Cation‐Binding Catalysis
Since the discovery of the cation‐binding properties of cyclic polyethers, there has been a desire to utilize this class of compounds to impart enantioselectivity onto a reaction by utilizing a chiral crown ether. The first example of this concept was demonstrated by Cram in 1981, with the asymmetric Michael addition of a cyclic β‐keto ester into methyl vinyl ketone (MVK) with a BINOL‐derived 22‐crown‐6 catalyst (Scheme 4.27) [87]. In this example, a chiral crown ether acts as a phase‐transfer catalyst for KOtBu. After deprotonation of the substrate, a potassium‐bound crown ether cation is ion‐paired with an enolate, allowing for enantioselective addition to methyl vinyl ketone (MVK).
Since the initial report by Cram, focus in the field of cation‐binding catalysis shifted to utilizing crown ether catalysts derived from carbohydrates. In 1989, a highly symmetric polyether catalyst was reported that catalyzed an asymmetric Michael addition of methyl phenyl acetate to methyl acrylate in high yield and moderate enantioselectivity (Scheme 4.28) [88]. In 1997, the Bakó group reported that an aza‐crown ether catalyst derived from D‐glucose catalyzed a nitro‐Michael reaction in high enantioselectivity [89]. This catalyst architecture proved to be applicable in various asymmetric phase‐transfer settings, such as in glycine imine[90] and aminomethylene phosphonate alkylation[91], as well as asymmetric chalcone epoxidation [92].
In 2009, the Song group demonstrated a novel polyether catalyst based on the BINOL scaffold that competently bound and phase‐transferred KF (Scheme 4.29) [93]. This catalyst was effective for the kinetic resolution of silyl‐protected alcohols via desilylation [94]. A 2015 follow‐up publication revealed that this catalyst architecture was competent for the reverse‐reaction, where an alcohol was kinetically resolved by silylation with the catalyst [95]. In early 2016, the Yan group applied this system to kinetic resolution via an E1cB‐elimination of β‐sulfonyl ketones [96]. Over the next several years, numbers of other kinetic resolutions featuring various leaving groups were shown to be compatible with this strategy, such as poly halogenated ketones[97], and aldols [98].
In addition to initiation with KF, in 2012, an organocatalytic asymmetric Strecker reaction was developed utilizing BINOL‐derived crown ether with KCN (Scheme 4.30) [99]. The functionalization of α‐amidosulfones proved to be a valuable paradigm, as many compatible anions were demonstrated to perform Mannich reactivity in high yields and selectivities. Notable nucleophiles include fluoro‐oxindoles [100], indoles [101], fluoroketones [102], thiocyanato ketones [103], and phthalimides [104]. In addition to kinetic resolutions, this system was also found to be useful for the synthesis of cyclic compounds from unsaturated ketones, such as with nitrones [105], mercaptoacetaldehyde [106], or intramolecular exo‐trig cyclizations [107].
Scheme 4.27. Asymmetric Michael addition via cation binding BINOL‐derived ether catalysts.
Source: Based on [87].
Scheme 4.28. Enantioselective Michael addition via cation binding sugar‐derived ether catalysts.
Source: Based on [88].
Scheme 4.29. Kinetic resolution of silyl‐protected alcohols.
Source: Based on [93].
4.3. CHIRAL‐ANION
The developments in the field of chiral cation phase‐transfer and ion‐pairing catalyses have displayed immense advancements for the field of catalysis. Despite the long history of this mode of catalysis, the charged‐reversed version, chiral‐anion catalysis, has been a significantly more recent development. This mode of activation centers on utilizing chiral‐anions to impart enantioselectivity on cationic intermediates and reagents via ion‐pairing. One advantage of this strategy is the orthogonal reactivity that can be achieved by focusing on transformations that feature cationic intermediates from relatively unactivated starting materials under mild conditions.
Scheme 4.30. Asymmetric Strecker reaction catalyzed by BINOL‐derived crown ether.
Source: Based on [99].
4.3.1. Iminium
The first proof of principal example of utilizing ion‐pairing catalysis with a chiral‐anion was demonstrated by the List group in 2006 (Scheme 4.31) [108]. In this example, an ammonium/chiral phosphate salt would catalyze the enantioselective reduction of enals with Hantzsch ester. The key intermediate for imparting enantioselectivity is the iminium formed from condensation of the achiral ammonium and the enal, which remains ion‐paired with a (R)‐TRIP counteranion. This ion‐pair leads to preferential reduction of one face of the alkene by Hantzsch ester, leading to β‐chiral ketones in high yields and enantioselectivities. Following this, the List group utilized this key intermediate for the epoxidation of di‐ and tetrasubstituted enals by using t‐butyl hydroperoxide [109]. It was found that the identity of the achiral ammonium had a profound effect on the observed enantioselectivities (24–90% ee), where dibenzylic ammoniums with electron deficient arenes provided the best enantioselectivities. This demonstrates the importance of tuning both components of the ion‐pair for cooperatively achieving high selectivities, and is a key feature in many examples of chiral‐anion catalysis.
In addition to ammonium/chiral phosphoric acid salts, a variety of catalyst architectures can be utilized for generating iminium intermediates that are amenable to chiral‐anion catalysis. In 2013, the Masson group demonstrated that an iminium intermediate could be generated from protonation and subsequent dehydration of γ‐hydroxy‐γ‐lactams by a chiral phosphoric acid (Scheme 4.32) [110]. The resulting iminium intermediate underwent asymmetric C3‐arylation with indoles in high yields and enantioselectivities. Other catalysts not based on BINOL phosphoric acids have been demonstrated to be competent for chiral‐anion catalysis. Notable examples include a novel conjugate‐based stabilized carboxylic acid that catalyzes an enantioselective three‐component Povarov reaction[111], and an ammonium/chiral BOROX salt, which activates aldehydes toward an asymmetric three‐component Ugi reaction [112].