Metal complexes coordinated by a single cyclopentadienyl (Cp) ligand are widely used, versatile catalysts, but their application to asymmetric reactions has been hindered by the difficulty of designing Cp substituents that effectively bias the coordination sphere. Here, we report on a class of simple C(2)-symmetric Cp derivatives that finely control the spatial arrangement of the transiently coordinated reactants around the central metal atom. Rhodium(III) complexes bearing these ligands proved to be highly enantioselective catalysts for directed carbon-hydrogen (C-H) bond functionalizations of hydroxamic acid derivatives.

The lack of robust and tunable chiral versions of cyclopentadienyl (Cp) ligands hampers progress in the development of catalytic asymmetric versions of a myriad of reactions catalyzed by this ubiquitous ligand. Herein, we describe of a class of chiral Cp ligands with tunable steric parameters. Coordinated to transition metals, the ligand creates a well-defined chiral pocket, able to imprint its chirality onto the metal. The corresponding Rh complexes are shown to be excellent catalysts for enantioselective allylation of N-methoxybenzamides via directed C-H functionalizations at very mild conditions. The obtained enantioselectivities are excellent and demonstrate the viability of chiral Cp complexes as selective transition metal catalysts.

Transition-metal catalyzed C-H functionalizations became a complementary and efficient bond-forming strategy over the past decade. In this respect, Cp*Rh(III) complexes have emerged as powerful catalysts for a broad spectrum of reactions giving access to synthetically versatile building blocks. Despite their high potential, the corresponding catalytic enantioselective transformations largely lag behind. The targeted transformations require all the remaining three coordination sites of the central rhodium atom of the catalyst. In consequence, the chiral information on a competent catalyst can only by stored in the cyclopentadienyl unit. The lack of suitable enabling chiral cyclopentadienyl (Cp(x)) ligands is the key hurdle preventing the development of such asymmetric versions. In this respect, an efficient set of chiral Cp(x) ligands useable with a broad variety of different transition-metals can unlock substantial application potential. This Account provides a description of our developments of two complementary classes of C2-symmetric Cp(x) derivatives. We have introduced a side- and back-wall concept to enforce chirality transfer onto the central metal atom. The first generation consists of a fused cyclohexane unit having pseudo axial methyl groups as chiral selectors and a rigidifying acetal moiety. The second ligand generation derives from an atrop-chiral biaryl-backbone and which possesses adjustable substituents at its 3,3'-positions. Both ligand families can be modulated in their respective steric bulk to adjust for the specific needs of the targeted application. The cyclopentadienes can be metalated under standard conditions. The corresponding chiral rhodium(I) ethylene complexes are relatively air and moisture and represent storable stable precatalysts for the targeted asymmetric Rh(III)-catalyzed C-H functionalizations. These complexes are then conveniently oxidized in situ by dibenzoyl peroxide to give the reactive Cp(x)Rh(III)(OBz)2 species. For instance, this catalyst is used for directed C-H activations of aryl hydroxamates and the subsequent enantioselective trapping with olefins, providing dihydroisoquinolones in very high enantioselectivities. In addition, we have established highly selective intramolecular trapping reactions with tethered higher substituted alkenes giving dihydrobenzofurans with quaternary stereogenic centers. Concerning intermolecular reactions, allene coupling partners allow for an enantioselective hydroarylation yielding substituted allylated compounds. A trapping process of the cyclometalated intermediate with diazo reactants enables the enantioselective construction of isoindolinones. Moreover, the catalysts can be used for the construction of atropchiral biaryl motives using a dehydrogenative Heck-type reaction. The development of flexibly adjustable chiral Cp(x) ligands is described in this Account showcasing their applicability for a variety of Rh(III) catalyzed C-H functionalization reactions. These Cp(x) derivatives hold promise as powerful steering ligands for furthe...

Metal-catalyzed functionalizations at the ortho position of a directing group have become an efficient bond-forming strategy. A wide range of transformations that employ Cp*Rh(III) catalysts have been described, but despite their synthetic potential, enantioselective variants that use chiral versions of the Cp* ligand remain scarce (Cp*=pentamethyl cyclopentadienyl). Cyclopentadienyl compounds with an atropchiral biaryl backbone are shown to be suitable ligands for the efficient intramolecular enantioselective hydroarylation of aryl hydroxamates. Dihydrofurans that bear methyl-substituted quaternary stereocenters are thus obtained by CH functionalization under mild conditions.

Director's cut: The pharmaceutically relevant sulfonamide group is shown to be a competent directing group for [Cp*Rh(OAc)(2)]-catalyzed C-H functionalizations. Reactions of the cyclometalated intermediate with internal alkynes provide access to a wide range of sultam derivatives. The reaction is high yielding and works best under aerobic conditions with catalytic amounts of CuOAc as an oxidation mediator. Cp* = C(5)Me(5).