The first example of enantioselective enolate α‐oxygenation was reported in 1988 by Shioiri (Scheme 4.20) [73]. A chiral cinchoninium catalyst was found to promote the α‐oxygenation of indanones with moderate enantioselectivity from an in situ generated electrophilic hydroperoxide formed from triethylphosphite and molecular oxygen.
In 2008, 20 years after the seminal report by Shiori, Itoh disclosed a related system that proved to be highly enantioselective using an anthracene‐functionalized chiral cinchoninium catalyst (Scheme 4.21) [74]. In the years following these reports, numbers of related systems have been reported using other electrophilic oxygenating reagents such as hydroperoxides or oxaziridines [75].
In 2008, Maruoka reported the first example of phase‐transfer catalyzed α‐amination of enolate derivatives. Specifically, β‐ketoesters could be aminated in high enantioselectivity using diazocarboxylates as electrophilic aminating reagents and a chiral tetraalkylphosphonium catalyst (Scheme 4.22) [76]. Notably, this was a pioneering example of the use of a chiral tetraalkylammonium catalyst in phase‐transfer catalysis. The same group disclosed a year later that a more selective spirocyclic chiral ammonium catalyst could also promote this reaction at lower catalyst loadings [77]. A similar strategy was disclosed in 2011 by Ma [78] and later in 2019 by Maruoka [79] for the enantioselective amination of oxindoles and benzofuranones (Scheme 4.23). Ma’s system used a quaternary phosphonium catalyst and Maruoka’s system used a spirocyclic ammonium catalyst, both featuring chiral C2‐symetric binaphthyl backbones.
Scheme 4.21. Enantioselective α‐hydroxylation of oxindoles.
Source: Based on [74].
Scheme 4.22. Enantioselective α‐amination of β‐ketoesters using azodicarboxylates.
While diazocarboxylates proved to be suitable electrophilic amination reagents for phase‐transfer‐catalyzed enolate α‐amination to form hydrazine derivatives, subsequent reductive N–N bond cleavage is required to unmask the free amine. In 2016, Ooi disclosed an elegant system wherein direct amination is achieved using an electrophilic aminating reagent formed in situ from the corresponding hydroxylamine and trichloroacetonitrile (Scheme 4.24) [80]. Notably, a triazolium‐based chiral phase‐transfer catalyst was optimal, providing α‐aminated oxindoles with high enantioselectivity.
4.2.2. Transition‐Metal/Chiral Cation Dual Catalysis
Asymmetric transition‐metal catalysis has traditionally relied on the use of chiral ancillary ligands to modulate the metal’s primary coordination sphere to directly influence enantioselectivity. In recent years, a distinct strategy has emerged wherein ion‐pairing interactions at a metal’s secondary coordination sphere can influence enantioselectivity. Given that cationic metal complexes are more common than their anionic counterparts in catalysis, implementation of this strategy using chiral‐anions has seen more progress and will be discussed in detail in Section 3.6. Conversely, ion‐pairing between a chiral cation and an anionic metal complex has also been reported. In 2016, Tan reported the use of a dinuclear peroxomolybdate anionic oxidant ion‐paired to a chiral bisguanidinium dication catalyst for the enantioselective oxidation of various sulfides to the corresponding sulfoxides (Scheme 4.25) [81]. This proposed catalytically relevant ion‐pair was isolable and characterized by single‐crystal X‐ray diffraction. The same year, a related system was reported by the same group using a tungstate catalyst and the identical chiral bisguanidinium catalyst [82]. Prior to this work, chiral cationic catalysts had been reported to ion‐pair with anionic metal complexes such as permanganate anions when used stoichiometrically [83, 84].
Scheme 4.23. Enantioselective α‐amination of oxindoles and lactones using azodicarboxylates.
Scheme 4.24. Enantioselective α‐amination of oxindoles using hydroxylamines.
Source: Based on [80].
Scheme 4.25. Enantioselective oxidation of sulfides using a peroxomolybdate/chiral cation ion pair catalyst.
Source: Based on [81].
Scheme 4.26. Enantioselective transformations via transition metal/chiral cation ion pairing catalysis.
The asymmetric addition of alkynyl nucleophiles to carbonyl‐containing compounds represents a powerful approach to form chiral propargyl alcohols. In 2019, Maruoka demonstrated that a chiral ammonium catalyst could ion‐pair with a catalytically generated Ag‐alkynylide for the enantioselective addition to isatin derivatives (Scheme 4.26) [85]. While chiral ion‐pairing and phase‐transfer catalyses have typically involved ion‐pairing with an enolate nucleophile, this represents a unique example where an alternative carbon‐based nucleophile can be productively used via the use of a transition‐metal co‐catalyst. In 2020, the Phipps group disclosed an elegant system for the desymmetrization of geminal diaryl derivatives via enantioselective Ir‐catalyzed C–H borylation [86]. The key ion‐pairing between a strategically placed sulfonate group on the bipyridine ligand backbone and a chiral cinchoninium cation enables the enantioselective meta‐selective borylation of prochiral diaryl substrates. This work is particularly significant as it represents a rare example of remote asymmetric induction, where the site of the newly formed C–B bond is far from the newly formed chiral center. Looking forward, the strategy of incorporating chiral ion‐pairing interactions in ligand design for metal‐catalyzed transformations is positioned to have significant impact for the development of new