Chiral Cyclopentadienyl Ligands Enable a Rhodium(III)-Catalyzed Enantioselective Access to Hydroxychromanes and Phthalides

The demand for efficient chiral cyclopentadienyl ligands (Cp-x) has increased significantly in recent years, partly because Cp*Rh(III) species have been developed as powerful catalysts for directed C-H functionalization reactions. However, a lack of suitable Cp-x ligands has hampered the development of the corresponding enantioselective processes. We report expansions of the libraries of two generations of Cp-x ligands and their corresponding rhodium(I) complexes. The potential of the rhodium complexes as catalysts was evaluated in enantioselective C-H functionalizations involving cyclizations across tethered aldehydes. The mild reaction conditions permit the syntheses of hydroxychromanes and phthalides in good yields and high enantioselectivities.

Rh-I, Ir-III ,and Co-III Complexes with Atropchiral Biaryl Cyclopentadienyl Ligands: Syntheses, Structures, and Catalytic Activities

Nicolai Cramer, Coralie Danielle Annick Duchemin, Gints Smits

Chiral cyclopentadienyl (Cp-x) group 9 metal complexes have become versatile catalysts for a variety of efficient enantioselective C-H functionalizations. Atropchiral binaphthyl-derived Cp-x ligands having tuning options at the 3,3'-positions present a robust choice of catalyst, giving high enantioselectivities and good reactivities. Herein, we report streamlined syntheses of binaphthyl backbone Cp-x ligands that feature new substituents at the 3,3'-positions: namely, trimethylsilyl, I, and Br. We introduce as well Cp-x ligands with a new atropchiral MeO-biphenyl backbone. All ligands are smoothly complexed with rhodium(I) salts. The (CpRhI)-Rh-x complexes obtained were systematically mapped by X-ray crystal analysis in order to collect steric parameters that might guide a rational selection of the chiral Cp-x ligand for enantioselective reactions. The catalytic performances of the complexes were evaluated by two Rh-III-catalyzed C-H functionalizations as benchmark transformations. In both cases, a simpler to access ligand provided superior reactivity and enantioselectivity. Additionally, related (CpCoIII)-Co-x and (CpIrIII)-Ir-x complexes equipped with the developed ligands were prepared and characterized.

AMER CHEMICAL SOC2019

Asymmetric Synthesis of Isoindolones by Chiral Cyclopentadienyl-Rhodium(III)-Catalyzed C-H Functionalizations

Nicolai Cramer, Baihua Ye

Directed Cp*Rh-III-catalyzed carbon-hydrogen (C-H) bond functionalizations have evolved as a powerful strategy for the construction of heterocycles. Despite their high value, the development of related asymmetric reactions is largely lagging behind due to a limited availability of robust and tunable chiral cyclopentadienyl ligands. Rhodium complexes comprising a chiral Cp ligand with an atropchiral biaryl backbone enables an asymmetric synthesis of isoindolones from arylhydroxamates and weakly alkyl donor/acceptor diazo derivatives as one-carbon component under mild conditions. The complex guides the substrates with a high double facial selectivity yielding the chiral isoindolones in good yields and excellent enantioselectivities.

Wiley-Blackwell2014

Chiral Cyclopentadienyls: Enabling Ligands for Asymmetric Rh(III)-Catalyzed C-H Functionalizations

Nicolai Cramer, Baihua Ye

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 C-2-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 (CpRh)-Rh-x(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 CH functionalization reactions. These Cp-x derivatives hold promise as powerful steering ligands for further transition-metals used in asymmetric catalysis.

American Chemical Society2015

Chiral Cyclopentadienyls: Enabling Ligands for Asymmetric Rh(III)-Catalyzed C-H Functionalizations

Nicolai Cramer, Baihua Ye

American Chemical Society2015