Qing-Hai Deng

Highly Enantioselective Copper-Catalyzed Electrophilic Trifluoromethylation of β-Ketoesters

Enantioselective Cu-catalyzed trifluoromethylation of β-ketoesters using commercially available trifluoromethylating reagents is reported. A number of α-CF(3) β-ketoesters are obtained with up to 99% ee. The trifluoromethylated products were then transformed diastereoselectively to α-CF(3) β-hydroxyesters with two adjacent quaternary stereocenters via a Grignard reaction.

Enantioselective Iron-Catalyzed Azidation of β-Keto Esters and Oxindoles

The first example of Fe-catalyzed enantioselective azidations of β-keto esters and oxindoles using a readily available N3-transfer reagent is reported. A number of α-azido-β-keto esters were obtained with up to 93% ee, and this methodology also generates 3-substitued 3-azidooxindoles with high enantioselectivities (up to 94%).

Copper-boxmi complexes as highly enantioselective catalysts for electrophilic trifluoromethylthiolations.

The enantioselective trifluoromethylthiolation of β-ketoesters using chiral copper-boxmi complexes as catalysts is reported. A number of α-SCF3-substituted β-ketoesters have been obtained with up to >99% enantiomeric excess (ee), and the trifluoromethylthiolated products were then transformed diastereoselectively to α-SCF3-β-hydroxyesters with two adjacent quaternary stereocenters.

The Synthesis of a New Class of Chiral Pincer Ligands and Their Applications in Enantioselective Catalytic Fluorinations and the Nozaki–Hiyama–Kishi Reaction

A new class of chiral tridentate N-donor pincer ligands, bis(oxazolinylmethylidene)isoindolines (boxmi), was synthesized in three steps starting from readily available phthalimides. Their reaction with ethyl (triphenylphosphoranylidene)acetate by means of a key-step Wittig reaction gave the ligand backbones, which were condensed with amino alcohols and then cyclized to obtain the corresponding ligands. These ligands were subsequently applied in the nickel(II)-catalyzed enantioselective fluorination of oxindoles and β-ketoesters to obtain the corresponding products with enantioselectivities of up to >99% ee and high yields. Application of the chiral pincer ligands in the chromium-catalyzed enantioselective Nozaki-Hiyama-Kishi reaction of aldehydes gave the corresponding alcohols with an optimal enantioselectivity of 93%.

Highly selective metal catalysts for intermolecular carbenoid insertion into primary C-H bonds and enantioselective C-C bond formation.

Direct functionalization of C H bonds is an appealing strategy in organic synthesis but its practical application has so far been difficult to realize. The selective functionalization of primary C H bonds of alkanes that also contain secondary and/or tertiary C H bonds is a great challenge, as C H bond energy follows an order primary> secondary> tertiary. In seminal works by Bergman, Jones, and their respective co-workers, stoichiometric reactions of alkanes with [Cp*(Me3P)M] (Cp* = C5Me5; M = Rh, Ir) resulted in the formation of C M bonds by selective activation of primary C H bonds. Subsequent work by Hartwig and coworkers 2] demonstrated C B bond formation by stoichiometric and catalytic functionalization of primary C H bonds mediated by tungsten, rhodium, or ruthenium complexes. The high selectivity for primary C H bond functionalization in these C M or C B bond-formation reactions (Scheme S1 in the Supporting Information) is considered to result from kinetic factors or steric interaction between the metal complexes and alkanes. 3] A well-established process in C C bond formation by direct C H bond functionalization is the metal-catalyzed intraand intermolecular carbenoid insertion into C H bonds, with diazo compounds as the carbene source. 4] These catalytic C C bond-formation reactions generally feature lower selectivity for primary C H bonds than for secondary and tertiary C H bonds. For example, a selectivity order of primary< secondary< tertiary C H bonds has been observed for the extensively investigated carbene insertion catalyzed by rhodium complexes, 5] possibly because of the electron density order of primary< secondary< tertiary C H bonds, which renders primary C H bonds the least susceptible to attack by electrophilic rhodium–carbene intermediates. By manipulating the steric or electronic properties of the metal catalysts, a selectivity for primary C H bonds of alkanes comparable to that for secondary or tertiary C H bonds was observed, with the highest primary/secondary and primary/tertiary ratio per C H bond being 1.17:1.0 and 1.0:0.9, respectively. Herein we report a highly selective primary C H bond functionalization by metal-catalyzed carbenoid insertion into the C H bonds of alkanes (Scheme 1), which features a

Ruthenium-catalyzed one-pot carbenoid N-H insertion reactions and diastereoselective synthesis of prolines.

Aryl- and aliphatic-substituted 3-hydroxyprolines and various other amino esters are conveniently prepared by [RuCl2(p-cymene)]2-catalyzed one-pot intramolecular and intermolecular carbenoid N-H insertion reactions, respectively, and the prolines are formed with high diastereoselectivities. The catalytic reactions are tolerant toward air/moisture, and the product yields are insensitive to the organic solvents used.

Highly enantioselective intermolecular carbene insertion to C–H and Si–H bonds catalyzed by a chiral iridium(III) complex of a D4-symmetric Halterman porphyrin ligand

The chiral iridium porphyrin [Ir((-)-D(4)-Por*)(Me)(EtOH)] displays excellent reactivity and stereoselectivity towards carbene insertion to C-H and Si-H bonds, affording corresponding products in high yields (up to 96%) and high enantioselectivities (up to 98% ee).

Highly Enantioselective Copper-Catalyzed Alkylation of β-Ketoesters and Subsequent Cyclization to Spirolactones/Bi-spirolactones

Cu-catalyzed enantioselective alkylation of β-ketoesters using alcohols for in situ preparation of alkylating reagents is reported. A number of functionalized β-ketoesters containing a quaternary carbon stereocenter are obtained with up to 99% ee. The alkylation products derived from 2-substituted allylic alcohols or their corresponding iodides can then be converted to spirolactones, bi-spirolactones, and related chiral target products.

A Non‐Cross‐Linked Soluble Polystyrene‐Supported Ruthenium Catalyst for Carbenoid Transfer Reactions

Ruthenium nanoparticles supported on non-cross-linked soluble polystyrene were prepared by reacting [RuCl(2)(C(6)H(5)CO(2)Et)](2) with polystyrene in open air. They effectively catalyze intra- and intermolecular carbenoid insertion into C-H and N-H bonds, alkene cyclopropanation, and ammonium ylide/[2,3]-sigmatropic rearrangement reactions. This supported ruthenium catalyst is much more reactive than [RuCl(2)(p-cymene)](2) and [Ru(Por)CO] for catalytic intermolecular carbenoid C-H bond insertion into saturated alkanes. By using alpha-diazoacetamide as a substrate for intramolecular carbenoid C-H insertion, the supported ruthenium catalyst can be recovered and reused for ten successive iterations without significant loss of activity.

Radical Changes in Lewis Acid Catalysis: Matching Metal and Substrate

Whereas the stereochemical rigidity of the coordination sphere of boxmi/Cu(II) catalysts is key to achieving high enantioselectivity in the electrophilic alkylation of β-ketoesters, this pathway is outperformed by a radical process for the corresponding catalytic transformation of oxindoles, giving rise to racemic products. For the corresponding Zn(II) catalysts, the selectivity in the latter process is outstanding despite the greater plasticity of the coordination shell. This reaction was thus developed into a highly useful synthetic method, which enabled the conversion of wide range of substrates with high yields and enantioselectivities.