80970-09-8Relevant articles and documents
Regioselective hydration and deprotection of chiral, dissymmetric iminodinitriles in the scope of an asymmetric strecker strategy
Rossi, Jean-Christophe,Marull, Marc,Boiteau, Laurent,Taillades, Jacques
, p. 662 - 668 (2007/10/03)
The controlled, selective decomposition of dissymmetric iminodinitriles (DIDN) of formula RCH(CN)-NH-C(CN)R′R″ (considered as N-protected alpha-aminonitriles), is a critical issue for an original asymmetric Strecker strategy previously outlined by us for the enantioselective synthesis of amino acids. This strategy, derived from Harada's work, involves a double sequence of (i) stereoselective Strecker condensation of a chiral ketone R′R″CO with NH3 and HCN, followed by (ii) stereoselective Strecker condensation with an aldehyde RCHO and HCN, then (iii) regioselective retro-Strecker decomposition of the DIDN intermediate to release the target alpha-aminonitrile. In addition to the use of quite simple, cheap cyclic ketones (e.g. carvone derivatives) as chiral auxiliaries, another great advantage of this strategy is that step (iii) enables the recovery of the chiral ketone and hence its reuse. While our previous investigations on step (iii) under various conditions, either preceded or followed by the hydration of the secondary nitrile group RH(CN)- into an amide, had shown insufficient selectivity, we succeeded in the regioselective hydration of the secondary nitrile of DIDN without significant racemisation, by using a large excess of hydrogen peroxide in methanolic/aqueous ammonia (pH 12.5) at low temperature. The resulting imino nitrile/amide compound was then classically decomposed in acidic medium through a retro-Strecker reaction, affording the chiral alpha-amino amide. Alternately, the regioselective retro-Strecker decomposition of the tertiary moiety of the DIDN was achieved by reaction with silver cation in aqueous nitric acid, also without significant racemisation, thus establishing an original, enantioselective synthesis of alpha-aminonitriles. In both reactions, the chiral ketonic auxiliary resulting from DIDN decomposition was recovered in good yields. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
