Catalytic performance of Noyori–Ikariya-type ruthenium complex with tethered syn-ULTAM ligand for the asymmetric transfer hydrogenation of ketones

The ruthenium complex of the tethered syn-ULTAM ligand, i.e. syn-3-(α-aminobenzyl)-benzo-γ-sultam, has been evaluated for the asymmetric transfer hydrogenation (ATH) of a variety of ketones in formic acid/triethylamine mixture. Its performance was similar to the established Noyori–Ikariya-type catalysts for the reduction of benzo-fused cyclic ketones, but the enantioselectivity for the reduction of acetophenone was only moderate. The syn-ULTAM-based catalyst was particularly efficient and enantioselective for ATH of the sterically demanding α,α-disubstituted ketones. Moreover, we report a divergent ATH of 2-phenyl-1,3-indandione to either cis-2-phenyl-1-indanol, or cis,trans-2-phenyl-1,3-indandiol

Pyridine wingtip in ▫[Pd(Py−tzNHC)2]2+[Pd(Py-tzNHC)_2]^{2+}▫ complex is a proton shuttle in the catalytic hydroamination of alkynes

The cationic palladium(II) complex 1 of pyridylmesoionic carbene ligand catalyzes Markovnikov-selective intermolecular hydroamination between anilines and terminal alkynes into the corresponding imines. The reaction proceeds at room temperature, in the absence of additives, with exquisite selectivity and diverse functional group tolerance. The key intrinsic feature of the catalyst is the pyridine wingtip confined to the proximity of the alkynophilic metal active site, which mimics the function of enzyme-like architectures by assisting entropically favored proton transfers

Stereoarrayed 2,3-Disubstituted 1‑Indanols via Ruthenium(II)-Catalyzed Dynamic Kinetic Resolution–Asymmetric Transfer Hydrogenation

Activated racemic 2,3-disubstituted 1-indanones <b>1</b> possessing two stereolabile centers were stereoselectively reduced to the corresponding chiral 2,3-disubstituted-1-indanols <b>2</b> by ruthenium­(II)-catalyzed dynamic kinetic resolution–asymmetric transfer hydrogenation. In particular, this route offers a practical access to a new class of conformationally rigid enantiopure 1,4-diols <b>2k</b>–<b>m</b> having four contiguous chiral centers. Transformation of <i>ent</i>-<b>2k</b> into a Pallidol analogue via a highly diastereo- and regioselective Friedel–Crafts benzylation of <i>o</i>-chloroanisole is presented

Hydrogen-bonding ability of Noyori–Ikariya catalysts enables stereoselective access to CF3_3-substituted syn-1,2-diols via dynamic kinetic resolution

Stereopure CF$_3$-substituted syn-1,2-diols were prepared via the reductive dynamic kinetic resolution of the corresponding racemic α-hydroxyketones in HCO$_2$H/Et$_3$N. (Het)aryl, benzyl, vinyl, and alkyl ketones are tolerated, delivering products with ≥95% ee and ≥87:13 syn/anti. This methodology offers rapid access to stereopure bioactive molecules. Furthermore, DFT calculations for three types of Noyori–Ikariya ruthenium catalysts were performed to show their general ability of directing stereoselectivity via the hydrogen bond acceptor SO$_2$ region and CH/π interactions

Homochiral β-CF3, -SCF3 and -OCF3 secondary alcohols: catalytic stereoconvergent synthesis, bioactivity and flexible crystals

An optimized catalytic protocol for enantio- and diastereoselective reduction of racemic α-CF3, α-SCF3 and α-OCF3 aryl ketones is described. The reaction involves a dynamic kinetic resolution (DKR) based on ruthenium catalyzed Noyori–Ikariya asymmetric transfer hydrogenation for simultaneous construction of two contiguous stereogenic centers. A range of previously inaccessible fluorinated secondary alcohols was prepared in excellent stereomeric purity (up to above 99.9% ee, up to above 99.9:0.1 dr) and in high isolated yield (up to 99%). The origin of DKR (exceptional stereoselectivity and racemization mechanism) is rationalized by density functional theory calculations. Pharmaceutically relevant further transformations of the products are demonstrated including incorporation into heat shock protein 90 inhibitor with in vitro anti-cancer activity. Moreover, needle-shaped crystals of representative stereopure products are mechanically responsive: either elastically or plastically flexible, opening the door to novel class of functional materials based on chiral molecular crystals

Catalytic Stereoconvergent Synthesis of Homochiral β-CF 3 , β-SCF 3 , and β-OCF 3 Benzylic Alcohols

International audienceWe describe an efficient catalytic strategy for enantio- and diastereoselective synthesis of homochiral β-CF3, β-SCF3, and β-OCF3 benzylic alcohols. The approach is based on dynamic kinetic resolution (DKR) with Noyori–Ikariya asymmetric transfer hydrogenation leading to simultaneous construction of two contiguous stereogenic centers with up to 99.9% ee, up to 99.9:0.1 dr, and up to 99% isolated yield. The origin of the stereoselectivity and racemization mechanism of DKR is rationalized by density functional theory calculations. Applicability of the previously inaccessible chiral fluorinated alcohols obtained by this method in two directions is further demonstrated: As building blocks for pharmaceuticals, illustrated by the synthesis of heat shock protein 90 inhibitor with in vitro anticancer activity, and in particular, needle-shaped crystals of representative stereopure products that exhibit either elastic or plastic flexibility, which opens the door to functional materials based on mechanically responsive chiral molecular crystals