Planar Chirality: A Mine for Catalysis and Structure Discovery

Abstract

Planar chirality is one of the most fascinating expressions of chirality, which is exploited by nature to lock three-dimensional chiral conformations and, more recently, by chemists to create new chiral reagents, catalysts, and functional organic materials. Nevertheless, the shortage of procedures able to induce and secure asymmetry during the generation of these unique chiral entities has dissuaded chemists from exploiting their structural properties. This Minireview intends to illustrate the limited but remarkable catalytic methods that have been reported for the production of planar chirality in strained molecules and serve as a source of inspiration for the development of new unconventional procedures, which are expected to appear in the near future.

Keywords: asymmetric catalysis; atropisomerism; cyclophanes; macrocyclization; planar chirality.

Figure 1

Selected examples of natural and artificial molecules exhibiting planar chirality only.

Figure 2

Frequent cyclophane prototypes with planar chirality.

Scheme 1

Stereoselective ring‐closing metathesis towards [10]‐ and [12]paracyclophanes.

Scheme 2

Catalytic enantioselective routes for the synthesis of planar‐chiral cyclophanes.

Scheme 3

Construction of chiral [7.7]paracyclophanes through catalytic asymmetric Sonagashira coupling of racemic diiodoparacyclophanes.

Scheme 4

Catalytic enantioselective lithiation and dilithiation of dioxa[10]paracyclophanes and dioxa[11]paracyclophanes.

Scheme 5

Gram‐scale synthesis of enantipure [2.2]paracyclophane 18 by catalytic ATH desymmetrization. DPEN: 1,2‐diphenyl‐1,2‐ethylenediamine.

Scheme 6

Rhodium‐catalyzed synthesis of enantioenriched dithia[n]paracyclophanes (n=9, 10, 12) and dithia[3.3]paracyclophanes.

Scheme 7

Synthesis of enantioenriched natural diaryl ether heptanoids by enantioselective Ullman ether coupling.

Scheme 8

Pd‐catalyzed enantioselective synthesis of planar‐chiral cyclic amides and the transition‐state model that explains the stereoselectivity. Yields determined by ¹H NMR spectroscopy. ND: absolute configuration not determined.

Scheme 9

a) Enantioselective synthesis of chiral [7]–[10]metacyclophanes through rhodium‐catalyzed alkyne cyclotrimerization. b) Proposed reaction intermediate.

Scheme 10

Enantioselective synthesis of chiral tripodal cage compounds 37 by rhodium‐catalyzed cyclotrimerization of nitrogen‐branched triynes. DCE: 1,2‐dichloroethane.

Scheme 11

Enantioselective synthesis of [10]‐ and [12]paracyclophanes by rhodium‐catalyzed [2+2+2]cycloaddition of cyclic diynes with terminal monoynes.

Scheme 12

Selected examples of the enantioselective synthesis of PAH‐based planar chiral bent cyclophanes. DDQ: 2,3‐dichloro‐5,6‐dicyano‐1,4‐benzoquinone.

Scheme 13

Enantioselective synthesis of planar‐chiral zigzag‐type [8]cyclophenylene belt 47. Segphos: 5,5′‐bis(diphenylphosphino)‐4,4′‐bi‐1,3‐benzodioxole.

Scheme 14

Planar to planar chirality transfer in the photoisomerization of cyclooctenes. 2MB: 2‐methylbutane; MCH: methylcyclohexane.

Scheme 15

Enantioselective synthesis of chiral cyclic amide 50.

Scheme 16

Asymmetric PTC‐catalyzed synthesis of diaryl ether cyclophane skeletons.

Scheme 17

a) Reaction conditions for the biocatalytic synthesis of chiral [12]‐, [13]‐, [14]‐, and [15]paracyclophanes. b) Mechanism of the acylation reaction promoted by the Ser‐His‐Asp catalytic triad and the oxyanion hole. c) Selected examples of the atroposelective macrocyclization.

Figure 3

Planar‐chiral “triceptide” 61 and planar‐chiral cyclophane 62 post‐translationally produced in bacteria. The C−C bonds forming the cyclophanes are marked in gray.