Soichiro Kawamorita

Directed Ortho Borylation of Functionalized Arenes Catalyzed by a Silica-Supported Compact Phosphine−Iridium System

An immobilized monophosphine-Ir system, which was prepared in situ from [Ir(OMe)(cod)](2) and a silica-supported, compact phosphine, showed high activities and selectivities for the borylation of aromatic C-H bonds with bis(pinacolato)diboron. This system was effective not only for the borylation of benzene but also for the ortho borylation of arenes with directing groups, such as ester, amide, sulfonate, acetal, alkoxymethyl, and chloro groups, under mild reaction conditions.

Rh-Catalyzed Ortho-Selective C–H Borylation of N-Functionalized Arenes with Silica-Supported Bridgehead Monophosphine Ligands

Supported phosphine-Rh systems, prepared in situ from silica-supported bridgehead monophosphines and [Rh(OH)(cod)](2), have enabled ortho-selective C-H borylation for a range of arenes containing nitrogen-based directing groups. The regioselectivity was excellent with various N-directing groups, including saturated and unsaturated N-heterocycles, tert-aminoalkyl groups, and imine-type C-N double bonds. The reaction showed significant tolerance toward steric repulsion around the reacting C-H bond. This Rh catalysis complements the Ir-catalyzed ortho-borylation, which is effective for arenes with oxygen-based directing groups.

Directed Ortho Borylation of Phenol Derivatives Catalyzed by a Silica-Supported Iridium Complex

The directed ortho borylation of phenol derivatives protected with an N,N-diethylcarbamoyl group was efficiently catalyzed by an immobilized monophosphine-Ir system, which was prepared in situ from [Ir(OMe)(cod)](2) and a silica-supported, compact phosphine. The utility of the carbamoyloxy group as a leaving group for metal-catalyzed cross-coupling reactions was demonstrated by its utilization in the synthesis of a terphenyl derivative.

Rh-Catalyzed Borylation of N-Adjacent C(sp3)–H Bonds with a Silica-Supported Triarylphosphine Ligand

Direct C(sp(3))-H borylation of amides, ureas, and 2-aminopyridine derivatives at the position α to the N atom, which gives the corresponding α-aminoalkylboronates, has been achieved with a heterogeneous catalyst system consisting of [Rh(OMe)(cod)]2 and a silica-supported triarylphosphine ligand (Silica-TRIP) that features an immobilized triptycene-type cage structure with a bridgehead P atom. The reaction occurs not only at terminal C-H bonds but also at internal secondary C-H bonds under mild reaction conditions (25-100 °C, 0.1-0.5 mol % Rh).

Synthesis of Primary and Secondary Alkylboronates through Site-Selective C(sp3)–H Activation with Silica-Supported Monophosphine–Ir Catalysts

The site-selective activation and borylation of unactivated C(sp(3))-H bonds in 2-alkylpyridines to form primary and secondary alkylboronates was achieved using silica-supported monophosphine-Ir catalysts. This borylation occurs selectively at C-H bonds located γ to the pyridine nitrogen atom. The site-selectivity of this reaction suggests that the C-H bond cleavage occurs with the assistance of a proximity effect due to N-to-Ir coordination.

Palladium-Catalyzed Borylation of Sterically Demanding Aryl Halides with a Silica-Supported Compact Phosphane Ligand†

