Ruthenium-catalyzed C–H Silylation of Methylboronic Acid Using a Removable α-Directing Modifier on the Boron Atom

Abstract

Ruthenium-catalyzed CH silylation of methylboronic acid was achieved by use of 2-(1H-pyrazol-3-yl)aniline as a removable ¡-directing modifier on the boron atom. Crosscoupling of the product, i.e., (phenyldimethylsilyl)methylpinacolborane, with aryl halides proceeded in the presence of a [PdCl 2 (dppf)] catalyst and CsOH as a base.Directed catalytic functionalization of the sp 3 -CH bond is an attractive strategy for the synthesis of functionalized alkanes in organic synthesis.1 Functional groups such as pyridyl, quinolinyl, oxazolinyl, carboxyl, aminocarbonyl, and imino groups are attached to alkanes as directing groups for CH functionalization through arylation, 2 amination, 3 silylation, 4 acetoxylation, 5 halogenation, 6 etc. Despite the remarkable acceleration of the catalytic reaction by the directing groups, the need for their installation in the substrates significantly limits the scope of the reaction. It is likely that the development of "traceless" or "convertible" directing groups will make directed CH activation really useful and applicable to organic synthesis. 7 We have developed removable o-directing groups, which are attached to the boron atoms of arylboronic acids, for Ru-catalyzed o-CH silylation at their sp 2 -carbon atoms. 2-(1H-Pyrazol-3-yl)aniline and anthranilamide form six-membered diazaborine structures 1 and 2 containing NBN linkages upon condensation with arylboronic acids. 8,9 The nitrogen atoms in the attached directing group coordinate to the transition-metal catalysts and enable the CH functionalization at the orthopositions. It would be highly attractive if the strategy could be extended to activation of alkylboronic acids. In particular, such a synthetic strategy is most attractive for the synthesis of ¡-functionalized methylboronic acids (Figure 1), because they are not accessible by hydroboration unlike the higher alkylboronic acids. It has been shown that even strong bases are not able to abstract ¡-hydrogen atoms of methylboronic acid esters.10 It should be noted that, in spite of its potential usefulness, no catalytic CH-functionalization at the ¡-hydrogen of alkylboronic acids has been reported. Herein, we describe ¡-CH silylation of methylboronic acid using an ¡-directing modifier that is attached to the boron atom.Methylboronic acid was condensed with 2-(1H-pyrazol-3-yl)aniline and anthranilamide, giving MeB(pza) (1) and MeB(aam) (2), respectively, in high yields (eqs 1 and 2). A phenol analog MeB(pzp) (3) of 1 was also prepared by the reaction with commercially available 2-(1H-pyrazol-3-yl)phenol in high yield (eq 1). The modified methylboronic acids 13 were subjected to Ru-catalyzed reaction with triorganosilanes in the presence of norbornene as a hydrogen scavenger (Table 1).11 With the [RhCl(cod)] 2 catalyst, a trace amount of the expected ¡-silylation product was detected by 1 H NMR (Entry 1). Ruthenium catalysts were found to be more effective for ¡-silylation. The [RuH 2 (CO)(PPh 3 ) 3 ] catalyst, which served as the best catalyst in the o-CH silylation of PZA-and ...

Direct silylation reactions of inert C-H bonds via transition metal catalysis

“…Almost at the same time, a Ru-catalyzed C-H silylation reaction of methylboronic acid with hydrosilanes using a removable directing group, 2-pyrazol-5-ylaniline (pza), was reported by Suginome et al (Scheme 31) [32]. [RuH 2 (CO) (PPh 3 ) 3 ] showed the best performance among the catalysts screened.…”

Site‐Selective Aliphatic C−H Silylation of 2‐Alkyloxazolines Catalyzed by Ruthenium Complexes

“…Despite the success of the aromatic C(sp 2 )−H silylation, examples of the intermolecular silylation of aliphatic C(sp 3 )−H bonds, to our knowledge, are still rare to date (Scheme ). Since the pioneering work on benzylic C(sp 3 )−H silylation by Kakiuchi and co‐workers, the C(sp 3 )−H silylation of methylboranes and that of methylamines have been reported by others. That is, the examples of directed C(sp 3 )−H silylation have hitherto been limited to cases where there are additional activations by α‐position atoms.…”

“…Since the pioneering work on benzylic C(sp 3 )ÀHs ilylation by Kakiuchia nd co-workers, [2] the C(sp 3 )ÀHs ilylation of methylboranes [3] and that of methylamines [4] have been reported by others. That is, the examples of directed C(sp 3 )ÀHs ilylation have hitherto been limited to cases where there are additional activationsb ya-position atoms.D uring the preparation of this manuscript, the C(sp 3 )ÀHs ilylation of 2-ethylpyridines with Et 3 SiH was published;h owever,t he a-position amino group was not tolerated.…”

“…The present study demonstrates that 1 is an efficient silylating reagent for the C(sp 3 )ÀHs ilylation;h owever, in place of 1,t he use of Et 3 SiH induced ad rastic lowering of the reactivity (entry 12) andt hat of (Me 3 SiO)Me 2 SiHl ed to complex mixtures (entry 13). Furthermore, no reactionw ith (EtO) 3 SiH or with Me 2 ClSiH occurred, presumably because of disproportionation of the silanes( entries 14 and 15). As shown in Table 1, the present successprobably relies on the use of 1.W eb elieve that not only the thermal stabilityr esulting from the steric bulk of the SiMe(OSiMe 3 ) 2 group, but also the electronic effect of the two OSiMe 3 groups on the silicon atom play an important role in the C(sp 3 )ÀHs ilylation.…”

Iridium‐Catalyzed Regioselective Silylation of Aromatic and Benzylic CH Bonds Directed by a Secondary Amine

“…As a result of the steric hindrance, the reactivity of secondary CH bonds is typically lower than that of primary CH bonds when an organometallic intermediate is generated, and the examples of the high‐yielding silylation of secondary CH bonds are rare 6h. 9c,e, 11c Nevertheless, the amine‐directed silylation of secondary benzylic CH bonds occurred in good to excellent yields ( 6 f – h and 7 i – l , Table 3). In some cases, longer reaction times ( 7 i ) or higher temperatures ( 7 j – l ) were required (Table 3).…”