ABSTRACT
The first organocatalysed enantioselective [1,3]-sigmatropic O- to N-rearrangement reactions are presented. The reactions take place under regio- and enantioselective control, and are catalysed by cinchona alkaloids. Two reactions have been developed the first one is the rearrangement of imidates to amides, while the other rearrangement occurs from carbamates to amines via a decarboxylation. Both transformations give nitrogen protected beta-amino acid derivatives as the product. These novel asymmetric organocatalysed [1,3]-sigmatropic O- to N-rearrangement reactions provide a reliable and efficient synthetic method for obtaining enantioenriched beta-amino acid derivates in good yield from racemic starting materials.
Subject(s)
Amino Acids/chemical synthesis , Chemistry, Organic/methods , Cinchona Alkaloids/chemistry , Organometallic Compounds/chemistry , Amides/chemistry , Amines/chemistry , Carbamates/chemistry , Catalysis , Decarboxylation , Imides/chemistry , Models, Chemical , Nitrogen/chemistry , Oxygen/chemistry , StereoisomerismABSTRACT
A new concept in organocatalysis is presented, the direct asymmetric gamma-functionalization of alpha,beta-unsaturated aldehydes. We disclose that secondary amines can invert the usual reactivity of alpha,beta-unsaturated aldehydes, enabling a direct gamma-amination of the carbonyl compound using azodicarboxylates as the electrophilic nitrogen-source. The scope of the reaction is demonstrated for the enantioselective gamma-amination of different alpha,beta-unsaturated aldehydes, giving the products in moderate to good yields and with high enantioselectivities up to 93% ee. Experimental investigations and DFT calculations indicate that the reaction might proceed as a hetero-Diels-Alder cycloaddition reaction. Such a mechanism can explain the "unexpected" stereochemical outcome of the reaction.
ABSTRACT
A new class of 6'-hydroxy cinchona alkaloids, with a non-biaryl atropisomeric functionalisation at position 5' of the quinoline core can be prepared by an easy amination procedure. These are the first derivatives for which the principle of atropisomerism is engrafted in the classical core of the cinchona alkaloids. The aminated cinchona alkaloids are effective organocatalysts for the Michael addition of beta-keto esters to acrolein and methyl vinyl ketone, in up to 93 % ee (ee=enantiomeric excess), as well as for the asymmetric Friedel-Crafts amination of a variety of 2-naphthols, permitting the preparation of the latter in up to 98 % ee. The aminated 8-amino-2-naphthol itself is the first chiral organocatalyst based on non-biaryl atropisomerism. The two enantiomers of this chiral primary amine can be used for the direct alpha-fluorination of alpha-branched aldehydes. The fluorinated compounds can thereby be accessed in up to 90 % ee.
