to trisubstituted nitroalkenes catalyzed by cinchona alkaloid‐squaramide 2t (Scheme 3.22) [44]. This transformation constitutes the first example of nucleophilic addition to a trisubstituted nitroalkene followed by the enantioselective protonation.
Scheme 3.22. Enantioselective addition of thioacids to trisubstituted nitroalkenes catalyzed by 2t.
Source: Based on [44].
Liu, Li, and co‐workers developed the enantioselective addition of thiols to in situ generated ortho‐quinone methides 17 (Scheme 3.23) [45]. Cinchona alkaloid‐squaramide 2u was employed as a catalyst and water was used as a solvent. The control experiments suggested that water–oil biphase was crucial to achieve both high yields and high stereoselectivity in this reaction.
Scheme 3.23. Enantioselective addition of thiols to in situ generated ortho‐quinone methides catalyzed by 2u.
Source: Based on [45].
3.2.3. Other Applications
Enantioselective cascade reactions under organocatalysis have emerged as a powerful methodology for the efficient synthesis of complex molecules having multiple stereogenic centers in operationally simple protocols by using readily available precursors [46]. Chiral tertiary amine catalysts have also been utilized in a variety of enantioselective cascade reactions [20a]. Following are some selected examples of such reactions. Wang and co‐workers developed enantioselective Michael/cyclization reaction sequence for the synthesis of spirooxindoles [47]. The reaction of α‐isothiocyanato imides, esters, and lactones with alkylidene oxindoles was promoted by amine‐thiourea catalyst 2v to provide the corresponding spirooxindoles in high yields with high stereoselectivities (Scheme 3.24).
Scheme 3.24. Enantioselective Michael/cyclization reaction sequence catalyzed by 2v. Source: Based on [47].
On the other hand, Connon and Manoni reported the catalytic enantioselective Tamura cyclization of enolizable anhydrides with alkylidene oxindoles, providing a different type of spirooxindoles (Scheme 3.25) [48]. In this reaction, an unusual temperature‐controlled diastereodivergency was observed.
Scheme 3.25. Enantioselective Tamura cyclization catalyzed by 2w.
Source: Based on [48].
The enantioselective formal [3+2] cycloaddition of cyclopropyl ketones with nitroalkenes was developed by Jørgensen and co‐workers (Scheme 3.26) [49]. This reaction would involve the ring‐opening of a cyclopropane moiety, which would occur through the deprotonation of the α‐proton and β‐elimination under the influence of amine‐thiourea catalyst 2x, and the following stereoselective intermolecular/intramolecular addition sequence.
Scheme 3.26. Enantioselective formal [3+2] cycloaddition of cyclopropyl ketones with nitroalkenes catalyzed by 2x.
Source: Based on [49].
Rodriguez, Coquerel, and co‐workers established the enantioselective synthesis of benzazocinones by using cinchona alkaloid‐squaramide catalyst 2c [50]. The reaction involves the Michael addition/four‐atom ring expansion cascade from activated cyclobutanones and ortho‐amino nitro styrene derivatives (Scheme 3.27). The resulting benzazocinone products could be further converted into functionalized glutarimide derivatives by 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU) catalyzed ring contraction.
Scheme 3.27. Enantioselective synthesis of benzazocinones. Source: Based on [50].
As a different type of application of the catalysis, Bressy, Bugant, Rodriguez, and co‐workers developed an enantioselective synthesis of axially chiral 4‐arylpyridine derivatives 19 based on the central‐to‐axial chirality conversion strategy (Scheme 3.28) [51]. In this synthesis, 4‐aryl‐1,4‐dihydropyridines 18 having a central chirality were first prepared through the enantioselective Michael addition of dimedone to chalcone derivatives catalyzed by Takemoto’s catalyst 2a and the treatment of the resulting Michael adducts with ammonium acetate. Then, the intermediates 18 were converted to the corresponding axially chiral 4‐arylpyridines 19 by MnO2‐mediated oxidation with moderate to high conversion percentage (cp = %ee of substrate/%ee of product).
Scheme 3.28. Enantioselective synthesis of axially chiral 4‐arylpyridine derivatives based on the central‐to‐axial chirality conversion strategy.
Source: Based on [51].
Later, the same group achieved, for the first time, the synthesis of enantio‐enriched atropoisomeric furans based on the central‐to‐axial chirality conversion strategy (Scheme 3.29) [52].
Scheme 3.29. Enantioselective synthesis