Primary amine catalysts derived from cinchona alkaloids have emerged as readily available, highly versatile and extremely powerful catalysts in asymmetric synthesis. In particular, they exhibit superior catalytic efficacy for successfully tackling major challenges in a variety of sterically hindered carbonyl compounds, which traditional approaches have not been able to address. This review aims to once again draw attention to this relatively underutilised process by highlighting the recent developments in the application of cinchona-based primary amine catalysts in asymmetric organocatalytic reactions.

Chiral cyclohex-2-enones are important building blocks in synthetic chemistry and the life science industries and much attention has been drawn to the development of efficient and practical methodologies for accessing these enantio-enriched cyclohex-2-enone skeletons. This review describes the impressive progress that has been made in terms of employing new methodologies, suitable reactants as well as more efficient catalyst systems for this important enantioselective transformation. Also, the reaction mechanisms are briefly discussed.

A kind of simple primary amine–thiourea organocatalysts was developed. And their application in asymmetric conjugate addition of ketone to nitroalkene was investigated. In the presence of the new primary amine–thiourea, the conjugate addition of ketone to nitroalkene proceeded smoothly to afford the 1,4-adducts in high yields with good enantioselectivities.

An efficient enantioselective aza-Michael addition of pyrazole to chalcone was established. In the presence of the primary amine derived from cinchona alkaloid and acidic additive, the reactions afforded 1,4-adducts in high yields (up to 98%) with 68–88% ee.1,3-Diphenyl-3-(1H-pyrazol-1-yl)propan-1-oneC18H16N2O[α]D20=+64.3 (c 1.00, CHCl3) 76% eeAbsolute configuration: not known1-Phenyl-3-(1H-pyrazol-1-yl)-3-p-tolylpropan-1-oneC19H18N2O[α]D20=+34.2 (c 1.00, CHCl3) 68% eeAbsolute configuration: not known3-(3-Bromophenyl)-1-phenyl-3-(1H-pyrazol-1-yl)propan-1-oneC18H15N2OBr[α]D20=+56.9 (c 1.00, CHCl3) 82% eeAbsolute configuration: not known1-(3-Methoxyphenyl)-3-phenyl-3-(1H-pyrazol-1-yl)propan-1-oneC19H18N2O2[α]D20=+66.5 (c 1.00 CHCl3) 77% eeAbsolute configuration: not known3-(4-Fluorophenyl)-1-phenyl-3-(1H-pyrazol-1-yl)propan-1-oneC18H15N2OF[α]D20=+58.2 (c 1.00, CHCl3) 72% eeAbsolute configuration: not known3-(4-(Trifluoromethyl)phenyl)-1-phenyl-3-(1H-pyrazol-1-yl)propan-1-oneC19H15N2OF3[α]D20=+60.2 (c 1.00, CHCl3) 84% eeAbsolute configuration: not known3-(4-Bromophenyl)-1-phenyl-3-(1H-pyrazol-1-yl)propan-1-oneC18H15N2OBr[α]D20=+36.0 (c 1.00, CHCl3) 83% eeAbsolute configuration: not known3-(3-Nitrophenyl)-1-phenyl-3-(1H-pyrazol-1-yl)propan-1-oneC18H15N3O3[α]D20=+27.9 (c 0.80, CHCl3) 80% eeAbsolute configuration: not known3-(4-Bromophenyl)-1-(3-chlorophenyl)-3-(1H-pyrazol-1-yl)propan-1-oneC18H14N2OClBr[α]D20=+27.8 (c 1.00, CHCl3) 76% eeAbsolute configuration: not known1-(4-Methoxyphenyl)-3-(1H-pyrazol-1-yl)-3-p-tolylpropan-1-oneC20H20N2O2[α]D20=+32.1 (c 1.00, CHCl3) 83% eeAbsolute configuration: not known3-(4-Methoxyphenyl)-1-phenyl-3-(1H-pyrazol-1-yl)propan-1-oneC19H18N2O2[α]D20=+12.5 (c 1.00, CHCl3) 30% eeAbsolute configuration: not known1-(3-Chlorophenyl)-3-phenyl-3-(1H-pyrazol-1-yl)propan-1-oneC18H15N2OCl[α]D20=+49.0 (c 1.00, CHCl3) 66% eeAbsolute configuration: not known3-(3,5-Dimethyl-1H-pyrazol-1-yl)-1,3-diphenylpropan-1-oneC20H20N2O[α]D20=+124.4 (c 1.00, CHCl3) 72% eeAbsolute configuration: not known

Chiral cyclohex-2-enones are important building blocks in synthetic chemistry and the life science industries and much attention has been drawn to the development of efficient and practical methodologies for accessing these enantio-enriched cyclohex-2-enone skeletons. This review describes the impressive progress that has been made in terms of employing new methodologies, suitable reactants as well as more efficient catalyst systems for this important enantioselective transformation. Also, the reaction mechanisms are briefly discussed.

Primary amine catalysts derived from cinchona alkaloids have emerged as readily available, highly versatile and extremely powerful catalysts in asymmetric synthesis. In particular, they exhibit superior catalytic efficacy for successfully tackling major challenges in a variety of sterically hindered carbonyl compounds, which traditional approaches have not been able to address. This review aims to once again draw attention to this relatively underutilised process by highlighting the recent developments in the application of cinchona-based primary amine catalysts in asymmetric organocatalytic reactions.