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

In recent decades, transient and highly reactive ortho-quinodimethanes (o-QDMs), ortho-quinone methides (o-QMs) and aza-ortho-quinone methides (aza-o-QMs) have attracted much attention and have been extensively studied and applied in organic synthesis, especially natural product total synthesis. This review summarizes recent advances in Diels–Alder reactions involving in situ-generated o-QDMs, o-QMs and aza-o-QMs, highlighting the power and potential of this strategy in organic synthesis and natural product total synthesis. An overview of the methods for generating these intermediates is also available.

Recent advances in the application of Diels-Alder reactions involving o-quinodimethanes, aza-o-quinone methides and o-quinone methides in natural product total synthesis.

Chiral Amino Acids‐Derived Catalysts and Ligands

The first catalytic asymmetric (4+3) cyclization of in situ generated ortho-quinone methides with 2-indolylmethanols has been established, which constructed seven-membered heterocycles in high yields (up to 95 %) and excellent enantioselectivity (up to 98 %). This approach not only represents the first catalytic asymmetric (4+3) cyclization of o-hydroxybenzyl alcohols, but also enabled an unprecedented catalytic asymmetric (4+3) cyclization of 2-indolylmethanols. In addition, a scarcely reported catalytic asymmetric (4+3) cyclization of para-quinone methide derivatives was accomplished.

Catalytic Asymmetric (4+3) Cyclizations of In Situ Generated ortho-Quinone Methides with 2-Indolylmethanols.

The Chemistry of organophosphorus compounds

Enantioselective synthesis of dihydrocoumarin derivatives by chiral scandium(III)-complex catalyzed inverse-electron-demand hetero-Diels-Alder reaction.

The asymmetric propargyl Claisen rearrangement provides a convenient entry to chiral allene motifs. Herein, we describe the development of a kinetic resolution and asymmetric rearrangement of racemic propargyl vinyl ethers. This transformation afforded chiral allene products along with the enantiomerically enriched substrate in good yields with excellent diastereo- and enantioselectivity. The complete chirality transfer and facially selective rearrangement enabled the simultaneous construction of an axially chiral allenic unit and a quaternary carbon stereocenter.

Synergistic Kinetic Resolution and Asymmetric Propargyl Claisen Rearrangement for the Synthesis of Chiral Allenes.

Highly efficient catalytic asymmetric Claisen rearrangements of O-propargyl -ketoesters and O-allyl -ketoesters have been accomplished under mild reaction conditions. In the presence of the chiral N,N-dioxide/Ni-II complex, a wide range of allenyl/allyl-substituted all-carbon quaternary -ketoesters was obtained in generally good yield (up to 99%) and high diastereoselectivity (up to 99:1 d.r.) with excellent enantioselectivity (up to 99% ee).

Nickel(II)-Catalyzed Asymmetric Propargyl and Allyl Claisen Rearrangements to Allenyl- and Allyl-Substituted β-Ketoesters†

Highly enantioselective [8+3] high-order cycloaddition reactions of tropones or azaheptafulvenes with meso-aziridines were achieved by a desymmetrization/annulation process in the presence of chiral N,N'-dioxide/Mg(OTf)2 complex. The corresponding tetrahydrocyclohepta[b][1,4]oxazines and tetrahydro-1H-cyclohepta- [b]-pyrazines were obtained in good yields (66-98 %) with excellent diastereo- and enantioselectivities (>19:1 d.r., 90-96 % ee). A possible transition state model was proposed to elucidate the origin of chiral induction based on the control experiments and X-ray crystal structure of the catalyst.

Haipeng Hu

Papers

Enantioselective synthesis of dihydrocoumarin derivatives by chiral scandium(III)-complex catalyzed inverse-electron-demand hetero-Diels-Alder reaction.

Synergistic Kinetic Resolution and Asymmetric Propargyl Claisen Rearrangement for the Synthesis of Chiral Allenes.

Nickel(II)-Catalyzed Asymmetric Propargyl and Allyl Claisen Rearrangements to Allenyl- and Allyl-Substituted β-Ketoesters†

Catalytic Asymmetric [8+3] Annulation Reactions of Tropones or Azaheptafulvenes with meso‐Aziridines

Enantioselective Vinylogous Michael-Aldol Reaction To Synthesize Spirocyclohexene Pyrazolones in Aqueous Media.