US EPA

7462969 

Journal Article 

Asymmetric Synthesis of Amino-Bis-Pyrazolone Derivatives via an Organocatalytic Mannich Reaction 

Chauhan, P; Mahajan, S; Kaya, U; Peuronen, A; Rissanen, K; Enders, D 

2017 

Yes 

Journal of Organic Chemistry
ISSN: 0022-3263
EISSN: 1520-6904 

American Chemical Society 

82 

13 

7050-7058 

English 

10.1021/acs.joc.7b01113 

A new series of N-Boc ketimines derived from pyrazolin-5-ones have been used as electrophiles in asymmetric Mannich reactions with pyrazolones. The amino-bis-pyrazolone products are obtained in excellent yields and stereoselectivities by employing a very low loading of 1 mol % of a bifunctional squaramide organocatalyst. Depending on the substitution at position 4 of the pyrazolones, the new protocol allows for the generation of one or two tetrasubstituted stereocenters, including a one-pot version combing the Mannich reaction with a base-mediated halogenation. © 2017 American Chemical Society. 

Chemistry; Organic compounds; Asymmetric synthesis; Bi-functional; Electrophiles; Mannich reactions; New protocol; Organocatalysts; Organocatalytic; Stereocenters; Chemical reactions; 1 (4 chlorophenyl) 3 methyl 1h pyrazole 4,5 dione; 1 (4 methylphenyl) 3 methyl 1h pyrazole 4,5 dione; 1,3 diphenyl 1h pyrazole 4,5 dione; 2 (4 chlorophenyl) 5 methyl 4 (phenylimino) 2,4 dihydro 3h pyrazol 3 one; 2,5 diphenyl 4 (phenylimino) 2,4 dihydro 3h pyrazol 3 one; 3 ethyl 1 phenyl 1h pyrazole 4,5 dione; 3 isopropyl 1 phenyl 1h pyrazole 4,5 dione; 3 methyl 1 phenyl 1h pyrazole 4,5 dione; 5 (tert butyl) 2 phenyl 4 (phenylimino) 2,4 dihydro 3h pyrazol 3 one; 5 ethyl 2 phenyl 4 (phenylimino) 2,4 dihydro 3h pyrazol 3 one; 5 isopropyl 2 phenyl 4 (phenylimino) 2,4 dihydro 3h pyrazol 3 one; 5 methyl 2 phenyl 4 (phenylimino) 2,4 dihydro 3h pyrazol 3 one; 5 methyl 4 (phenylimino) 2 (4 tolyl) 2,4 dihydro 3h pyrazol 3 one; pyrazolone derivative; tert butyl (3 ethyl 5 oxo 1 phenyl 1,5 dihydro 4h pyrazol 4 ylidene)carbamate; tert butyl (3 isopropyl 5 oxo 1 phenyl 1,5 dihydro 4h pyrazol 4 ylidene)carbamate; tert butyl (3 methyl 5 oxo 1 phenyl 1,5 dihydro 4h pyrazol 4 ylidene)carbamate; tert butyl (3 tert butyl 5 oxo 1 phenyl 1,5 dihydro 4h pyrazol 4 ylidene)carbamate; tert butyl [1 (2 chlorophenyl) 5 hydroxy 3,3' dimethyl 5' oxo 1' phenyl 1',5' dihydro 1h,4'h (4,4' bipyrazol) 4' yl]carbamate; tert butyl [1 (4 chlorophenyl) 3 methyl 5 oxo 1,5 dihydro 4h pyrazol 4 ylidene]carbamate; tert butyl [1 (4 chlorophenyl) 5 hydroxy 3,3' dimethyl 5' oxo 1' phenyl 1',5' dihydro 1h,4'h (4,4' bipyrazol) 4' yl]carbamate; tert butyl [1 (4 methylphenyl) 3 methyl 5 oxo 1,5 dihydro 4h pyrazol 4 ylidene]carbamate; tert butyl [3 ethyl 5 hydroxy 3' methyl 5' oxo 1,1' diphenyl 1',5' dihydro 1h,4'h (4,4' bipyrazol) 4' yl]carbamate; tert butyl [5 hydroxy 1,3,3' trimethyl 5' oxo 1' phenyl 1',5' dihydro 1h,4'h (4,4' bipyrazol) 4' yl]carbamate; tert butyl [5 hydroxy 3 isopropyl 3' methyl 5' oxo 1,1' diphenyl 1',5' dihydro 1h,4'h (4,4' bipyrazol) 4' yl]carbamate; tert butyl [5 hydroxy 3' methyl 5' oxo 1,1' diphenyl 3 propyl 1',5' dihydro 1h,4'h (4,4' bipyrazol) 4' yl]carbamate; tert butyl [5 hydroxy 3,3' dimethyl 5' oxo 1' phenyl 1 (4 tolyl) 1 (4 tolyl) 1',5' dihydro 1h,4'h (4,4' bipyrazol) 4' yl]carbamate; tert butyl [5 hydroxy 3,3' dimethyl 5' oxo 1,1' diphenyl 1',5' dihydro 1h,4'h (4,4' bipyrazol) 4' yl]carbamate; tert butyl [5 oxo 1,3 diphenyl 1h pyrazol 4(5h) ylidene]carbamate; unclassified drug; unindexed drug; acylation; Article; asymmetric synthesis; catalysis; drug synthesis; enantiomeric ratio; enantioselectivity; halogenation; hydrogen bond; low temperature; Mannich reaction; stereoselectivity