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

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 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-à-vis organoboron reagents are discussed.