The Mannich reaction of various 5-substituted and N-acyl substituted chiral hydantoins with a series of aldimines smoothly occurred with full stereochemical control. These Mannich adducts have been cleaved by alcoholysis to afford several synthetically useful chiral building blocks like β-amino esters and β-lactams in good yields and in enantiopure form.

The synthesis of high loading and recyclable pentaerythritol supported imidazolidin-4-one catalyst I and its application in enantioselective Diels–Alder reactions of cyclopentadiene and α,β-unsaturated aldehydes with high performance were described. Especially noteworthy, the pentaerythritol supported imidazolidin-4-one with high loading capacity can be recovered by simple precipitation and filtration, and recycled for up to four runs without observing significant decrease in catalytic activity.

The Mannich reaction of titanium enolates of a chiral hydantoin with various aldimines smoothly occurred in good yields and with high anti-diastereoselectivity. The Mannich adducts can be readily cleaved by alcoholysis to afford several β-amino ester derivatives in good yields and in almost enantiomerically pure form.(S)-5-Isopropyl-3-phenyl-1-propionylhydantoinC15H18N2O3[α]D20=+10.4 (c 6.33, CH2Cl2)Absolute configuration: (S)Source of chirality: (S)-5-Isopropyl-3-phenylhydantoin(5S,2′R,3′S)-5-Isopropyl-3-phenyl-1-[2′-methyl-3′-(p-methoxyphenylamino)-3′-phenyl-propionyl]hydantoinC29H31N3O4[α]D20=-21.3 (c 1.04, CH2Cl2)Absolute configuration: (5S,2′R,3′S)Source of chirality: hydantoin induced Mannich reaction(5S,2′R,3′S)-5-Isopropyl-3-phenyl-1-[2′-methyl-3′-(p-methoxyphenylamino)-3′-(p-chloro-phenyl)-propionyl]hydantoinC29H30ClN3O4[α]D20=-24.2 (c 1.11, CH2Cl2)Absolute configuration: (5S,2′R,3′S)Source of chirality: hydantoin induced Mannich reaction(5S,2′R,3′S)-5-Isopropyl-3-phenyl-1-[2′-methyl-3′-(p-methoxyphenylamino)-3′-(m-nitro-phenyl)-propionyl]hydantoinC29H30N4O6[α]D20=-23.5 (c 0.92, CH2Cl2)Absolute configuration: (5S,2′R,3′S)Source of chirality: hydantoin induced Mannich reaction(5S,2′R,3′S)-5-Isopropyl-3-phenyl-1-[2′-methyl-3′-(p-methoxyphenylamino)-3′-(2″,3″-dimethoxyphenyl)-propionyl]hydantoinC31H35N3O6[α]D20=-30.6 (c 1.85, CH2Cl2)Absolute configuration: (5S,2′R,3′S)Source of chirality: hydantoin induced Mannich reaction(5S,2′R,3′S)-5-Isopropyl-3-phenyl-1-[2′-methyl-3′-(p-methoxyphenylamino)-3′-(2″-furyl)-propionyl]hydantoinC27H29N3O5[α]D20=-28.4 (c 0.83, CH2Cl2)Absolute configuration: (5S,2′R,3′S)Source of chirality: hydantoin induced Mannich reaction(5S,2′R,3′S)-5-Isopropyl-3-phenyl-1-[2′-methyl-3′-(p-methoxyphenylamino)-3′-(2″-thienyl)-propionyl]hydantoinC27H29N3O4S[α]D20=-25.9 (c 1.45, CH2Cl2)Absolute configuration: (5S,2′R,3′S)Source of chirality: hydantoin induced Mannich reaction(2R,3S)-Methyl 2-methyl-3-(p-methoxyphenylamino)-3-phenylpropanoateC18H21NO3[α]D20=-50.8 (c 1.02, CH2Cl2)Absolute configuration: (2R,3S)Source of chirality: hydantoin induced Mannich reaction(2R,3S)-Methyl 2-methyl-3-(p-methoxyphenylamino)-3-(p–chloro-phenyl)propanoateC18H20ClNO3[α]D20=-43.1 (c 0.57, CH2Cl2)Absolute configuration: (2R,3S)Source of chirality: hydantoin induced Mannich reaction(2R,3S)-Methyl 2-methyl-3-(p-methoxyphenylamino)-3-(m-nitro-phenyl)propanoateC18H20N2O5[α]D20=-48.2 (c 1.16, CH2Cl2);Absolute configuration: (2R,3S)Source of chirality: hydantoin induced Mannich reaction(2R,3S)-Methyl 2-methyl-3-(p-methoxyphenylamino)-3-(2′,3′-dimethoxyphenyl)propanoateC20H25NO5[α]D20=-53.7 (c 2.20, CH2Cl2)Absolute configuration: (2R,3S)Source of chirality: hydantoin induced Mannich reaction(2R,3S)-Methyl 2-methyl-3-(p-methoxyphenylamino)-3-(2′-furyl)-propanoateC16H19NO4[α]D20=-47.6 (c 1.05, CH2Cl2)Absolute configuration: (2R,3S)Source of chirality: hydantoin induced Mannich reaction(2R,3S)-Methyl 2-methyl-3-(p-methoxyphenylamino)-3-(2′-thienyl)-propanoateC16H19NO3S[α]D20=-45.8 (c 1.10, CH2Cl2)Absolute configuration: (2R,3S)Source of chirality: hydantoin induced Mannich reaction(3R,4S)-1-(4-Methoxyphenyl)-3-methyl-4-phenylazetidin-2-oneC17H17NO2[α]D20=-46.1 (c 0.89, CHCl3)Absolute configuration: (3R,4S)Source of chirality: hydantoin induced Mannich reaction

