https://pubs.rsc.org/en/content/articlepdf/2019/NP/C8NP00092A

Marine natural products.

Compounds Currently in Phase II−III Clinical Trials of Major Pharmaceutical Companies: New Structural Trends and Therapeutic Areas Yu Zhou,† Jiang Wang,† Zhanni Gu,† Shuni Wang,† Wei Zhu,† Jose ́ Luis Aceña,*,‡,§ Vadim A. Soloshonok,*,‡,∥ Kunisuke Izawa,* and Hong Liu*,† †Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Shanghai 201203, China ‡Department of Organic Chemistry I, Faculty of Chemistry, University of the Basque Country UPV/EHU, Paseo Manuel Lardizab́al 3, 20018 San Sebastiań, Spain Department of Organic Chemistry, Autońoma University of Madrid, Cantoblanco, 28049 Madrid, Spain IKERBASQUE, Basque Foundation for Science, María Díaz de Haro 3, 48013 Bilbao, Spain Hamari Chemicals Ltd., 1-4-29 Kunijima, Higashi-Yodogawa-ku, Osaka, Japan 533-0024

Next Generation of Fluorine-Containing Pharmaceuticals, Compounds Currently in Phase II–III Clinical Trials of Major Pharmaceutical Companies: New Structural Trends and Therapeutic Areas

1,2-Amino Alcohols and Their Heterocyclic Derivatives as Chiral Auxiliaries in Asymmetric Synthesis

Dicarbonyl (η5-cyclopentadienyl)cobalt functions as a matrix on which a variety of unsaturated organic substrates undergo mutual bond formation. In this way α,ω-diynes cocyclize with monoalkynes to give annelated benzenes, while o-diethynylbenzenes furnish biphenylenes, and α,ω-enynes lead to the formation of complexed bi-and tricyclic dienes. Nitriles cocyclize with two alkynyl groups to give pyridines and other heterocycles, isocyanates allow access to annelated 2-pyridones, and incorporation of carbon monoxide provides complexed cyclopentadienones. In many cases remarkable chemo-, regio-, and stereoselectivity are observed, partially facilitated by use of the trimethylsilyl substituent as a controlling group. The scope and level of maturity of the method are demonstrated by the synthesis of a series of hitherto inaccessible, novel, and theoretically interesting molecules, and by its utilization in several unique approaches to a variety of natural products, e.g. protoberberines, steroids, vitamin B6, and camptothecin.

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Cobalt‐Mediated [2 + 2 + 2]‐Cycloadditions: A Maturing Synthetic Strategy [New Synthetic Methods (43)]

Monofluorination of Organic Compounds: 10 Years of Innovation.

Michael addition of the lithium amide derived from R-N-(α-methylbenzyl)benzylamine to benzyl E-crotonate is highly stereoselective (95% d.e.) giving after debenzylation and crystallisation homochiral R-β-amino butanoic acid. A similar addition to methyl E-(p-benzyloxy)cinnamate is completely stereoselective giving after debenzylation and acid hydrolysis homochiral S-β-tyrosine as its HCl salt.

Asymmetric synthesis of R-β-amino butanoic acid and S-β-tyrosine: Homochiral lithium amide equivalents for Michael additions to α,β-unsaturated esters.

Nucleophilic addition to organotransition metal cations containing unsaturated hydrocarbon ligands : A survey and interpretation

The Balz-Schiemann synthesis of aryl fluorides via the thermal decomposition of aryl diazonium tetrafluoroborate salts represents both the earliest and the most proverbial example of the BF4 ion as a nucleophilic fluoride source. Mechanistic studies of the Balz-Schiemann reaction have accrued strong experimental support for an SN1 mechanism via the intermediacy of an aryl cation, which is quenched by fluoride transfer directly from the BF4 ion. A notable advance in this area has been the development by Ohmori and co-workers of a fluorinative variant of the Mitsunobu reaction, involving the electrooxidative generation and subsequent thermal decomposition of alkoxytriphenylphosphonium tetrafluoroborates, allowing for the conversion of alcohols to the corresponding alkyl fluorides with inversion of configuration. Although stereoselectivity during C-F bond formation for reactions proceeding via (putative) carbocation intermediates can be highly variable, the ring-opening of strained rings or ?iranium intermediates via fluoride transfer from fluoroborate ions typically proceeds with high stereoselectivity.

Beyond the Balz-Schiemann reaction: the utility of tetrafluoroborates and boron trifluoride as nucleophilic fluoride sources.

An investigation into the reactivity of the highly stereoselective conjugate nucleophile lithium N-benzyl-N-α-methylbenzylamide 1 with α-alkyl-α,β-unsaturated esters has led to the development of a versatile asymmetric synthesis of syn-α-alkyl-β-amino acids. By performing the conjugate additions in toluene and diluting the reaction mixtures with THF prior to quenching of the reactions with the hindered acid, 2,6-di-tert-butylphenol 13, the product syn-α-alkyl-β-amino esters may be generated in good yield and with excellent stereocontrol. Several examples illustrate the ease with which these products may be debenzylated and hydrolysed to afford homochiral syn-α-alkyl-β-amino acids.

Asymmetric synthesis of syn-α-alkyl-β-amino acids

Treatment of a range of N-benzyl tertiary amines with aqueous ceric ammonium nitrate results in N-debenzylation to afford the corresponding secondary amine. Chemoselective mono-N-debenzylation of N-benzyl tertiary amines is shown to occur in the presence of N-benzyl amides, O-benzyl ethers, O-benzyl esters, O-benzyl phenolates and S-benzyl ethers.

Stephen G. Davies

Papers

Asymmetric synthesis of R-β-amino butanoic acid and S-β-tyrosine: Homochiral lithium amide equivalents for Michael additions to α,β-unsaturated esters.

Nucleophilic addition to organotransition metal cations containing unsaturated hydrocarbon ligands : A survey and interpretation

Beyond the Balz-Schiemann reaction: the utility of tetrafluoroborates and boron trifluoride as nucleophilic fluoride sources.

Asymmetric synthesis of syn-α-alkyl-β-amino acids

Chemoselective debenzylation of N-benzyl tertiary amines with ceric ammonium nitrate