General Methods Experimental Procedures, Reagents and Glassware All commercially available chemicals were used as purchased for the synthesis of substrates. All reactions were carried out under an atmosphere of nitrogen in oven-dried glassware with magnetic stirring, unless otherwise indicated. Acetonitrile (MeCN) was dried over CaH2, distilled and stored inside the N2-filled glovebox. Toluene, THF and dichloromethane were purified by the Innovative Technology Solvent Delivery System. Chemicals were used as obtained from the suppliers unless otherwise stated. Solvent compositions are given in (v/v). Chromatography Flash chromatography was performed with Silicycle silica gel 60 (0.040-0.063 μm grade). Analytical thin-layer chromatography was performed with commercial glass plates coated with 0.25 mm silica gel (E. Merck, Kieselgel 60 F254). Compounds were visualized under UV-light at 254 nm and oxidized in standard KMnO4 dye followed by heating if necessary. NMR Spectroscopy Proton nuclear magnetic resonance (1 H NMR) data were acquired at 400 MHz on a Bruker AVANCEIII-400 spectrometer or at 600 MHz on a Bruker DRX-600 spectrometer. Chemical shifts (δ) are reported in parts per million (ppm) relative to residual chloroform (s, 7.26 ppm) or residual acetone (2.05 ppm). Proton decoupled Carbon-13 nuclear magnetic resonance (13 C NMR) data were acquired at 101 MHz or 126 MHz on a Bruker AVANCEIII-400. Chemical shifts are reported in ppm relative to residual chloroform (77.16 ppm) or residual acetone (29.84 ppm, 206.26 ppm). Proton decoupled Fluorine-19 nuclear magnetic resonance (19 F{ 1 H} NMR) were acquired at 377 MHz on a Bruker AV400 spectrometer. Proton decoupled Phosphorus-31 nuclear magnetic resonance (31P{1H} NMR) were acquired at 162 MHz on a Bruker AV400 spectrometer. The assignment of proton and carbon signals was assisted by COSY, HSQC, HMBC and DEPT-135 experiments where necessary. Splitting patterns are designated as s, singlet; d, doublet; t, triplet; q, quartet; p, pentet; hept, heptet; dd, doublet of doublets; dt, doublet of triplets; ddd, doublet of doublets of doublets; tt, triplet of triplets; tq, triplet of quartets; qt, quartet of triplets; m, multiplet. All NMR data were recorded at 298 K. Infrared Spectroscopy Infrared (IR) data were recorded on an Alpha-P Bruker FT-IR Spectrometer. Absorbance frequencies are reported in reciprocal centimeters (cm-1). Mass Spectrometry HRMS measurements were performed on an Agilent LC-MS TOF (Multimode: ESI + APCI + APPI). High resolution mass are given in m/z. Melting Points Melting points were measured on a Büchi B-540 and are uncorrected. Enantiomeric excesses Enantiomeric excesses were measured on an Agilent HPLC and Shimadzu HPLC. Optical rotations were measured on a Polartronic M polarimeter using a 0.5 cm cell with a Na 589 nm filter.

A bioinspired enantioselective synthesis of crinine-type alkaloids was developed by iridium-catalyzed asymmetric hydrogenation of enones, providing 24 crinine-type alkaloids and 8 analogues with high yield and high enantioselectivity.

(+)-Gracilamine, a biologically attractive and structurally unique pentacyclic Amaryllidaceae alkaloid, was biomimetically synthesized in 11 linear steps in 9.9% overall yield from the known racemic oxocrinine. The synthesis features an asymmetric hydrogenation, a ring-opening/benzylic oxidation/cyclization sequence, and a biomimetic intramolecular cycloaddition. This total synthesis not only allows the assignment of its absolute configuration, but also provides experimental support for the hypothesis that naturally occurring (+)-gracilamine is biogenetically derived from the crinine-type alkaloid (+)-epivittatine.

The three-dimensional structure of carbohelicenes has fascinated generations of molecular chemists and has been exploited in a wide range of applications. Their strong circularly polarized luminescence has attracted considerable attention in recent years due to promising applications in new optical materials. Although the enantioselective synthesis of fused carbo- and heterohelicenes has been achieved, a direct catalytic enantioselective method allowing the synthesis of lower, non-fused carbo[n]helicenes (n = 4–6) is still lacking. We report here that Pd-catalysed enantioselective C–H arylation in the presence of a unique bifunctional phosphine-carboxylate ligand provides a simple and general access to these lower carbo[n]helicenes. Computational mechanistic studies indicate that both the C–H activation and reductive elimination steps contribute to the overall enantioselectivity. The observed enantio-induction seems to arise from a combination of non-covalent interactions and steric repulsion between the substrate and ligand during the two key reductive elimination steps. The photophysical and chiroptical properties of the synthesized scalemic [n]helicenes have been systematically studied.

The unique three-dimensional structure of carbohelicenes have fascinated generations of molecular chemists and has been exploited through a wide range of applications. In particular, their strong circularly polarized luminescence (CPL) has raised much attention in recent years due to promising applications in the design of new optical materials. Whereas a number of important precedents report enantioselective syntheses of fused carbo- and heterohelicenes, a direct catalytic enantioselective method allowing the synthesis of lower, nonfused carbo[n]helicenes (n = 4-6) is still lacking. We report that Pd-catalysed enantioselective C–H arylation in the presence of a unique bifunctional phosphine-carboxylate ligand provides a simple and general access to these simple carbo[n]helicenes. Computational mechanistic studies indicate that both the C–H activation and reductive elimination steps contribute to the overall enantioselectivity. In addition, the observed enantio-induction seems to arise from a combination of noncovalent interactions and steric repulsion between the substrate and ligand during the two key reductive elimination steps. Moreover, the current method allows a comparative study of the CPL properties of lower carbo[n]helicenes, which led to the discovery that carbo[4]helicenes actually display CPL responses comparable to the higher carbo[6]helicene congeners.