Scheme 4.33. Asymmetric Mukaiyama aldol reaction catalyzed by a highly acidic BINOL‐derived disulfonimide.

      Source: Based on [113].

A variety of stabilized oxocarbenium intermediates has been shown to be compatible with this reaction paradigm. In 2013, the Terada group demonstrated an enantioselective reduction of hydroxy‐pyrans via a pyrylium/TRIP chiral ion‐pair (Scheme 4.34) [115]. A similar pyrylium intermediate was shown to undergo an enantioselective Diels‐Alder via ion‐pairing with a chiral phosphate, followed by rearrangement to an exo‐cyclic ketone [116]. Nonaromatic oxocarbeniums have also been accessed and utilized in chiral‐anion catalysis, as demonstrated by the Nagorny group. In this work, an allyl acetal underwent a Diels‐Alder, via the intermediacy of an allylic oxocarbenium ion‐paired with a chiral phosphate anion [117].

In order to access oxocarbenium intermediates without stabilizing moieties, more acidic chiral acids were required to favor ionization of the substrate. In 2016, the Thiel, De, and List groups developed an oxa‐Pictet‐Spengler reaction, catalyzed by a highly acidic imidodiphosphoric acid (Scheme 4.35) [118]. In 2018, Scheidt demonstrated that a similar oxa‐Pictet‐Spengler reaction could be realized with a less acidic chiral catalyst [119], by introducing exogenous achiral urea to increase the acidity of the catalyst via hydrogen bonding of the phosphate anion. Similarly, a bifunctional catalyst featuring a thiourea moiety to greatly increase the acidity of an intramolecular carboxylic acid was shown to be competent for this reactivity [120].

A potential alternative to the use of stronger chiral acids to access unstabilized oxocarbeniums was demonstrated in 2015 by the Luo group (Scheme 4.36) [121]. In this example, a trityl cation/chiral phosphate salt was shown to activate α‐ketoesters toward asymmetric reactivity with a variety of coupling partners. Numbers of transformations were compatible with this system, such as 1,4‐addition with indoles, Diels‐Alder with cyclopentadiene, and 1,2‐addition with α‐methyl styrene, which occurred in high yields and selectivities.

      4.3.3. Carbocation

A variety of asymmetric intramolecular reactions was developed featuring stabilized carbocations as intermediates. In 2010, the Antilla group demonstrated that chiral phosphoric acids could catalyze the enantioselective semi‐pinacol rearrangement of an indolyl diol via intermediacy of the indolyl cation/chiral phosphate ion‐pair (Scheme 4.37) [122]. A vinylogous variant of this reaction was reported in 2016 by the Zhu group, forming β,γ‐unsaturated ketones in high yields and enantioselectivities [123]. Other intramolecular reactivity was shown in 2018 by the Ariafard and Chan groups, with an enantioselective Nazarov‐type electrocyclization of allylic alcohols, forming chiral indenes and tricyclic compounds in high yields and enantioselectivities [124].

Scheme 4.34. Asymmetric counteranion‐directed catalysis involving stabilized oxocarbenium intermediates.

      Source: Based on [115].

Scheme 4.35. Asymmetric counteranion‐directed catalysis with unstabilized oxocarbenium intermediates.

      Source: Based on [118].

Scheme 4.36. Trityl cation/ chiral phosphate salt activation of α‐ketoesters.

      Source: Based on [121].

Scheme 4.37. Intramolecular asymmetric counteranion‐directed catalysis with carbocation intermediates.

      Source: Based on [122].

Intermolecular transformations utilizing carbocations in conjunction with chiral‐anions have been of recent synthetic interest. In 2017, the Sun group demonstrated an asymmetric intermolecular reaction involving ion‐pairing with carbocations (Scheme 4.38) [125]. In this example, a propargyl alcohol is ionized by protonation/dehydration with N‐triflylphosphoramide catalysts. This intermediate was then shown to undergo nucleophilic attack by 1,3‐diketones and thioacetic acid in high yields and enantioselectivities. Following this, the Peng and Yang groups [126], as well as the Kartika group [127], demonstrated enantioselective intermolecular arylation reactions of allyl alcohols with indoles.

Scheme 4.38. Intermolecular asymmetric counteranion‐directed catalysis with carbocation intermediates.

      Source: Based on [125].

      4.3.4. Miscellaneous

A novel ion‐pairing strategy was demonstrated in 2008 by Toste and coworkers (Scheme 4.39) [128]. In this example, chiral phosphoric acid or silver phosphate salts would convert

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