Premium
Herstellung von ( R,R )‐ oder ( S,S )‐2‐Amino‐3‐hydroxycarbonsäuren ( allo ‐Threonin‐Analoge) durch Acylierung/Reduktion von 2‐ t ‐Butyl‐3‐methyl‐4‐oxoimidazolidin‐1‐carbonsäure‐ t ‐butylester (Boc‐BMI)
Author(s) -
Blank Stefan,
Seebach Dieter
Publication year - 1993
Publication title -
liebigs annalen der chemie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0170-2041
DOI - 10.1002/jlac.1993199301140
Subject(s) - chemistry , acylation , stereochemistry , epimer , threonine , hydrolysis , derivative (finance) , stereoselectivity , medicinal chemistry , serine , organic chemistry , catalysis , enzyme , financial economics , economics
Preparation of ( R,R )‐ or ( S,S )‐2‐Amino‐3‐hydroxycarboxylic Acids ( allo ‐Threonine Analogs) by Acylation/Reduction of t ‐Butyl 2‐ t ‐Butyl‐3‐methyl‐4‐oxoimidazolidine‐1‐carboxylate (Boc‐BMI) While there are numerous methods of preparing threonine analogs by aldol additions of chiral glycine derivatives to aldehydes, only few general routes leading to the epimers with C,C‐bond formation are presently available. This paper describes the acylation of the title compound 1 with acyl chlorides (→ trans products 2 – 9 ), the subsequent reduction with LiBHEt 3 in THF (→ hydroxyalkylated BMI derivatives 10 – 14 ), and acidic hydrolysis to the free allo ‐threonines 18 – 22 . The first two steps are totally stereoselective (by NMR analysis), and the overall yields from BocBMI are in the order of 30–60%. Only allo ‐threonines without branching in the γ‐position are accessible by this method. In one case we have also applied this sequence of steps to prepare an α‐branched allo ‐threonine derivative 26 . – The 5‐acyl‐BocBMI derivatives 2 – 9 are remarkably stable to epimerization at the center between the two carbonyl groups. Possible reasons for this are discussed and are partially supported by an X‐ray crystal structure analysis of the phenacetyl derivative 6 .