Enantioselective [2+2] Cycloaddition of Allenyl Imide with Mono- or Disubstituted Alkenes.

An efficient catalytic asymmetric [2+2] cycloaddition of allenyl imide and mono- or disubstituted alkenes is disclosed. The key feature of this method is the use of bidentate allenyl imide and weakly activated and less steric hindered alkene pair by utilizing chiral magnesium(II) complex of N,N'-dioxide, which could provide through-space dispersion interactions to orientate the arrangement of the alkene. This protocol allows the generation of a series of axially chiral cyclobutenes and four-membered ring-containing spirocycles (80 examples) in high yield (up to 99 %) with excellent enantioselectivity (up to >99 % ee), and the late-stage modification of biologically active molecules as well. Experimental studies and DFT calculations revealed that this [2+2] cycloaddition proceeded via a stepwise mechanism involving a short-lived zwitterionic intermediate. The π-π interaction between the alkenes and the amide moiety in the ligand was crucial for the enantiocontrol.

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

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.

Enantioselective Formal [4 + 2] Annulation of ortho-Quinone Methides with ortho-Hydroxyphenyl α,ß-Unsaturated Compounds.

The highly efficient enantioselective [4 + 2] cycloaddition of o-QMs with ortho-hydroxyphenyl-substituted α,ß-unsaturated compounds was realized by using a chiral N, N'-dioxide-Sc(III) complex as catalyst. A variety of chiral chromane derivatives with three continuous stereocenters were obtained in excellent results (up to 99% yield, >19:1 dr, and 99% ee) under as low as 0.005-1 mol % catalyst loading. Besides, a catalytic cycle with a possible transition state model was proposed to elucidate the origin of the chirality.

Catalytic Asymmetric Synthesis of Axially and Centrally Chiral 1,2-Dihydrobenzofuro[3,2-b]pyridines through a [2 + 2] Cycloaddition/Retroelectrocyclization/Re-Cycloaddition Cascade.

A catalytic asymmetric tandem cyclization of azadienes and ortho-alkynylnaphthols accelerated by the chiral N,N'-dioxide-gadolinium(III) complex is disclosed. This method allows the synthesis of a range of 1,2-dihydrobenzofuro[3,2-b]pyridines containing both axially and centrally chiral elements in high yields and excellent stereoselectivities (up to >99% yield, 91:9 dr, 98% ee). A control experiment revealed that this process proceeded through a multistep [2 + 2] cycloaddition/retroelectrocyclization/tautomerism/1,6-conjugate addition cascade.

Asymmetric synthesis of complex tricyclo[3.2.2.0]nonenes from racemic norcaradienes: kinetic resolution via Diels-Alder reaction.

Herein, the enantioselective synthesis of complex tricyclo[3.2.2.0]nonenes through the Diels-Alder reaction is reported. Utilizing racemic norcaradienes prepared from the visible-light-mediated dearomative cyclopropanation of m-xylene as dienes and enone derivatives as dienophiles, the overall process represents a kinetic asymmetric transformation in the presence of a chiral cobalt(ii) complex of chiral N,N'-dioxide. High diastereo- and enantioselectivity could be obtained in most cycloaddition processes and part racemization of norcaradiene is observed. The topographic steric maps of the catalysts were collected to rationalize the relationship between reactivity and enantioselectivity with the catalysts.

Catalytic enantioselective synthesis of macrodiolides and their application in chiral recognition.

New types of C 2-symmetric chiral macrodiolides are readily obtained via chiral N,N'-dioxide-scandium(iii) complex-promoted asymmetric tandem Friedel-Crafts alkylation/intermolecular macrolactonization of ortho-quinone methides with C3-substituted indoles. This protocol provides an array of enantioenriched macrodiolides with 16, 18 or 20-membered rings in moderate to good yields with high diastereoselectivities and excellent enantioselectivities through adjusting the length of the tether at the C3 position of indoles. Density functional theory calculations indicate that the formation of macrocycles is more favorable than that of 9-membered-ring lactones in terms of kinetics and thermodynamics. The potential utility of these intriguing chiral macrodiolide molecules is demonstrated in the enantiomeric recognition of aminols and chemical recognition of metal ions.