Raja K. Rit

Sulfoximine Directed Intermolecular o-C–H Amidation of Arenes with Sulfonyl Azides

The Ru(II)-catalyzed intermolecular o-C-H amidation of arenes in N-benzoylated sulfoximine with sulfonyl azides is demonstrated. The reaction proceeds with broad substrate scope and tolerates various functional groups. Base hydrolysis of the amidation product provides the anthranilic acid derivatives and methylphenyl sulfoximine (MPS) directing group. This method is successfully employed for the synthesis of HMR 1766.

Sulfoximines: A Reusable Directing Group for Chemo‐ and Regioselective ortho CH Oxidation of Arenes

Sulfoximines direct: a new protocol for the chemo- and regioselective ortho C-H acetoxylation of arenes in N-benzoylated sulfoximines is reported. The sulfoximine directing group is easily detached from the C-H oxidation product through acid-promoted hydrolysis, isolated, and reused. The meta-substituted phenols are synthesized following this strategy and the stereointegrity of the sulfoximine is preserved in this transformation. C(sp(3))-H acetoxylation of the methyl group is also demonstrated.

Ru(II)-catalyzed intermolecular ortho-C–H amidation of aromatic ketones with sulfonyl azides

Ru(II)-catalyzed intermolecular ortho-C-H amidation of weakly coordinating aromatic ketones with sulfonyl azides is reported. The developed reaction protocol can be extended to various substituted aromatic ketones to afford a wide range of desired C-N bond formation products in good yields.

Sulfoximine Assisted Pd(II)-Catalyzed Bromination and Chlorination of Primary β-C(sp3)–H Bond

S-methyl-S-2-pyridyl-sulfoximine (MPyS) directed bromination and chlorination of the 1°-β-C(sp(3))-H bond of MPyS-N-amides is realized under the influence of N-Br/Cl-phthalimides and a Pd(II)-catalyst. The sequential halogenation and acetoxylation of α-dimethyl MPyS-N-amides constructs highly functionalized α-trisubstituted aliphatic acid derivatives. The MPyS directing group is cleaved from the halogenated products and recovered.

Sulfoximine-directed ruthenium-catalyzed ortho-C-H alkenylation of (hetero)arenes: synthesis of EP3 receptor antagonist analogue.

The reusable sulfoximine directing-group-assisted Ru(II)-catalyzed chemo- and regioselective ortho-C-H alkenylation of arenes and heteroarenes with acrylates and α,β-unsaturated ketones/vinyl sulfone is shown. The N-aroyl sulfoximine undergoes annulation with diphenylacetylene, delivering isoquinolinones and methyl phenyl sulfoxide. The present protocol is successfully employed for the synthesis of the EP3 receptor antagonist analogue.

Pd(II)-Catalyzed ortho-C–H Oxidation of Arylacetic Acid Derivatives: Synthesis of Benzofuranones

Pd(II)-catalyzed ortho-C-H acetoxylation of arylacetic acid derivatives is demonstrated with the aid of a novel S-methyl-S-2-pyridylsulfoximine (MPyS) directing group (DG). The α-mono- and α-unsubstituted arylacetic acid derivatives were readily employed in the ortho-C-H acetoxylations. The oxidation products are hydrolyzed, and the MPyS-DG is easily recovered, providing ready access to o-hydroxyarylacetic acids. 3-Mono- and 3-unsubstituted benzofuranones are synthesized from o-hydroxyarylacetic acids.

Ruthenium-Catalyzed Hydroarylation and One-Pot Twofold Unsymmetrical C-H Functionalization of Arenes.

A methyl phenyl sulfoximine (MPS) is used as a directing group in the ruthenium-catalyzed intramolecular hydroarylation of alkene-tethered benzoic acid derivatives to afford dihydrobenzofurans and indolines in good to excellent yields. A one-pot, unsymmetrical, twofold C-H functionalization involving intramolecular C-C and intermolecular C-C/C-N bond formations is successfully demonstrated by using a single set of catalytic reaction conditions, which is unprecedented thus far. A novel isoquinolone-bearing dihydrobenzofuran is constructed through an unsymmetrical twofold C-H functionalization.

Ruthenium-Catalyzed Intramolecular Hydroarylation of Arenes and Mechanistic Study: Synthesis of Dihydrobenzofurans, Indolines, and Chromans

A ruthenium-catalyzed, amide-directed intramolecular hydroarylation of alkene-tethered benzamide derivatives is discussed. This method proficiently constructs dihydrobenzofuran, indoline, and chroman skeletons of biological significance in good to excellent yields; the overall process is atom-economical and step-efficient. The reaction exhibits broad scope, tolerating common functional groups, labile protecting units, and heteroaryl motifs. The use of a catalytic amount of base suffices the need. Deuterium scrambling and kinetic studies offer valuable facts for understanding the reaction mechanism.

One-Pot Unsymmetrical {[4 + 2] and [4 + 2]} Double Annulations of o/o′-C–H Bonds of Arenes: Access to Unusual Pyranoisoquinolines

With the aid of a transformable sulfoximine directing group, unprecedented one-pot unsymmetrical double annulations {[4 + 2] and [4 + 2]} of hetero(arenes) with alkynes are revealed under Ru(II) catalysis. Functionalization of both ortho-C-H bonds of (hetero)arene is reflected in the building of unusual 6,6-fused pyranoisoquinoline skeletons. Construction of four [(C-C)-(C-N) and (C-C)-(C-O)] bonds occurs in one step under single catalytic conditions. The challenging unsymmetrical double annulations of both o-C-H bonds of arenes with two distinct alkynes is effectively demonstrated. Control experiments and deuterium scrambling findings are shown.

Sulfoximine-Assisted One-Pot Unsymmetrical Multiple Annulation of Arenes: A Combined Experimental and Computational Study

Discussed herein is an unprecedented Ru-catalyzed one-pot unsymmetrical C-H difunctionalization of arenes comprising intramolecular hydroarylation of olefins and intermolecular annulation of alkynes. This unprecedented 2-fold C-H functionalization is validated on the basis of experimental and density functional theory (DFT) study. The transformation readily occurs with the assistance of methylphenyl sulfoximine (MPS) directing group in the presence of Ru catalyst forming two C-C and one C-N bonds in a single operation. The overall process is atom economical and step-efficient and provides unusual dihydrofuran-fused isoquinolone heterocycles. Further annulation of NH and the proximal o-C-H-arene of isoquinolone with alkynes build highly conjugated novel polycyclic compounds. Overall, three independent annulations in arene motifs are visualized and thoughtfully executed; finally, 5 ring-fused structural entities are constructed forming three C-C and two C-N bonds.