Transition-Metal-Catalyzed Directing Group Assisted (Hetero)aryl C-H Functionalization: Construction of C-C/C-Heteroatom Bonds.

Transition-metal-catalyzed C-H functionalization is one of the fascinating scientific fronts in organic synthesis for the formation of conjugated arenes and has emerged as a benchmark to revolutionize the synthetic enterprise since past decades. In this realm, chelation-guided functionalization of C-H bonds using an exogenous directing group has received considerable attention recently for the expedient regioselective construction of C-C and C-heteroatom bonds as an efficient and sustainable alternative. This article outlines our contribution towards a wide variety of transformations that have been achieved by the directed C-H functionalization through the fine tuning of catalytic systems.

The transition-metal-catalyzed stereoselective ring-expansion of vinylaziridines and vinyloxiranes.

The transition-metal-aided stereoselective construction of sp3-carbon-rich heterocyclic scaffolds using strained-ring systems has received considerable attention in recent years due to the prominent presence of these scaffolds in myriad natural products, bioactive molecules, and pharmaceutical components. In this area, the catalytic ring-enlargement of vinylaziridines and vinyloxiranes plays a predominant role when synthesizing high sp3-content biorelevant heterocyclic compounds. This article aims to portray recent advancements in the ring-expansion of vinylaziridines and vinyloxiranes for accessing densely functionalized stereoselective heterocycles that have been developed over the past five years, with an emphasis on the substrate scopes and mechanistic insights into the key methodologies, and it is arranged based on the transition metals used and the ring sizes of the heterocyclic scaffolds.

Regioselectivity of the trifluoroethanol-promoted intramolecular N-Boc-epoxide cyclization towards 1,3-oxazolidin-2-ones and 1,3-oxazinan-2-ones.

The intramolecular N-Boc-epoxide cyclization leading to the formation of 1,3-oxazolidin-2-one and 1,3-oxazinan-2-one derivatives has scarcely been reported in the literature. More specifically, the intramolecular cyclization of N-Boc aniline-tethered 2,3-disubstitued epoxides has never been disclosed. Herein, we demonstrate that this reaction could proceed in a diastereoselective fashion in refluxing trifluoroethanol, in the absence of any external promoter or catalyst. Substrates bearing an alkyl group at the C-3 position furnished 1,3-oxazolidin-2-ones in a completely regioselective fashion via 5-exo epoxide ring-opening cyclization, thereby paving the way to synthesize alkyl side chain-bearing analogs of the antidepressant drug toloxatone. On the other hand, replacing the alkyl group with an aryl group resulted in easily separable mixtures of 1,3-oxazolidin-2-ones and 1,3-oxazinan-2-ones, the former being obtained as the major products. Remarkably, a tetralin-bearing substrate underwent fully regioselective 6-endo ring closure to form the corresponding 1,3-oxazinan-2-one. Our present study on the intramolecular ring opening-cyclization of epoxides with a tethered N-Boc group is the most comprehensive to date and features broad substrate scope, mild transition metal-free conditions, excellent functional group tolerance, and scalability.

Rh-Catalyzed tandem C-C/C-N bond formation of quinoxalines with alkynes leading to heterocyclic ammonium salts.

An efficient Rh-catalyzed oxidative C-H activation/annulation of 2-arylquinoxalines with internal alkynes is described using Cu(OAc)2·H2O and AgBF4 to afford a diverse variety of substituted quarternary ammonium salts at room temperature. The mechanism of the protocol is established on the basis of isolation of the 5-membered rhodacycle intermediate and kinetic isotope studies. The mild reaction conditions, substrate scope and functional group diversity are the salient practical features.

Transition-Metal-Catalyzed Directed C-H Functionalization in/on Water.

Directing group assisted C-H bond functionalization using transition-metal-catalysis has emerged as a reliable synthetic tool for the construction of regioselective carbon-carbon/heteroatom bonds. Off late, "in/on water directed transition-metal-catalysis", though still underdeveloped, has appeared as one of the prominent themes in sustainable organic chemistry. This article covers the advancements, mechanistic insights and application of the sustainable directed C-H bond functionalization of (hetero)arenes in/on water in the presence of transition-metal-catalysis.

Cascade C-H Activation/Annulation of Sulfoxonium Ylides with Vinyl Cyclopropanes: Access to Cyclopropane-Fused α-Tetralones.

Rh-catalyzed weak and traceless directing-group-assisted cascade C-H activation and annulation of sulfoxonium ylides with vinyl cyclopropanes as a coupling partner have been accomplished to furnish functionalized cyclopropane-fused tetralones at moderate temperature. The C-C bond formation, cyclopropanation, functional group tolerance, late-stage diversifications of drug molecules, and scale-up are the important practical features.

Pd-Catalyzed sp3 C-H alkoxycarbonylation of 8-methylquinolines using Mo(CO)6 as a CO surrogate.

A Pd(ii)-catalyzed three-component sp3 C-H alkoxycarbonylation of 8-methylquinonlines (8-MQs) with alcohols is accomplished using the colorless crystalline Mo(CO)6 as a CO source. The protocol is compatible with a wide range of 8-MQs and alcohols, furnishing the carbonylated adducts in moderate to good yields. The substrate scope, functional group tolerance and natural product mutation are the important practical features.

Pd-catalyzed bidentate auxiliary assisted remote C(sp3)-H functionalization.

Pd-catalyzed C-H functionalisation affords effective synthetic tools to construct C-C and C-X bonds. Despite the challenges, the distal functionalization of C(sp3)-H bonds has witnessed significant developments and the use of bidentate auxiliaries has garnished this area by providing an opportunity to control reactivity as well as selectivity beyond proximal sites. This article covers the recent developments on the Pd-catalyzed bidentate auxiliary-assisted distal C(sp3)-H functionalization and is categorized based on the nature of functionalizations.

Expedient iron-catalyzed stereospecific synthesis of triazines via cycloaddition of aziridines with diaziridines.

Iron-catalyzed stereospecific [3+3]-annulation of aziridines with diaziridines is described to furnish [1,2,4]-triazines in high yield at room temperature. The use of an inexpensive iron salt catalyst, substrate scope and enantiomeric purity are the important practical features.

Recent Advances in Stereoselective Ring Expansion of Spirocyclopropanes: Access to the Spirocyclic Compounds.

Spirocyclopropane represents a privileged structural scaffold for accessing synthetic libraries of densely functionalized spirocarbo- and heterocyclic compounds. Due to the ubiquity of spirocyclic motifs as a potent pharmacophore in natural products and pharmaceuticals, recent years have witnessed significant advances in developing synthetic strategies that exploits carbon-carbon bond scission in spirocyclopropanes. This paper summarizes the recent developments in stereoselective ring expansion of spirocyclopropanes in diversity-oriented synthesis and highlights the synthetic as well as mechanistic rationale of those methodologies. This review also encompasses the applicability of the protocols in bioactive natural product syntheses.