Why You Really Should Consider Using Palladium-Catalyzed Cross-Coupling of Silanols and Silanolates

Abstract

The transition metal-catalyzed cross-coupling of organometallic nucleophiles derived from tin, boron, and zinc with organic electrophiles enjoys a preeminent status among modern synthetic methods for the formation of carbon-carbon bonds. In recent years, organosilanes have emerged as viable alternatives to the conventional reagents, with the added benefits of low cost, low toxicity and high chemical stability. However, silicon-based cross-coupling reactions often require heating in the presence of a fluoride source, which has significantly hampered their widespread acceptance. To address the “fluoride problem”, a new paradigm for palladium-catalyzed, silicon-based cross-coupling reactions has been developed that employs a heretofore underutilized class of silicon reagents, the organosilanols. The use of organosilanols, either in the presence of Brønsted bases or as their silanolate salts, represents an operationally simple and mild alternative to the fluoride-based activation method. Organosilanols are readily available by many well-established methods for introducing carbon-silicon bonds onto alkenes, alkynes, arenes and heteroarenes. Moreover, several different protocols for the generation of alkali metal salts of, vinyl-, alkenyl-, alkynyl-, aryl-, and heteroarylsilanolates have been developed and the advantages of each of these methods have been demonstrated for a number of different coupling classes. This review will describe the development and implementation of cross-coupling reactions of organosilanols and their conjugate bases, silanolates, with a wide variety of substrate classes. In addition, application of these transformations in the total synthesis of complex natural products will also be highlighted. Finally, the unique advantages of organosilicon coupling strategies vis a vis organoboron reagents are discussed.

Palladium‐Catalyzed Defluorinative Coupling of 1‐Aryl‐2,2‐Difluoroalkenes and Boronic Acids: Stereoselective Synthesis of Monofluorostilbenes

“…Second, the reaction conditions are uniquely suited to boron-based nucleophiles,i ncluding boronic acids and potassium tetrafluoroborate salts (Scheme 3, footnote [e]), although boronic esters react sluggishly.Interestingly,we found that arylstannanes and arylsilanes were inert under our reaction conditions both with and without added equivalents of fluoride,t hus affording the opportunity for orthogonal cross-coupling. [14] Finally,avariety of functional groups were tolerated and might be useful for further synthetic manipulations.I mportantly,a rylhalides were tolerated under these reaction conditions,i ncluding chlorides,b romides,a nd iodide.E ven as ubstrate bearing a2 -bromopyridine was tolerated. In no case was there cross-coupling with these functional groups, and it stands in stark contrast to the previously described nickel-catalyzed procedure which also produced competitive aryl halide cross-coupling,e ven with arylchlorides.…”

Cooperative redox activation for carbon dioxide conversion

“…After an exhaustive optimization study (Supplementary Tables 1–4) we identified catalytic reaction conditions involving Pd(acac) 2 (acac, acetylacetonate) as the palladium source, 4,4′-dimethylbipyridine (4-Mebipy) as the ligand and finally cesium fluoride (CsF) and copper(I) 3-methyl salicylate (Cu(3-MeSal)) as promoters for the transmetalation step in DMF providing an excellent 81% yield of the diarylketone 3 . A reaction temperature of 110 °C was required for full conversion, which is considerably higher than that observed for the normal Hiyama-Denmark coupling with aryl iodides, and which can be explained by an attenuated reactivity of the palladium catalyst with CO as a ligand23.…”

“…We questioned whether the oxidized silicon waste product generated from the reduction of CO 2 to CO with a disilane could instead be viewed as a reagent for an ensuing second chemical transformation along with the produced CO. We recognized that oxygen abstraction from CO 2 would generate a disiloxane, which if substituted with aryl groups would act as an aryl delivering agent in a Pd-catalysed Hiyama-Denmark coupling with a (hetero)aryl halide (Fig. 1b)2223. Furthermore, we reasoned that if the CO could be exploited then non-symmetrical diarylketones would be made accessible for the first time through a modified three-component Hiyama-Denmark coupling in a single operation (Fig.…”

Trifluoromethylation of Arylsilanes with [(phen)CuCF3]

“…[15] Recent advances in the regioselective, catalytic silylation of C-H bonds in unactivated arenes and heteroarenes have greatly expanded the accessibility of arylsilanes. [16–19] The silylation of C-H bonds forms arylsilanes with regioselectivities that are enhanced or distinct from those of C-H borylation.…”