C-H oxidation has a long history and an ongoing presence in research at the forefront of chemistry and interrelated fields. As such, numerous highly useful articles and reviews have been written on this subject. Logically, these are generally written from the perspective of the scope and limitations of the reagents employed. This Minireview instead attempts to emphasize chemoselectivity imposed by the nature of the substrate. Consequently, many landmark discoveries in the field of C-H oxidation are not discussed, but hopefully the perspective taken herein will allow C-H oxidation reactions to be more readily incorporated into synthetic planning.

/pdf/if-c-h-bonds-could-talk-selective-c-h-bond-oxidation-3n1lbwrvjm.pdf

If C-H bonds could talk: selective C-H bond oxidation.

Intellectual curiosity has always been one of the major driving forces leading to new advances in chemistry. At the onset of the 20th century, the fact that biaryls could be optically active even if lacking asymmetrically substituted carbon atoms arose interest, hinting at a novel type of stereomerism. It took quite a while (and some bizarre explanations)1 until in 1922 Christie and Kenner2 first correctly recognized that the phenomenon was the consequence of a hindered rotation about the aryl-aryl single bondshence termed atropisomerism by Kuhn. Still, no particular attention was initially paid to this class of stereoisomers until enantiomerically pure biaryls, such as BINAP (1),3 were found to be excellent ligands in asymmetric catalysis and until the chiral biaryl unit was recognized as the decisive structural element of many natural products (Figure 1).4,5 With the modern screening techniques and the bioassayguided search for novel compounds, the number of isolated axially chiral natural biaryls is steadily increasing.4 This class of secondary metabolites is characterized by a broad structural diversity, reaching from relatively simple molecules like the C2-symmetric biphenyl 2, which solely contains the element of axial chirality,6 to more complex compounds, like, e.g., the dimeric naphthylisoquinoline alkaloids michellamine A [(P,P)-3] and its axial epimer (i.e., its atropodiastereomer), michellamine B [(P,M)-3],7,8 which possess even three biaryl axes, of which the two outer ones are stereogenic, while * To whom correspondence should be addressed. E-mail: bringmann@ chemie.uni-wuerzburg.de; breuning@chemie.uni-wuerzburg.de. † These authors contributed equally to this work. ‡ Present address: Institute of Organic Chemistry, RWTH Aachen, Landoltweg 1, 52074 Aachen, Germany. § Present address: Kekulé Institute of Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk Str. 1, 53121 Bonn, Germany. Gerhard Bringmann was born in 1951 and studied chemistry in Gie en and Münster, Germany. After his Ph.D. with Prof. B. Franck in 1978 and postdoctoral studies with Prof. Sir D. H. R. Barton in Gif-sur-Yvette (France), he passed his habilitation at the University of Münster in 1984. In 1986, he received offers for full professorships of Organic Chemistry at the Universities of Vienna and Würzburg, of which he accepted the latter in 1987. In 1998, he was offered the position of director at the Leibniz Institute of Plant Biochemistry in Halle, which he declined. His research interests focus on the field of analytical, synthetic, and computational natural product chemistry, i.e., on axially chiral biaryls. He received several prizes and awards, among them the Otto-Klung Award in chemistry (1988), the Prize for Good Teaching of the Free State of Bavaria (1999), the Adolf-Windaus Medal (2006), the Honorary Doctorate of the University of Kinshasa (2006), the Paul-J.-Scheuer Award (2007), and the Honorary Guest Professorship of Peking University (2008). Chem. Rev. 2011, 111, 563–639 563

Atroposelective total synthesis of axially chiral biaryl natural products.

Department of Chemistry, Tianjin University, Tianjin 300072, China; Department of Applied Chemistry, China Agricultural University, Beijing 100193, China; UMR 6014 CNRS, Laboratoire COBRA de l’IRCOF, Université et INSA de Rouen, Rue Tesniere, F-76130 Mont Saint Aignan, France; and Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Science, Shanghai 200032, China

Asymmetric construction of stereogenic carbon centers featuring a trifluoromethyl group from prochiral trifluoromethylated substrates.

How good is fluorine as a hydrogen bond acceptor

This article reviews current knowledge of the metabolism of drugs that contain fluorine. The strategic value of fluorine substitution in drug design is discussed in terms of chemical structure and basic concepts in drug metabolism and drug toxicity.

Metabolism of fluorine-containing drugs.

Efficient synthesis of optically pure α-(fluoroalkyl)-β-sulfinyl enamines has been achieved by aza-Wittig reaction of triphenyliminophosphoranes with the corresponding α-fluorinated-α‘-sulfinyl ketones. The title compounds 3,4 showed an overwhelming preference for the Z stereochemistry of the enamine form. Their general reactivity has been studied. The reaction with some electrophiles (i.e. benzyl chloroformate and benzyl and allyl bromide) occurs at the nitrogen atom providing the corresponding N,N-disubstituted enamines. Nucleophiles add smoothly to C-2:  heteroatom-centered nucleophiles like methanol, ammonia, and thiophenol afford gem-disubstituted derivatives under thermodynamic control, while a C-centered nucleophile like nitromethane adds in irreversible fashion. The hydride- and deuteride-promoted reduction of 3,4 to the N-Cbz-protected (14) and N-unprotected (15) α-fluorinated-α‘-sulfinyl amines has been studied. Hydride addition was stereoselective, while low stereoselection was obtained with th...

New Versatile Fluorinated Chiral Building Blocks: Synthesis and Reactivity of Optically Pure α-(Fluoroalkyl)-β-sulfinylenamines

The structure and stereochemistry of Stemphyltoxins I–IV (1)–(4), four epoxy derivatives of reduced perylenequinones isolated from the fungus Stemphylium botryosum var. Lactucum, have been elucidated, mainly on the basis of n.m.r. evidence. A further metabolite, stemphyperylenol (5), is a hexahydro-1,4,7,10-tetrahydroxyperylene-3,9-quinone, a structure which suggests an unusual head-to-tail biosynthetic coupling of two pentaketide units.

Secondary mould metabolites. Part 16. Stemphyltoxins, new reduced perylenequinone metabolites from Stemphylium botryosum var. Lactucum

https://air.unimi.it/bitstream/2434/7815/1/Cladosporium%20su%20phytochemistry.pdf

Secondary mould metabolites of Cladosporium tenuissimum, a hyperparasite of rust fungi.

By treatment with perfluoro-cis-2-n-butyl-3-n-propyloxaziridine 1a, 5β-steroids 2a-i (belonging to different classes, such as androstanes, cholestanes, pregnanes, and cholanic acids) have been hydroxylated in good yields and with complete site selectivity and stereoselectivity to corresponding 5β-hydroxy derivatives 3a-i independently from the presence of halide, ketone, carboxylic acid, and ester moieties on C-3, C-11, C-12, C-17, C-20, C-21, and C-24

Alberto Arnone

Papers

New Versatile Fluorinated Chiral Building Blocks: Synthesis and Reactivity of Optically Pure α-(Fluoroalkyl)-β-sulfinylenamines

Secondary mould metabolites. Part 16. Stemphyltoxins, new reduced perylenequinone metabolites from Stemphylium botryosum var. Lactucum

Secondary mould metabolites of Cladosporium tenuissimum, a hyperparasite of rust fungi.

Direct Oxyfunctionalization at Unactivated Sites. Synthesis of 5.beta.-Hydroxysteroids by Perfluorodialkyloxaziridines

Structures of melleolides B-D, three antibacterial sesquiterpenoids from Armillaria mellea