Compounds having cyclic molecular frameworks are highly regarded for their abundance and diverse utilities. In particular, medium-sized carbocycles and heterocycles exist in a broad spectrum of natural products, bioactive therapeutics, and medicinally significant synthetic molecules. Metal-mediated methods have been developed for the preparation of compounds containing a medium-sized ring (MSR) through cyclization of different classes of substrates and acyclic precursors. This review focuses on the methodologies for construction of MSRs via gold catalysis. Given the challenges in enabling the assembly of different ring sizes, we present here accounts on Au-mediated cyclization giving notable 7-membered and medium-sized (8–11-membered ring) structures. Emphasis on the pathway and mode of cyclization and the selection of precursors ranging from structurally biased compounds were outlined. Reactivity patterns and the choice of efficient Au catalysts for controlling reaction performance and selectivity in addition to mechanistic attributes are examined.

Herein, we show the highly enantioselective borylation of unactivated methylene C(sp3)–H bonds in 2-alkylpyridines and 2-alkyl-1,3-azole derivatives using an iridium-BINOL-based chiral monophosphite catalyst system. Quantum chemical calculations using the artificial force induced reaction (AFIR) method suggested that a monophosphite-Ir-tris(boryl) complex generates a narrow chiral reaction pocket where the differentiation of the enantiotopic methylene C–H bonds is accomplished through an assembly of multiple noncovalent interactions.

Site selectivity and stereocontrol remain major challenges in C–H bond functionalization chemistry, especially in linear aliphatic saturated hydrocarbon scaffolds. We report the highly enantioselective and site-selective catalytic borylation of remote C(sp3)–H bonds γ to the carbonyl group in aliphatic secondary and tertiary amides and esters. A chiral C–H activation catalyst was modularly assembled from an iridium center, a chiral monophosphite ligand, an achiral urea-pyridine receptor ligand, and pinacolatoboryl groups. Quantum chemical calculations support an enzyme-like structural cavity formed by the catalyst components, which bind the substrate through multiple noncovalent interactions. Versatile synthetic utility of the enantioenriched γ-borylcarboxylic acid derivatives was demonstrated.

α-Aminoboronic acids, isostructural boron analogues of α-amino acids, have received much attention because of the important biomedical applications implicated for compounds containing this structure. Additionally, the inherent versatility of α-aminoboronic acids as synthetic intermediates through diverse carbon−boron bond transformations makes the efficient synthesis of these compounds highly desirable. Here, we present a Rh-monophosphite chiral catalytic system that enables a highly efficient enantioselective borylation of N-adjacent C(sp 3 )−H bonds for a range of substrate classes including 2-(N-alkylamino)heteroaryls and Nalkanoyl-or aroyl-based secondary or tertiary amides, some of which are pharmaceutical agents or related compounds. Various stereospecific transformations of the enantioenriched α-aminoboronates, including Suzuki−Miyaura coupling with aryl halides and the Rh-catalyzed reaction with an isocyanate derivative of α-amino acid, affording a new peptide chain elongation method, have been demonstrated. As a highlight of this work, the borylation protocol was successfully applied to the catalyst-controlled site-selective and stereoselective C(sp 3 )−H borylation of an unprotected dipeptidic compound, allowing remarkably streamlined synthesis of the anti-cancer drug molecule bortezomib and offering a straightforward route for the synthesis of privileged molecular architectures.

Enantioselective heteroatom-directed C(sp 3 )H borylation reactions of 2-aminopyridines and 2-alkylpyridines with Rh-and Ir catalytic systems using commercially available chiral monophosphine ligands, respectively, were developed. This methodology provides an innovative example of a homogeneous catalytic system for C(sp 3 )H borylation, and allows the direct synthesis of optically active alkylboronates with a moderate level of enantioselectivity. Keywords: C-H activation | Borylation | Asymmetric catalysisThe synthesis of highly functionalized molecules via the direct and selective transformation of CH bonds is a highly attractive strategy and a fundamental frontier in organic synthesis. CH bond activation strategies in transition metal catalysis have become one of the most expedient and powerful tools in molecular diversification.1,2 While there has been significant progress in the direct transformation of C(sp 2 )H bonds, the functionalization of C(sp 3 )H bonds remains challenging due to both the absence of π-orbitals that can interact with a transition metal and the sterically demanding geometry of C(sp 3 )H bonds compared to planar C(sp 2 )H bonds. Moreover, enantioselective C(sp 3 )H functionalization contributing to an efficient access to optically active molecules is underdeveloped. Recently, our group reported the heteroatom-directed borylation of C(sp 3 )H bonds with heterogeneous Rh-and Ircatalyst systems based on silica-supported bridgehead monophosphines, Silica-SMAP and Silica-TRIP. 46 This strategy allowed site-selective borylation of the N-adjacent or unactivated C(sp 3 )H bonds located γ to N or O atoms in the directing groups due to the proximity effects by the heteroatom-to-metal coordination. We next turned our attention to develop their enantioselective versions to give optically active alkylboronates.7 Along this line, however, the structural modification of the silica-supported caged phosphines aiming to the asymmetric reactions would be challenging. On the basis of our knowledge that the controlled mono-P-ligation toward metals is crucial, 8 we thought to use appropriate soluble ligands to realize the heteroatom-directed C(sp 3 )H borylation. 9 This protocol can open a synthetic opportunity to explore and extend the borylation reactions under homogeneous catalysis. 10Herein, we report the Rh-or Ir-catalyzed site-selective C(sp 3 )H borylation of 2-aminopyridines and 2-alkylpyridines providing an innovative example of a homogeneous catalytic system. The use of a readily available chiral phosphoramidite as a ligand allows the direct synthesis of optically active alkylboronates with moderate level of enantioselectivity.Initially, to investigate the possibility of catalytic borylation using homogeneous ligands, our studies commenced by using 2-(pyrrolidine-1-yl)pyridine (1a) as the substrate towards Rhcatalyzed N-adjacent C(sp 3 )H borylation using bis(pinacolato)-diboron (2, 1.25 equiv) (Scheme 1). The reaction was conducted in CPME at 60°C over 15 h in the presence of [Rh(OH)(cod)] 2 (2 mo...