The stereoselective synthesis of the (2R,5S)-2-methyl-5-hexanolide, a sex pheromone of Xylocopa hirutissima, has been achieved in 6 steps and 33% overall yield. The synthesis relies on an asymmetric N-acetyl thiazolidinethione aldol reaction to establish the C5 stereogenic centers. The remaining stereogenic center at C2 was set through a N-propionylprolinol-mediated asymmetric alkylation reaction.(3S)-1-[(S)-4-Benzyl-2-thioxothazolidin-3-yl]-3-hydroxybutan-1-oneC14H17NO2S2[α]D25=+167.2 (c 1.143, CHCl3)Absolute configuration: (3S,4′S)Source of chirality: Evans Aldol reaction(3S)-1-[(S)-4-Benzyl-2-thioxothazolidin-3-yl]-3-(tert-butyldimethylsilyloxy)butan-1-oneC20H31NO2S2Si[α]D25=+120.2 (c 1.220, CHCl3)Absolute configuration: (3S,4′S)Source of chirality: Evans Aldol reaction(S)-3-(tert-Butyldimethylsilyloxy)-1-butanolC10H24O2Si[α]D25=+24.6 (c 0.906, CHCl3)Absolute configuration: (3S)Source of chirality: Evans Aldol reaction(S)-3-(tert-Butyldimethylsilyloxy)butyl iodideC10H23IOSi[α]D25=+50.2 (c 0.833, CHCl3)Absolute configuration: (3S)Source of chirality: Evans Aldol reaction(2R,5S)-5-(tert-Butyldimethylsilyloxy)-1-[(S)-2-(hydroxymethyl)pyrrolidin-1-yl]-2-methylhexan-1-oneC18H37NO3Si[α]D25=+22.5 (c 0.600, CHCl3)Absolute configuration: (2R,2′S,5S)Source of chirality: asymmetric alkylation(2R,5S)-2-Methyl-5-hexanolideC7H12O2[α]D25=-95.1 (c 0. 427, CHCl3)Absolute configuration: (2R,5S)Source of chirality: asymmetric synthesis