Asymmetric Mannich reaction between (S)-N-(tert-butanesulfinyl)-3,3,3-trifluoroacetaldimine and malonic acid derivatives. Stereodivergent synthesis of (R)- and (S)-3-amino-4,4,4-trifluorobutanoic acids.
Inorganic as well as organic base catalysis was found to be effective for diastereoselective Mannich additions of malonic acid derivatives to (SS)-N-(tert-butanesulfinyl)-3,3,3-trifluoroacetaldimine. In the presence of catalytic amounts of inorganic bases, n-BuLi or DMAP, the reaction gives the corresponding (R,SS)-β-aminomalonates in good yield and with diastereoselectivity up to 9/1 dr. In contrast, phosphazene bases favour the formation of the (S,SS)-diastereomer with selectivities as high as 99/1. Simple choosing of an appropriate base catalyst for the Mannich addition reaction allowed us to obtain enantiomerically pure (R)- or (S)-configured 3-amino-4,4,4-trifluorobutanoic acids after hydrolysis and decarboxylation of the corresponding β-aminomalonates.
Department of Frontier Materials, Graduate School of Engineering, Nagoya Institute of Technology, Gokiso, Showa-ku, Nagoya 466-8555, Japan. nozshiba@nitech.ac.jp.
Norio
N
Shibata
Takayuki
T
Nishimine
Naoyuki
N
Shibata
Etsuko
E
Tokunaga
Kosuke
K
Kawada
Takumi
T
Kagawa
José Luis
JL
Aceña
Alexander E
AE
Sorochinsky
Vadim A
VA
Soloshonok
D002087:Butyrates / Q000138:chemical synthesis* / Q000737:chemistry; D006845:Hydrocarbons, Fluorinated / Q000138:chemical synthesis* / Q000737:chemistry; D008314:Malonates / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism; D013452:Sulfonium Compounds / Q000737:chemistry*
C000592183:(S)-N-(tert-butanesulfinyl)-3,3,3-trifluoroacetaldimine; C000592184:3-amino-4,4,4-trifluorobutanoic acid; D002087:Butyrates; D006845:Hydrocarbons, Fluorinated; D008314:Malonates; D013452:Sulfonium Compounds; C030290:malonic acid