Catalysis of 3-pyrrolidinecarboxylic acid and related pyrrolidine derivatives in enantioselective anti-Mannich-type reactions: importance of the 3-acid group on pyrrolidine for stereocontrol.
The development of enantioselective anti-selective Mannich-type reactions of aldehydes and ketones with imines catalyzed by 3-pyrrolidinecarboxylic acid and related pyrrolidine derivatives is reported in detail. Both (3R,5R)-5-methyl-3-pyrrolidinecarboxylic acid and (R)-3-pyrrolidinecarboxylic acid efficiently catalyzed the reactions of aldehydes with alpha-imino esters under mild conditions and afforded anti-Mannich products with high diastereo- and enantioselectivities (anti/syn up to 99:1, up to >99% ee). For the reactions of ketones with alpha-imino esters, (R)-3-pyrrolidinecarboxylic acid was an efficient catalyst (anti/syn up to >99:1, up to 99% ee). Evaluation of a series of pyrrolidine-based catalysts indicated that the acid group at the beta-position of the pyrrolidine ring of the catalyst played an important role in forwarding the carbon-carbon bond formation and in directing anti-selectivity and enantioselectivity.
Zhang
Haile
H
The Skaggs Institute for Chemical Biology and the Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Mitsumori
Susumu
S
Utsumi
Naoto
N
Imai
Masanori
M
Garcia-Delgado
Noemi
N
Mifsud
Maria
M
Albertshofer
Klaus
K
Cheong
Paul Ha-Yeon
PH
Houk
K N
KN
Tanaka
Fujie
F
Barbas
Carlos F
CF
D000447:Aldehydes / Q000737:chemistry*; D002384:Catalysis; D007097:Imines / Q000737:chemistry*; D007659:Ketones / Q000737:chemistry*; D015394:Molecular Structure; D011392:Proline / Q000031:analogs & derivatives* / Q000737:chemistry; D011759:Pyrrolidines / Q000737:chemistry*; D013237:Stereoisomerism
C526607:5-methyl-3-pyrrolidinecarboxylic acid; D000447:Aldehydes; D007097:Imines; D007659:Ketones; D011759:Pyrrolidines; D011392:Proline; C032519:pyrrolidine; C072401:beta-proline