Recent Advances of Catalytic Asymmetric 1,3-Dipolar Cycloadditions

Recent developments in catalytic asymmetric inverse-electron-demand Diels-Alder reaction.

Transition-metal catalyzed reactions that are able to construct complex aliphatic amines from simple, readily available feedstocks have become a cornerstone of modern synthetic organic chemistry. I...

New Strategies for the Transition-Metal Catalyzed Synthesis of Aliphatic Amines.

Formal [4+1] Annulation Reactions in the Synthesis of Carbocyclic and Heterocyclic Systems

Catalytic asymmetric synthesis of spirooxindoles: recent developments

ConspectusCatalytic 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 C2-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 uniq...

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

A general and practical strategy for remote site-selective functionalization of unactivated aliphatic C-H bonds in various amides by radical chemistry is introduced. C-H bond functionalization is achieved by using the readily installed N-allylsulfonyl moiety as an N-radical precursor. The in situ generated N-radical engages in intramolecular 1,5-hydrogen atom transfer to generate a translocated C radical which is subsequently trapped with various sulfone reagents to afford the corresponding C-H functionalized amides. The generality of the approach is documented by the successful remote C-N3 , C-Cl, C-Br, C-SCF3 , C-SPh, and C-C bond formation. Unactivated tertiary and secondary C-H bonds, as well as activated primary C-H bonds, can be readily functionalized by this method.

Site‐Selective Remote Radical C−H Functionalization of Unactivated C−H Bonds in Amides Using Sulfone Reagents

An asymmetric aza-Diels-Alder reaction of 3-vinylindoles with isatin-derived ketimines has been developed. A series of spiroindolone derivatives were thus obtained in good to excellent yields with excellent enantioselectivity (up to 96 % yield and 99 % ee). Furthermore, the antimalarial compound NITD609 could be obtained in three steps with an overall yield of 40.6 %. Control experiments and operando IR experiments imply a concerted reaction pathway. The regioselectivity and exo selectivity result from π-π interactions between the two indoline rings of the two reactants.

Regio- and Enantioselective Aza-Diels–Alder Reactions of 3-Vinylindoles: A Concise Synthesis of the Antimalarial Spiroindolone NITD609

The asymmetric ring-opening/cyclization of cyclopropyl ketones with primary amine nucleophiles was catalyzed by a chiral N,N′-dioxide/scandium(III) complex through a kinetic resolution process. A broad range of cyclopropyl ketones and primary amines are suitable substrates of this reaction. The corresponding products were afforded in excellent enantioselectivities and yields (up to 97 % ee and 98 % yield) under mild reaction conditions. This method provides a promising access to chiral 2,3-dihydropyrroles as well as an effective procedure for the kinetic resolution of 2-substituted cyclopropyl ketones.

Asymmetric synthesis of 2,3-dihydropyrroles by ring-opening/cyclization of cyclopropyl ketones using primary amines.

A highly efficient asymmetric ring-opening reaction of cyclopropyl ketones with a broad range of thiols, alcohols and carboxylic acids has been first realized by using a chiral N,N'-dioxide-scandium(III) complex as catalyst. The corresponding sulfides, ethers, and esters were obtained in up to 99% yield and 95% ee. This is also the first example of one catalytic system working for the ring-opening reaction of donor-acceptor cyclopropanes with three different nucleophiles, let alone in an asymmetric version.

Asymmetric Ring-Opening of Cyclopropyl Ketones with Thiol, Alcohol, and Carboxylic Acid Nucleophiles Catalyzed by a Chiral N,N'-Dioxide-Scandium(III) Complex

Yong Xia

Papers

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

Site‐Selective Remote Radical C−H Functionalization of Unactivated C−H Bonds in Amides Using Sulfone Reagents

Regio- and Enantioselective Aza-Diels–Alder Reactions of 3-Vinylindoles: A Concise Synthesis of the Antimalarial Spiroindolone NITD609

Asymmetric synthesis of 2,3-dihydropyrroles by ring-opening/cyclization of cyclopropyl ketones using primary amines.

Asymmetric Ring-Opening of Cyclopropyl Ketones with Thiol, Alcohol, and Carboxylic Acid Nucleophiles Catalyzed by a Chiral N,N'-Dioxide-Scandium(III) Complex