Recent applications of Cinchona alkaloids and their derivatives as catalysts in metal-free asymmetric synthesis

Highly Efficient “On Water” Catalyst‐Free Nucleophilic Addition Reactions Using Difluoroenoxysilanes: Dramatic Fluorine Effects

“…Therefore, it was possible to use a chiral Lewis base to activate 1 a from the interior of the droplet and cooperate with the hydrogen-bonding interactions at the periphery to realize asymmetric synthesis. Indeed, when (QD) 2 PYR [18] was used, 3 aa was obtained in 73 % yield and 39 % ee. Increasing the loading of (QD) 2 PYR from 10 mol % to 30 mol % resulted in the increase of the ee value of 3 aa from 39 to 53 %, [19] possibly because (QD) 2 PYR was dis-Scheme 2.…”

Development of Chiral Organosuperbase Catalysts Consisting of Two Different Organobase Functionalities

“…In addition, substantial enantioselectivity was detected, which revealed that the newly-developed organosuperbase was indeed able to serve as a chiral Brønsted base catalyst. As a control experiment, the reaction was attempted with achiral bases possessing different basicities (entries [2][3][4]. The use of less basic guanidine (TBD = 1,5,0.…”

“…Conventionally, chiral tertiary amines have been widely employed as chiral Brønsted base catalysts. [2] Recently, chiral uncharged organobases with higher basicity than tertiary amines, such as chiral guanidines, P1phosphazenes, and cyclopentenimines, have also emerged as efficient chiral Brønsted base catalysts. [3][4][5][6] However, the insufficient basicity of these conventional chiral organobases limits the scope of pronucleophiles to highly acidic compounds, such as b-dicarbonyl compounds and nitroalkanes, which restricts the viable molecular transformations that are available under chiral Brønsted base catalysis.…”

“…Alternatively, chiral acyclic organobases with an additional acidic functionality as a substrate recognition site are also common motifs of chiral Brønsted base catalysts (Figure 2 b). [2,5] Such so-called chiral "acid-base" bifunctional catalysts are more readily accessible than cyclic ones with more structural diversity. However, application of this motif to chiral organosuperbases is not feasible because intramolecular quenching of the organosuperbase moiety by the acid functionality would occur to form a zwitterionic species with considerable reduction of the basicity.…”

Organocatalytic Asymmetric Synthesis of Trifluoromethyl‐substituted Diarylpyrrolines: Enantioselective Conjugate Cyanation of β‐Aryl‐β‐trifluoromethyl‐disubstituted Enones

“…N-3,5-Bis(trifluoromethylbenzyl) quinidinium bromide (5 a) was selected as the asymmetric catalyst as it is the best catalyst for the enantioselective asymmetric hydroxylamine enone cascade reaction of 3 a as previously reported. [4,11] We therefore hypothesized that the hydrogen bonding could be hindering the desired conjugate addition, so a variety of OH-protected ether-type cinchona alkaloids were synthesized (see Table S1 in the Supporting Information). The desired conjugate adduct 4 a was obtained only in 22 % yield with 0 % ee (entry 1).…”