An enantioselective C-H arylation of phosphine oxides with o-quinone diazides catalyzed by an iridium(III) complex bearing an atropchiral cyclopentadienyl (Cp ) ligand and phthaloyl tert-leucine as co-catalyst is reported. The method allows access to a) P-chiral biaryl phosphine oxides, b) atropo-enantioselective construction of sterically demanding biaryl backbones, and also c) selective assembly of axial and P-chiral compounds in excellent yields and diastereo- and enantioselectivities. Enantiospecific reductions provide monodentate chiral phosphorus(III) compounds having structures and biaryl backbones with proven importance as ligands in asymmetric catalysis.

Cyclopropanes fused to pyrrolidines are important structural features found in a number of marketed drugs and development candidates. Typically, their synthesis involves the cyclopropanation of a dihydropyrrole precursor. Reported herein is a complementary approach which employs a palladium(0)-catalyzed C-H functionalization of an achiral cyclopropane to close the pyrrolidine ring in an enantioselective manner. In contrast to aryl-aryl couplings, palladium(0)-catalyzed C-H functionalizations involving the formation of C(sp(3) )-C(sp(3) ) bonds of saturated heterocycles are very scarce. The presented strategy yields cyclopropane-fused γ-lactams from chloroacetamide substrates. A bulky Taddol phosphonite ligand in combination with adamantane-1-carboxylic acid as a cocatalyst provides the γ-lactams in excellent yields and enantioselectivities.

β-Lactams are very important structural motifs because of their broad biological activities as well as their propensity to engage in ring-opening reactions. Transition-metal-catalyzed C-H functionalizations have emerged as strategy enabling yet uncommon highly efficient disconnections. In contrast to the significant progress of Pd(0)-catalyzed C-H functionalization for aryl-aryl couplings, related reactions involving the formation of saturated C(sp(3))-C(sp(3)) bonds are elusive. Reported here is an asymmetric C-H functionalization approach to β-lactams using readily accessible chloroacetamide substrates. Important aspects of this transformation are challenging C(sp(3))-C(sp(3)) and strain-building reductive eliminations to for the four-membered ring. In general, the β-lactams are formed in excellent yields and enantioselectivities using a bulky taddol phosphoramidite ligand in combination with adamantyl carboxylic acid as cocatalyst.

Monodentate TADDOL-derived phosphoramidites and phosphonites are versatile chiral ligands for enantioselective Pd(0)-catalysed C-H functionalisations. They enable highly selective cyclisations to access a wide range of chiral carbo- and heterocycles. The high attractiveness of this ligand class consists in their modular structure, allowing for a quick assembly of a library with variable steric properties. Asymmetric C-H functionalisation methods utilising catalytic systems based on Pd(0) complexes and TADDOL-type ligands are presented and aspects of selectivity are discussed.

Enantioselective palladium(0)-catalyzed C–H arylations of cyclopropanes provide efficient access to dihydroquinolones, dihydroisoquinolones and the BMS-791325 indolobenzazepine core.