Regioselective Radical Arene Amination for the Concise Synthesis of <i>ortho</i>-Phenylenediamines.

The formation of arene C-N bonds directly from C-H bonds is of great importance and there has been rapid recent development of methods for achieving this through radical mechanisms, often involving reactive N-centered radicals. A major challenge associated with these advances is that of regiocontrol, with mixtures of regioisomeric products obtained in most protocols, limiting broader utility. We have designed a system that utilizes attractive noncovalent interactions between an anionic substrate and an incoming radical cation in order to guide the latter to the arene ortho position. The anionic substrate takes the form of a sulfamate-protected aniline and telescoped cleavage of the sulfamate group after amination leads directly to ortho-phenylenediamines, key building blocks for a range of medicinally relevant diazoles. Our method can deliver both free amines and monoalkyl amines allowing access to unsymmetrical, selectively monoalkylated benzimidazoles and benzotriazoles. As well as providing concise access to valuable ortho-phenylenediamines, this work demonstrates the potential for utilizing noncovalent interactions to control positional selectivity in radical reactions

Biocatalytic Conversion of Cyclic Ketones Bearing α-Quaternary Stereocenters into Lactones in an Enantioselective Radical Approach to Medium-Sized Carbocycles

Cyclic ketones bearing alpha-quaternary stereocenters undergo efficient kinetic resolution using cyclohexanone monooxygenase (CHMO) from Acinetobacter calcoaceticus. Lactones possessing tetrasubstituted stereocenters are obtained with high enantioselectivity (up to >99% ee) and complete chemoselectivity. Preparative scale biotransformations were exploited in conjunction with a SmI2-mediated cyclization process to access complex, enantiomerically enriched cycloheptan- and cycloctan-1,4-diols. In a parallel approach to structurally distinct products, enantioenriched ketones from the resolution bearing an alpha- all carbon quaternary stereocenter were used in a SmI2-mediated cyclization process to give cyclobutanol products (up to >99% ee)

An Aminative Rearrangement of O-(Arenesulfonyl)hydroxylamines: Facile Access to ortho-Sulfonyl Anilines.

Ortho-sulfonyl anilines are important building blocks for a range of applications. We report the discovery of an aromatic rearrangement reaction of O-(arenesulfonyl)hydroxylamines which leads directly to ortho-sulfonyl anilines through formation of a new C-N bond with excellent levels of regiocontrol for the ortho position(s) over all others. We establish that the rearrangement is proceeding through an intermolecular mechanism and propose that the regiocontrol observed is the result of attractive non-covalent interactions occurring during the C-N bond-forming step. Importantly, this method is complementary to classical aniline sulfonation in terms of the variously substituted regioisomers that can be obtained and it is also applicable to O-(benzylsulfonyl) hydroxylamines

CCDC 1450489: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

CCDC 1450488: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures

Diastereoselective radical 1,4-ester migration: radical cyclizations of acyclic esters with SmI2

[Image: see text] Reductive cyclizations of carbonyl compounds, mediated by samarium(II) diiodide (SmI(2), Kagan’s reagent), represent an invaluable platform to generate molecular complexity in a stereocontrolled manner. In addition to classical ketone and aldehyde substrates, recent advances in radical chemistry allow the cyclization of lactone and lactam-type substrates using SmI(2). In contrast, acyclic esters are considered to be unreactive to SmI(2) and their participation in reductive cyclizations is unprecedented. Here, we report a diastereoselective radical 1,4-ester migration process, mediated by SmI(2), that delivers stereodefined alkene hydrocarboxylation products via radical cyclization of acyclic ester groups in α-carbomethoxy δ-lactones. Isotopic labeling experiments and computational studies have been used to probe the mechanism of the migration. We propose that a switch in conformation redirects single electron transfer from SmI(2) to the acyclic ester group, rather than the “more reactive” lactone carbonyl. Our study paves the way for the use of elusive ketyl radicals, derived from acyclic esters, in SmI(2)-mediated reductive cyclizations

CCDC 1425808: Experimental Crystal Structure Determination

An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures