Majji Shankar

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.

Ruthenium-Catalyzed ortho-C–H Mono- and Di-imidation of Arenes with N-Tosyloxyphthalimide

The Ru(II)-catalyzed imidation of the o-C-H bond in arenes with N-tosyloxyphthalimide is realized with the assistance of a methyl phenylsulfoximine (MPS) directing group. This method is applicable to access the hitherto difficult o-C-H di-imidation products. The sequential C-N and C-C bond formation of o-C-H arenes creates peripherally decorated benzoic acid derivatives. The readily removable MPS-DG and easily modifiable phthaloyl moiety make this strategy synthetically viable for constructing highly functionalized C-N bearing arenes and heteroarenes.

Silver-mediated oxidative annulation of N-arylthio succinimides with alkynes: direct access to benzo[b]thiophenes

A convenient synthetic route to 2,3-diarylbenzo[b]thiophene derivatives via Ag-catalyzed intermolecular oxidative cyclization between bench-stable N-arylthio succinimides and unactivated internal alkynes is demonstrated herein. The reaction indicates a broad scope, facilitating the construction of diverse arrays of π-conjugated 2,3-diaryl substituted benzothiophenes. The method involves oxidative cleavage of the S–N bond and annulation of alkynes with the concurrent 1,2-S-migration to yield benzo[b]thiophenes.

Transformable Sulfoximine Assisted One-Pot Double Annulation of Vinylic C–H Bonds with Unactivated Alkynes

The methylphenyl sulfoximine (MPS) directing group (DG) successfully promotes the one-pot double annulation of acrylic acids with alkynes under Ru catalysis, which is unprecedented. Diverse arrays of pyrido-fused-isoquinolinone skeletons are fabricated from acrylamides, creating two C-C and two C-N bonds in a single operation. The unsymmetrical annulation with two distinct alkynes is presented. The recovery of methylphenyl sulfoxide, a precursor of MPS, validates the synthetic adaptability of transformable-DG (TfDG) in C-H activation.

An Orchestrated Unsymmetrical Annulation Episode of C(sp2)–H Bonds with Alkynes and Quinones: Access to Spiro-isoquinolones

A nontrivial Ru-catalyzed one-pot sequential oxidative coupling of a (hetero)arene/vinylic/chromene system with alkyne and quinone is presented; the methyl phenyl sulfoximine (MPS) directing group is vital. This cyclization forms four (two C-C and two C-N) bonds in a single operation and produces unusual spiro-fused-isoquinolones with a broad scope. The release of phenyl methyl sulfoxide makes the MPS group transformable. A deuterium scrambling study sheds light on the reaction path.

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.