Arylboronic acid derivatives are versatile intermediates in organic synthesis because of their broad availability, air stability, and ease of handling. Among the routes to arylboronic acid derivatives, the conventional methods that use aryllithium or Grignard reagents have a problem with functional-group compatibility. More recently, functionalgroup-tolerating approaches such as the transition-metalcatalyzed borylation of aryl halides 3] and the direct C H borylation of arenes have been introduced, and both are complementarily applicable to the preparation of a wide range of arylboronates. Specifically for the borylation of aryl halides, aryl chlorides are the most desirable substrates because of their low cost and broad availability; however, they are less reactive than the corresponding bromides, iodides, and triflates. Accordingly, only a few catalyst systems are effective for reactions of unactivated aryl chlorides. A common feature of effective systems is the use of electronrich and sterically demanding phosphane ligands in combination with a palladium source. The most efficient catalyst systems reported to date are those based on (dicyclohexylphosphino)biphenyl-type ligands such as SPhos and XPhos, which were originally described by Buchwald and co-workers. The use of these catalysts allowed for the borylation of sterically or electronically challenging aryl chlorides such as 1-chloro-2,6-dimethylbenzene (2 mol% Pd/SPhos, RT, 86%) and 4-chloroanisole (0.1 mol% Pd/XPhos, 110 8C, 94 %). Buchwald and co-workers described that the efficacy of biphenyl-type ligands for the borylation is attributed at least in part to their sterically demanding nature, which promotes the formation of a highly reactive 1:1 Pd/P complex over less reactive 1:2 Pd/P species. 5] On the other hand, we have developed Silica-SMAP, which is a silica-supported “compact” phosphane ligand. 7] Because of its immobilized nature, this ligand forms 1:1 metal/P complexes exclusively with a range of transition-metal species, despite its extreme compactness. We demonstrated that the surface-bound 1:1 metal/P complexes afford highly active catalysts for the hydrosilylation and the hydrogenation of ketones (with Rh), and the directed ortho borylation of functionalized arenes (with Ir). In particular, these reactions showed remarkable tolerance toward the reactions of sterically demanding substrates. Accordingly, we envisioned that, despite its compactness, the supported phosphane would be useful in creating a highly active catalytic environment for the palladium-catalyzed borylation of sterically or electronically challenging aryl halides. 8, 9] Furthermore, this utility means that the steric demand of a ligand would not be essential for the high catalytic activity in the palladium-catalyzed borylation of aryl chlorides, as has been proved by the experiments described below. The reaction of 4-chlorotoluene (1 a, 0.5 mmol) with bis(pinacolato)diboron (2, 0.5 mmol) in the presence of Pd(OAc)2 (0.5 mol %), Silica-SMAP (0.5 mol %), and KOAc (3 equiv) in benzene at 60 8C for 10 h gave the desired arylboronate 3a in 84% yield, but the reaction also formed a significant amount of biaryl compound 3a’ (8% yield), which likely resulted from a Suzuki–Miyaura coupling between the arylboronate product 3a and aryl chloride 1a (Scheme 1, catalyst precursor A). The undesired biaryl formation was almost completely inhibited by using the Silica-SMAP/Pd system that was prepared in advance (from Silica-SMAP and [PdCl2(cod)], P/Pd = 1:1, catalyst precursor B), instead of the in situ generated complex (catalyst precursor A); 3a was thus produced in an excellent yield (Scheme 1). Furthermore, another preformed complex Silica-SMAP/[PdCl2(pyridine)2] afforded exclusively the borylation product 3a, albeit in a lower conversion (Scheme 1, catalyst precursor C). It should

Iridium-catalyzed C–H borylation of quinolines and unsymmetrical 1,2-disubstituted benzenes: insights into steric and electronic effects on selectivity

Borylation of quinolines provides an attractive method for the late-stage functionalization of this important heterocycle. The regiochemistry of this reaction is dominated by steric factors but, by undertaking reactions at room temperature, an underlying electronic selectivity becomes apparent, as exemplified by the comparative reactions of 7-halo-2-methylquinoline and 2,7-dimethylquinoline which afford variable amounts of the 5- and 4-borylated products. Similar electronic selectivities are observed for nonsymmetrical 1,2-disubstituted benzenes. The site of borylation can be simply estimated by analysis of the 1H NMR spectrum of the starting material with preferential borylation occurring at the site of the most deshielded sterically accessible hydrogen or carbon atom. Such effects can be linked with C–H acidity. Whilst DFT calculations of the pKa for the C–H bond show good correlation with the observed selectivity, small differences suggest that related alternative, but much more computationally demanding values, such as the M–C bond strength, may be better quantitative predictors of selectivity.

Hydrogenation of Hindered Ketones Catalyzed by a Silica-Supported Compact Phosphine−Rh System

A heterogeneous mono(phosphine)-Rh catalyst system silica-SMAP-Rh(OMe)(cod), where silica-SMAP stands for a caged, compact trialkylphosphine (SMAP) supported on silica gel, showed broad applicability toward the hydrogenation of hindered ketones. Doubly alpha-branched ketones such as diisopropyl ketone was hydrogenated under nearly atmospheric conditions. Di-tert-butyl ketone could be hydrogenated under more forcing conditions.

[Silica]-SMAP-Rh System for the Hydrosilylationof Hindered Ketones

hydrosilylation G . H A M A S A K A , S . K AW A M O R I T A , A . O C H I D A , R . A K I Y A M A , K . H A R A , A . F U K U O K A , K . S A K U R A , W. J . C H U N , H . O H M I Y A , M . S A WA M U RA * ( H O K K A I D O U N IVE R S I T Y, S A P P O R O A N D I N T E RN A T I O N A L C H R IS T I A N U N IV E R S I T Y, TO K Y O , J A P A N ) Synthesis of Silica-Supported Compact Phosphines and Their Application to Rhodium-Catalyzed Hydrosilylation of Hindered Ketones with Triorganosilanes Organometallics 2008, 27, 6495-6506.