On Ying Yuen

A decade advancement of transition metal-catalyzed borylation of aryl halides and sulfonates

This review describes the recent advancement of transition metal-catalyzed aromatic carbon-boron bond construction processes. The efficacy of palladium, nickel and copper catalysis are comparatively illustrated. Particular focus is placed on the application of ligands, for instance tailor-made phosphines and carbenes that can effectively enable the borylation of challenging and sterically demanding substrates. Selected applications of this methodology for the synthesis of pharmaceutically useful and materially interesting molecules are mostly documented. This review includes literatures up to late 2012.

Synthesis of 3‑Cyanoindole Derivatives Mediated by Copper(I) Iodide Using Benzyl Cyanide

Copper-mediated direct and regioselective C3-cyanation of indoles using benzyl cyanide as the cyanide anion source is presented. A wide range of indoles undergo cyanation smoothly by employing a reaction system of copper(I) iodide under open-to-air vessels.

Carbon–Boron Bond Cross-Coupling Reaction Catalyzed by −PPh2 Containing Palladium–Indolylphosphine Complexes

This study describes the application of indolylphosphine ligands with a diphenylphosphino moiety to the palladium-catalyzed borylation of aryl chlorides. The combination of palladium metal precursor with PPh(2)-Andole-phos, which comprises an inexpensive -PPh(2) group, provides highly effective catalysts for the borylation of aryl chlorides. A range of functional groups such as -CN, -NO(2), -CHO, -COMe, -COOMe, and -CF(3) was compatible, and the catalyst loading down to 0.025 mol % of Pd can be achieved. The Pd/PPh(2)-Andole-phos system is able to catalyze both borylation reaction and Suzuki-Miyaura coupling reaction in a one-pot sequential manner for the direct synthesis of biaryl compounds in excellent yields.

Design of an Indolylphosphine Ligand for Reductive Elimination-Demanding Monoarylation of Acetone Using Aryl Chlorides

The rational design of a phosphine ligand for the reductive elimination-demanding Pd-catalyzed mono-α-arylation of acetone is demonstrated and reported. The catalyst is tolerant of previously proven challenging electron-deficient aryl chlorides and provides excellent product yields with down to 0.1 mol % Pd. Preliminary investigations suggest that the rate-limiting step for the proposed system is the oxidative addition of aryl chlorides, in which it contradicts previous findings regarding the α-arylation of acetone with aryl halides.

Exploiting Aryl Mesylates and Tosylates in Catalytic Mono-α-arylation of Aryl- and Heteroarylketones.

The first general palladium catalyst for the catalytic mono-α-arylation of aryl- and heteroarylketones with aryl mesylates and tosylates is described. The newly developed indolyl-derived phosphine ligand L7 has been identified to promote this reaction efficiently. The key to success is attributed to the enhanced steric congestion of the catalyst and effective oxidative addition of the C(Ar)-OMs bond. In the presence of Pd(OAc)2 (0.25-2.5 mol %) and L7, selective monoarylations are achieved with ample reaction scope and product yields up to 95%. Importantly, we demonstrated the applicability of this protocol with the modification of biological phenolic compounds, rendering it amenable for functionalization of phenolic (pro)drugs.

A General Direct Arylation of Polyfluoroarenes with Heteroaryl and Aryl Chlorides Catalyzed by Palladium Indolylphosphine Complexes

The first general examples of direct coupling of heteroaryl chlorides, especially substituted 2-pyridyl chlorides which were previously found to be problematic, with electron-deficient polyfluoroarenes are reported. Pd(OAc)2 associated with 3-(dicyclohexylphosphino)-2-phenylindole L1 serves as the effective catalyst which allows the challenging direct coupling of heteroaryl chlorides and polyfluoroarenes. In addition to heterocycles, a wide range of non-activated and activated aryl chlorides and alkenyl chlorides were also applicable under this catalyst system. A catalyst loading down to 1 mol % Pd can be achieved.

A General Palladium‐Catalyzed Hiyama Cross‐Coupling Reaction of Aryl and Heteroaryl Chlorides

A general palladium-catalyzed Hiyama cross-coupling reaction of aryl and heteroaryl chlorides with aryl and heteroaryl trialkoxysilanes by a Pd(OAc)2 /L2 catalytic system is presented. A newly developed water addition protocol can dramatically improve the product yields. The conjugation of the Pd/L2 system and the water addition protocol can efficiently catalyze a broad range of electron-rich, -neutral, -deficient, and sterically hindered aryl chlorides and heteroaryl chlorides with excellent yields within three hours and the catalyst loading can be down to 0.05 mol % Pd for the first time. Hiyama coupling of heteroaryl chlorides with heteroaryl silanes is also reported for the first time. The reaction can be easily scaled up 200 times (100 mmol) without any degasification and purification of reactants; this facilitates the practical application in routine synthesis.

Open-air oxidative Mizoroki–Heck reaction of arylsulfonyl hydrazides with alkenes

A palladium(II)-catalyzed oxidative Mizoroki–Heck reaction of arylsulfonyl hydrazides with alkenes was developed employing atmospheric air as the sole oxidant in an open-vessel manner. By using palladium(II) acetate associating with inexpensive, air-stable and moisture stable pyridine ligand L9 as the catalyst system, the efficiency of the reaction could be significantly enhanced. A wide range of arylsulfonyl hydrazides underwent the oxidative Mizoroki–Heck reaction with alkenes smoothly. Good-to-excellent product yields and excellent regio- and stereoselectivity were achieved. Functional groups such as halo, ester etc. were well-tolerated under these optimized reaction conditions.

Preparation of 2-(2-(Dicyclohexylphosphino)phenyl)-1-methyl-1H-indole (CM-phos)

A. 2-(2-Bromophenyl)-1H-indole. An oven-dried 100-mL single-necked round-bottomed flask equipped with a Teflon-coated magnetic stir bar (oval, 25 mm × 15 mm) is charged with 2-bromoacetophenone (2.7 mL, 4.0 g, 20 mmol) (Note 1) and phenylhydrazine (2.4 mL, 2.6 g, 24 mmol) (Note 2) via syringe, and stirring is started. Phosphoric acid (10.0 mL) (Note 3) is added slowly over 1 min, and the mixture is stirred for 50 min (Note 4). NHNH2 H3C O Br H3PO4, PPA N H Br +