Pd-Catalyzed C(sp)-C(sp) Suzuki Coupling and Synthesis of Lumacaftor Using Designed Monophosphine Ligands.

Novel monophosphine ligands and with a C-P ring were designed and synthesized for the efficient Pd-catalyzed C(sp)-C(sp) Suzuki coupling. With 0.5 mol % Pddba and 2 mol % , aryl halides coupled with alkylboronic acids to give the products in up to 99% yield.

Ten-year trajectory of coronary artery calcification and risk of cardiovascular outcomes: the Multi-Ethnic Study of Atherosclerosis.

Background: Whether and how coronary artery calcium (CAC) progress contributes to cardiovascular outcomes has not been fully elucidated. The aim of this study was to identify different patterns of CAC change and evaluate the associations with different cardiovascular outcomes.

Methods: Data from the Multi-Ethnic Study of Atherosclerosis study were analyzed.

Recent advances in asymmetric synthesis of chiral amides and peptides: racemization-free coupling reagents.

Over past decades, chiral amides and peptides have emerged as powerful and versatile compounds due to their various biological activities and interesting molecular architectures. Although some chiral condensation reagents have been applied successfully for their synthesis, the introduction of racemization-free methods of amino acid activation have shown lots of advantages in terms of their low cost and low toxicity. In this review, advancements in amide and peptide synthesis using racemization-free coupling reagents over the last 10 years are summarized.

Recent advances in stereoselective construction of fluorinated quaternary carbon centers from fluorinated compounds.

There are many fluorinated quaternary carbon structural units in pharmaceuticals and bioactive compounds. Organic chemists are interested in the stereoselective synthesis of fluorinated quaternary carbon structural units. Constructing a fluorinated quaternary carbon stereocenter can be achieved directly and efficiently by the asymmetric catalytic reaction of fluorinated compounds as substrates.

Highly Regio- and Enantioselective Cu/Pd Co-Catalyzed Allylic Alkylation of α-pyridyl-α-fluoroesters: Construction of Quaternary C-F Stereocenters.

New methods for preparation of chiral alkyl fluorides have been studied intensively in recent years due to the favorable physicochemical and biological properties of those structures. Herein, we describe the regio- and enantioselective allylic alkylation of α-pyridyl-α-fluoroesters with allyl acetates promoted by Cu/Pd synergistic catalysis, constructing the carbon- fluorine quaternary stereocenters. In this co-catalytic system, palladium catalyst mainly constructed the C-C bond, while chiral copper catalyst controlled the enantioselectivity.

Ni/AntPohs-Catalyzed Stereoselective Asymmetric Intramolecular Reductive Coupling of -1,6-Alkynones.

An efficient nickel-catalyzed stereoselective asymmetric intramolecular reductive coupling of -1,6-alkynones is reported. A P-chiral monophosphine ligand AntPhos was found to be a privileged catalyst for constructing versatile functionalized chiral pyrrolidine rings using triethylsilane as the reducing reagent. Concise synthesis of pyrrolidines with chiral tertiary allylic alcohols was achieved in high yields (99%), excellent stereoselectivity (>99:1 /), and enantioselectivity (>99:1 er) with very broad substrate scope.

Enantioselective formation of quaternary carbon stereocenters in natural product synthesis: a recent update.

Covering: 2013-2018 Natural products bearing quaternary carbon stereocenters have attracted tremendous interest from the synthetic community due to their diverse biological activities and fascinating molecular architectures. However, the construction of these molecules in an enantioselective fashion remains a long-standing challenge because of the lack of efficient asymmetric catalytic methods for installing these motifs. The rapid progress in the development of new-generation efficient chiral catalysts has opened the door for several asymmetric reactions, such as Michael addition, dearomative cyclization, polyene cyclization, α-arylation, cycloaddition, allylation, for the construction of quaternary carbon stereocenters in a highly enantioselective fashion.

Total Synthesis and Stereochemical Assignment of Delavatine A: Rh-Catalyzed Asymmetric Hydrogenation of Indene-Type Tetrasubstituted Olefins and Kinetic Resolution through Pd-Catalyzed Triflamide-Directed C-H Olefination.

Delavatine A (1) is a structurally unusual isoquinoline alkaloid isolated from Incarvillea delavayi. The first and gram-scale total synthesis of 1 was accomplished in 13 steps (the longest linear sequence) from commercially available starting materials. We exploited an isoquinoline construction strategy and developed two reactions, namely Rh-catalyzed asymmetric hydrogenation of indene-type tetrasubstituted olefins and kinetic resolution of β-alkyl phenylethylamine derivatives through Pd-catalyzed triflamide-directed C-H olefination.

Asymmetric Alkylation of Anthrones, Enantioselective Total Synthesis of (-)- and (+)-Viridicatumtoxins B and Analogues Thereof: Absolute Configuration and Potent Antibacterial Agents.

A phase transfer catalyzed asymmetric alkylation of anthrones with cyclic allylic bromides using quinidine- or quinine-derived catalysts is described. Utilizing mild basic conditions and as low as 0.5 mol % catalyst loading, and achieving up to >99:1 dr selectivity, this asymmetric reaction was successfully applied to produce enantioselectively (-)- and (+)-viridicatumtoxins B, and thus allowed assignment of the absolute configuration of this naturally occurring antibiotic.

Efficient syntheses of korupensamines A, B and michellamine B by asymmetric Suzuki-Miyaura coupling reactions.

Efficient asymmetric Suzuki-Miyaura coupling reactions are employed for the first time in total syntheses of chiral biaryl natural products korupensamine A and B in combination with an effective diastereoselective hydrogenation, allowing ultimately a concise and stereoselective synthesis of michellamine B. Chiral monophosphorus ligands L1-3 are effective for the syntheses of a series of functionalized chiral biaryls by asymmetric Suzuki-Miyaura coupling reactions in excellent yields and enantioselectivities (up to 99% ee). The presence of a polar-π interaction between the highly polarized BOP group and the extended π system of arylboronic acid coupling partner is believed to be important for the high enantioselectivity.

Highly regioselective isomerization-hydroaminomethylation of internal olefins catalyzed by Rh complex with Tetrabi-type phosphorus ligands.

A highly regioselective isomerization-hydroaminomethylation of internal olefins has been developed. A 95.3% amine selectivity and 36.

Highly regioselective hydroaminomethylation of terminal olefins to linear amines using Rh complexes with a Tetrabi phosphorus ligand.

A highly regioselective hydroaminomethylation of terminal olefins catalyzed by Rh complexes with 2, 2', 6, 6'-tetrakis ((diphenylphosphino)methyl)-1, 1'-biphenyl (Tetrabi) ligand has been developed. Up to 99 % amine selectivity, 168 linear/branched amine product ratio (n/i), and 97.4 % linear amine yield has been obtained at a substrate/rhodium precursor ratio (S/Rh) of 1000 with this methodology.