynyl ketones and subsenquent chiral N,N'dioxide-Mg(OTf) 2 complex-mediated [4+ +2] cycloaddition with b,g-unsaturated a-ketoesters (Scheme 1c). [11] In the initial examination, b,g-unsaturated a-ketoester 1a and b-alkynyl ketone 2a were selected as the standard substrates to optimize the reaction conditions.Inthe presence of AuCl 3 ,varieties of metal salts,such as Zn(OTf) 2 ,Sc(OTf) 3 , Yb(OTf) 3 ,a nd Mg(OTf) 2 coordinated with N,N'-dioxide ligand l l-RaPr 3 could promote the tandem cycloisomerization/[4+ +2] cycloaddition in CH 2 Cl 2 with 5 M. S. as the additive (Table 1, entries 1-4). Thedesired spiroketal 3a was obtained in 91 %y ield with 93 % ee (entry 4).…”