Enantioselective Zinc‐Catalyzed Hydrosilylation of Ketones using Pybox or Pybim Ligands

The combination of ZnEt₂ and chiral pyridinebisoxazoline (pybox) or pyridinebisimidazoline (pybim) ligands catalyzed the asymmetric hydrosilylation of aryl, alkyl, cyclic, heterocyclic, and aliphatic ketones. Under mild conditions, high yields and good enantioselectivities were achieved. ESI measurements allowed for the characterization of the active catalyst.     

Design and Synthesis of Isocyanide Ligands for Catalysis: Application to Rh‐Catalyzed Hydrosilylation of Ketones

New isocyanide ligands with meta‐terphenyl backbones were synthesized. 2,6‐Bis[3,5‐bis(trimethylsilyl)phenyl]‐4‐methylphenyl isocyanide exhibited the highest rate acceleration in rhodium‐catalyzed hydrosilylation among other isocyanide and phosphine ligands tested in this study. ¹H NMR spectroscopic studies on the coordination behavior of the new ligands to [Rh(cod)₂]BF₄ indicated that 2,6‐bis[3,5‐bis(trimethylsilyl)phenyl]‐4‐methylphenyl isocyanide exclusively forms the biscoordinated rhodium–isocyanide complex, whereas less sterically demanding isocyanide ligands predominantly form tetracoordinated rhodium–isocyanide complexes. FTIR and ¹³C NMR spectroscopic studies on the hydrosilylation reaction mixture with the rhodium–isocyanide catalyst showed that the major catalytic species responsible for the hydrosilylation activity is the Rh complex coordinated with the isocyanide ligand. DFT calculations of model compounds revealed the higher affinity of isocyanides for rhodium relative to phosphines. The combined effect of high ligand affinity for the rhodium atom and the bulkiness of the ligand, which facilitates the formation of a catalytically active, monoisocyanide–rhodium species, is proposed to account for the catalytic efficiency of the rhodium–bulky isocyanide system in hydrosilylation.     

Iron‐ and Cobalt‐Catalyzed Asymmetric Hydrosilylation of Ketones and Enones with Bis(oxazolinylphenyl)amine Ligands

Chiral bis(oxazolinylphenyl)amines proved to be efficient auxiliary ligands for iron and cobalt catalysts with high activity for asymmetric hydrosilylation of ketones and asymmetric conjugate hydrosilylation of enones.     

Copper‐Catalyzed Asymmetric Conjugate Addition with Chiral SimplePhos Ligands

SimplePhos ligands represent a novel class of monodentate chiral ligands based on a chiral amine moiety and flexible diaryl groups on the phosphorous atom. They can be easily prepared by two different pathways and they can be highly functionalised. Herein we report the copper‐catalysed asymmetric conjugate addition of diethyl zinc and trialkylaluminium reagents with SimplePhos ligands, which gives high enantioselectivity with cyclic enones, acyclic enones and nitro‐olefins, with up to 98.6 % ee. Of particular interest is the reaction of trialkylaluminium reagents with a wide range of 3‐substituted enones, thus allowing the formation of stereogenic quaternary carbon centres.     

Asymmetric Hydrosilylation of Aromatic Ketones Catalyzed by an Economical and Effective Copper-Diphosphine Catalytic System in Air

In the presence of the inexpensive and non‐toxic polymethylhydrosiloxane, the combination of copper(II) acetate and a chiral diphosphine displayed high catalytic efficiency in the asymmetric hydrosilylation of a series of aromatic ketones in air atmosphere and at room temperature. (R)‐1‐Arylethanols were obtained with up to 99% yield and 93% enantiomeric excess. Meanwhile, the electron effect and steric hindrance of substituents on the aromatic ring had an interesting influence on both the yields and enantioselectivities. Furthermore, a possible mechanism was presented to explain the influence of some key factors on the reaction.     

Chemo‐ and Stereoselective Iron‐Catalyzed Hydrosilylation of Ketones

The reduction of ketones with polymethylhydrosiloxane (PMHS) gives the corresponding alcohols in good to excellent yield applying iron‐based catalyst systems. In the case of prochiral ketones, the use of Fe(OAc)₂/(S,S)‐Me‐DuPhos leads to high enantioselectivity up to 99 % ee. The reaction proceeds in the presence of several functional groups such as esters, halides as well as conjugated double bonds, with high chemoselectivity. The advantage of this protocol is that the reaction requires no activating agents or additives.     

Application of Copper(II)–Dipyridylphosphine Catalyst in the Asymmetric Hydrosilylation of Simple Ketones in Air

Ask a copper : A copper(II) salt/chiral dipyridylphosphine/PhSiH₃ system (see scheme) acts as a very effective and practical catalyst for the asymmetric reduction of heteroaromatic and other types of ketones in air with good‐to‐excellent enantioselectivities (up to 94 %), giving many chiral alcohols that are intermediates for physiologically active compounds. Remarkable temperature effects were observed for some heteroaromatic ketones.

