506436-07-3Relevant academic research and scientific papers
Carbocyclic α,β-diamino acids: Asymmetric Strecker synthesis of stereomeric 1,2-diaminocyclohexanecarboxylic acids
Pai Fondekar, Kamalesh P.,Volk, Franz-J.,Khaliq-uz-Zaman,Bisel, Philippe,Frahm, August W.
, p. 2241 - 2249 (2007/10/03)
Asymmetric syntheses of trans-(R,R)- and (S,S)-1,2-diaminocyclohexanecarboxylic acids have been achieved with ee >99% while the respective cis-(R,S)- and (S,R)-stereoisomers were obtained as 1-amino-2-benzoylaminocyclohexanecarboxylic acids. The underlying second generation asymmetric synthesis proceeds via Strecker reaction with commercially available (R)- and (S)-1-phenylethylamine (1-PEA) as chiral auxiliaries, TMSCN as cyanide source and racemic 2-benzoylaminocyclohexanone. The key stereodifferentiating step of the cyanide addition to the chiral ketimine intermediates has been studied under the influence of protic and aprotic solvents. Hydrolysis of the nitriles to the carboxamides with conc. H2SO4 yielded dramatic changes in the product composition as a function of temperature and time. Hydrolysis of both the attendant amido groups are concomitant processes in case of the trans-configured carboxamides while the cis-stereoisomers undergo selective carboxamide hydrolysis, with the benzoyl protecting group remaining intact, leading to orthogonally protected α,β-diamino acids. The absolute configurations of the amino acids and their intermediates have been assigned based on detailed NMR spectroscopic analysis and X-ray data.
