Robert E. Maleczka

High-Throughput Optimization of Ir-Catalyzed C–H Borylation: A Tutorial for Practical Applications

With the aid of high-throughput screening, the efficiency of Ir-catalyzed C-H borylations has been assessed as functions of precatalyst, boron reagent, ligand, order of addition, temperature, solvent, and substrate. This study not only validated some accepted practices but also uncovered unconventional conditions that were key to substrate performance. We anticipate that insights drawn from these findings will be used to design reaction conditions for substrates whose borylations are difficult to impossible using standard catalytic conditions.

A Traceless Directing Group for C! H Borylation**

Not a trace: Borylation of the nitrogen in nitrogen heterocycles or anilines provides a traceless directing group for subsequent catalytic C-H borylation. Selectivities that previously required Boc protection can be achieved; furthermore, the NBpin directing group can be installed and removed in-situ, and product yields are substantially higher. Boc=tert-butoxycarbonyl, pin=pinacolato.

Outer-Sphere Direction in Iridium C–H Borylation

The NHBoc group affords ortho selective C-H borylations in arenes and alkenes. Experimental and computational studies support an outer sphere mechanism where the N-H proton hydrogen bonds to a boryl ligand oxygen. The regioselectivities are unique and complement those of directed ortho metalations.

Electronic effects in iridium C-H borylations: insights from unencumbered substrates and variation of boryl ligand substituents.

Experiment and theory favour a model of C-H borylation where significant proton transfer character exists in the transition state.

Silyl phosphorus and nitrogen donor chelates for homogeneous ortho borylation catalysis.

Ir catalysts supported by bidentate silyl ligands that contain P- or N-donors are shown to effect ortho borylations for a range of substituted aromatics. The substrate scope is broad, and the modular ligand synthesis allows for flexible catalyst design.

Boc Groups as Protectors and Directors for Ir-Catalyzed C−H Borylation of Heterocycles

Ir-catalyzed C-H borylation is found to be compatible with Boc protecting groups. Thus, pyrroles, indoles, and azaindoles can be selectively functionalized at C-H positions beta to N. The Boc group can be removed on thermolysis or left intact during subsequent transformations.

C−O Hydrogenolysis Catalyzed by Pd-PMHS Nanoparticles in the Company of Chloroarenes

Catalytic Pd(OAc)(2) and polymethylhydrosiloxane (PMHS), in conjunction with aqueous KF, and a catalytic amount of an aromatic chloride, effects the chemo-, regio-, and stereoselective deoxygenation of benzylic oxygenated substrates at room temperature in THF. Preliminary mechanistic experiments suggest the process to involve palladium-nanoparticle-catalyzed hydrosilylation followed by C-O reduction. The chloroarene additive appears to facilitate the hydrogenolysis process through the slow controlled release of HCl.

Room temperature dehalogenation of chloroarenes by polymethylhydrosiloxane (PMHS) under palladium catalysis

The first method for the reduction of chloroarenes by polymethylhydrosiloxane (PMHS) is reported. Catalytic amounts of palladium(II) acetate in combination with PMHS and aqueous KF will rapidly hydrodehalogenate aryl chlorides at room temperature. The mildness of the method is demonstrated by its tolerance of ketones, amides, esters, nitriles, ethers, borate esters, and amines.

Iridium-catalyzed borylation of thiophenes : versatile, synthetic elaboration founded on selective C-H functionalization

Iridium-catalyzed borylation has been applied to various substituted thiophenes to synthesize poly-functionalized thiophenes in good to excellent yields. Apart from common functionalities compatible with iridium-catalyzed borylations, additional functional group tolerance to acyl (COMe), and trimethylsilyl (TMS) groups was also observed. High regioselectivities were observed in borylation of 3-and 2,5-di-substituted thiophenes. Electrophilic aromatic C-H/C-Si bromination on thiophene boronate esters is shown to take place without breaking the C-B bond, and one-pot C-H borylation/Suzuki-Miyaura cross-coupling has been accomplished on 2- and 3-borylated thiophenes.

Getting the sterics just right: a five-coordinate iridium trisboryl complex that reacts with C-H bonds at room temperature

Five-coordinate boryl complexes relevant to Ir mediated C-H borylations have been synthesized, providing a glimpse of the most fundamental step in the catalytic cycle for the first time.