     

CuII‐Catalyzed Asymmetric Hydrosilylation of Diaryl‐ and Aryl Heteroaryl Ketones: Application in the Enantioselective Synthesis of Orphenadrine and Neobenodine

With certain amounts of sodium tert‐butoxide and tert‐butanol as additives, catalytic amounts of an inexpensive and easy‐to‐handle copper source Cu(OAc)₂ ? H₂O, a commercially available and air‐stable non‐racemic dipyridylphosphine ligand, as well as the stoichiometric desirable hydride donor polymethylhydrosiloxane (PMHS), formed a versatile in situ catalyst system for the enantioselective reduction of a broad spectrum of prochiral diaryl and aryl heteroarylketones in air, in high yields and with good to excellent enantioselectivities (up to 96 %). In particular, the practical viability of this process was evinced by its successful applications in the asymmetric synthesis of optically enriched potent antihistaminic drugs orphenadrine and neobenodine.     

Metal Silylenes Generated by Double Silicon–Hydrogen Activation: Key Intermediates in the Rhodium‐Catalyzed Hydrosilylation of Ketones

Rhodium silylenes , which are generated by double Si–H activation at the metal, are involved in a low‐activation‐barrier mechanism of the hydrosilylation of ketones with R₂SiH₂. A DFT‐based study of reaction mechanisms accounts for the experimental observations, notably the rate enhancement for R₂SiH₂ over R₃SiH and an inverse kinetic isotope effect.

     

Synthesis of Novel Monodentate Phosphoramidites and Their Application in Iridium‐Catalyzed Asymmetric Hydrogenations

New monodentate H₈‐binaphthol based phosphoramidites 6 b–i have been prepared. Starting from (S)‐3,3′‐dibromo‐5,5′,6,6′,7,7′,8,8′‐octahydro‐1,1′‐binaphthyl‐2,2′‐diol 3 , a general protocol for the synthesis of ligands 6 is presented. A small ligand library bearing aryl substituents in the 3,3′‐position of the binaphthol core was synthesized and successfully tested in the iridium‐catalyzed asymmetric hydrogenation of 2‐amidocinnamates to obtain different α‐amino acid derivatives in up to 99 % ee.     

Facile and Efficient Reduction of Ketones in the Presence of Zinc Catalysts Modified by Phenol Ligands

In the present study, the zinc‐catalyzed hydrosilylation of various ketones to give their corresponding alcohols has been examined in detail. Diethyl zinc that can be modified by easily accessible phenol ligands allows the efficient reduction of various aryl and alkyl ketones. By using a practical in situ catalyst, excellent turnover frequencies up to 1000 h^?1 and a broad functional group tolerance were achieved.     

Traceless Rhodium‐Catalyzed Hydroacylation Using Alkyl Aldehydes: The Enantioselective Synthesis of β‐Aryl Ketones

A one‐pot three‐step sequence involving Rh‐catalyzed alkene hydroacylation, sulfide elimination and Rh‐catalyzed aryl boronic acid conjugate addition gave products of traceless chelation‐controlled hydroacylation employing alkyl aldehydes. The stereodefined β‐aryl ketones were obtained in good yields with excellent control of enantioselectivity. Good variation of all three reaction components is possible.     

Highly Regio‐ and Stereoselective Hydrosilylation of Alkynes Catalyzed by Tridentate Cobalt Complexes

Several cobalt complexes bearing tridentate (NNN) ligands were synthesized and served as precatalysts for alkyne hydrosilylation with Ph₂SiH₂. For terminal alkynes, the catalyst L2 b‐CoCl₂ was selected, and resulted in the corresponding α‐vinylsilanes with high (Markovnikov) regioselectivity and extensive functional‐group tolerance. For internal diaryl alkynes, the catalyst L2 c‐CoCl₂ exhibited the best activity, and afforded E‐selective vinylsilanes through syn‐addition in excellent yield under mild conditions.     

Dynamic Kinetic Resolution of Heterobiaryl Ketones by Zinc‐Catalyzed Asymmetric Hydrosilylation

A diastereo‐ and highly enantioselective dynamic kinetic resolution (DKR) of configurationally labile heterobiaryl ketones is described. The DKR proceeds by zinc‐catalyzed hydrosilylation of the carbonyl group, thus leading to secondary alcohols bearing axial and central chirality. The strategy relies on the labilization of the stereogenic axis that takes place thanks to a Lewis acid–base interaction between a nitrogen atom in the heterocycle and the ketone carbonyl group. The synthetic utility of the methodology is demonstrated through stereospecific transformations into either N,N‐ligands or appealing axially chiral, bifunctional thiourea organocatalysts.     

Construction of a Chiral Silicon Center by Rhodium‐Catalyzed Enantioselective Intramolecular Hydrosilylation

Rhodium‐catalyzed enantioselective desymmetrizing intramolecular hydrosilylation of symmetrically disubstituted hydrosilanes is described. The original axially chiral phenanthroline ligand (S)‐BinThro (Binol‐derived phenanthroline) was found to work as an effective chiral catalyst for this transformation. A chiral silicon stereogenic center is one of the chiral motifs gaining much attention in asymmetric syntheses and the present protocol provides cyclic five‐membered organosilanes incorporating chiral silicon centers with high enantioselectivities (up to 91 % ee). The putative active Rh^I catalyst takes the form of an N,N,O‐tridentate coordination complex, as determined by several complementary experiments.