Hydrogen‐Bonding‐Assisted Cationic Aqua Palladium(II) Complex Enables Highly Efficient Asymmetric Reactions in Water

Abstract

Metal‐bound water molecules have recently been recognized as a new facet of soft Lewis acid catalysis. Herein, a chiral palladium aqua complex was constructed that enables carbon–hydrogen bonds of indoles to be functionalized efficiently. We embraced a chiral 2,2′‐bipyridine as both ligand and hydrogen‐bond donor to configure a robust, yet highly Lewis acidic, chiral aqua complex in water. Whereas the enantioselectivity could not be controlled in organic solvents or under solvent‐free conditions, the use of aqueous environments allowed the σ‐indolylpalladium intermediates to react efficiently in a highly enantioselective manner. This work thus describes a potentially powerful new approach to the transformation of organometallic intermediates in a highly enantioselective manner under mild reaction conditions.

Recent Advances on Direct Functionalization of Indoles in Aqueous Media

“…The newly designed LPd(OTf) 2 complex enabled enantioselective control through an efficient and simple protocol. [90] In 2019, Ma's group also achieved the synthesis of similar structures mentioned above. [91] The Friedel-Crafts alkylation of indole in water was realized by designing and synthesizing a new amphiphile featuring two NHSO 2 C 4 F 9 sites as a Brønsted diacid catalyst (Scheme 20).…”

Synthetic Organic “Aquachemistry” that Relies on Neither Cosolvents nor Surfactants

“…The immense role played by water in determining enantiocontrol was also revealed for palladium-catalyzed indole C–H functionalization via the putative σ-indolylpalladium intermediate (Table ). Notably, substrates reacted in a highly enantioselective manner in water despite being immiscible (Type IIIa reaction). The reaction suffered from a significant reduction of enantioselectivity when run either in organic solvents or under solvent-free conditions.…”

Recent Advances in Selected Asymmetric Reactions Promoted by Chiral Catalysts: Cyclopropanations, Friedel–Crafts, Mannich, Michael and Other Zinc-Mediated Processes—An Update

“…The processes were catalyzed by PyBox [43] or iPrBox [44], respectively (Scheme 16). The asymmetric reaction of indoles with α,β-unsaturated carbonyl compounds 45 (enones) was carried out using three similar catalytic systems (Scheme 17) [45][46][47]. In the first contribution, reaction was promoted by imidazoline-oxazoline 46 complex with Cu(OTf) 2 (acetonitrile, room temperature), leading to indole derivatives acting as novel α-glucosidase inhibitors in vitro [45].…”

“…In the first contribution, reaction was promoted by imidazoline-oxazoline 46 complex with Cu(OTf) 2 (acetonitrile, room temperature), leading to indole derivatives acting as novel α-glucosidase inhibitors in vitro [45]. The second approach comprises a utilization of chiral N,N-dioxide 47-scandium(III) complexes in dichloromethane at 35 • C [46], and finally, the third work relies on the application of cationic aqua complex of 2,2 -bypiridine 48 with palladium(II) in water at room temperature [47]. Similar dinuclear zinc catalytic systems were also used in the synthesis of 2,5-pyrrolidinyl dispirooxindoles [51] and tetrahydrofuran spirooxindoles [52] via cascade reactions, where one of the steps is a Friedel-Crafts process.…”