Recent Developments and Synthetic Applications of Nucleophilic Zirconocene Complexes from Schwartz's Reagent

Abstract

Organozirconium chemistry has been widely employed in organic synthesis since its discovery in the last century. In this context, Schwartz's reagent stands out as a powerful tool that has been applied in several chemical transformations. This chemistry has attracted considerable attention due to its versatility, allowing chemoselective C–C, C–N, and C–X bond formation, as well as hydrozirconation. The reagent is in fact a zirconium‐containing metallocene, which is compatible with the presence of various metals in cross‐coupling reactions. Enantioselective transformations of organozirconium are described here, which have recently found wide applications in total synthesis. Furthermore, aspects covering ring‐closure reactions, affording complex stereoenriched cycles and heterocycles, such as substituted cyclopropanes and pyrrolidines, are hereby disclosed.

Characterization of Reactive Organometallic Species via MicroED

“…We first interrogated the structure of chloridobis­(η 5 -cyclopentadienyl)­hydridozirconium 1 (Figure A), a well-known industrial catalyst colloquially referred to as Schwartz’s reagent. Schwartz’s reagent sees widespread use in modern organic synthesis and is useful for a number of unique transformations mediated via hydrozirconation intermediates. − However, despite its synthetic relevance and the countervailing fact that half a century has transpired since Wailes and Weigold first discovered this species, , no single crystal structure of this canonical zirconocene complex has been obtained. This gap in crystallographic data has been attributed to the low solubility of the complex in hydrocarbon and ethereal solvents and its reactivity with polar chlorinated solvents, precluding its crystallization and hindering NMR studies.…”

Characterization of reactive organometallic species via MicroED

“…Schwartz's reagent sees widespread use in modern organic synthesis and is useful for a number of unique transformations mediated via hydrozirconation intermediates. 4,5,6 However, despite its synthetic relevance and the countervailing fact that half a century has transpired since Wailes and Weigold first discovered this species, 7,8 no single crystal structure of this canonical zirconocene complex has been obtained. This gap in crystallographic data has been attributed to the low solubility of the complex in hydrocarbon and ethereal solvents and its reactivity with polar chlorinated solvents, 9 precluding its crystallization and hindering NMR studies.…”

Are Organozirconium Reagents Applicable in Current Organic Synthesis?

“…25 Their reactivity is lower in comparison to conventional organometallics such as Grignard, organozinc or organoaluminum reagents, which allows their handling at room temperature and the preparation of functionalized reagents. As the main advances in the application of organozirconium species 4 and 5 in organic synthesis and asymmetric methodology have been neatly covered by Amarante, 26 we aim here to provide an outline of more recent or otherwise overlooked discoveries. In addition to Amarante, Wieçław and Stecko elegantly covered the reducing capabilities of the Schwartz reagent (1) towards C=X functionalities.…”