Enantioselective Michael Addition To ?,?-Unsaturated Amides And Related Cascade Reactions

In this thesis,organocatalytic enantioselective Michael addition to ?,?-unsaturated amides and its cascade reactions are described.The following three chapters are as follows.Chapter OneThe organocatalytic enantioselective Michael addition and its cascade reactions are briefly summarized.In general,strategies of organocatalytic enantioselective Michael addition can be classified into two types: the first type is covalent catalysis,including proline,primary amines and carbeens;the other is hydrogen bonding catalysis,including chiral thioureas,phosphoric acids,polypeptides and guanidines.In this chapter,we summarize the above catalytic types,respectively.Additionally,we also summarize some representative cascade reactions involving organocatalytic enantioselective Michael addition.Chapter TwoIn this chapter,asymmetric catalytic synthesis of chiral 2,3-allenamides from hydrogen-bond-stabilized enynamides in the presence of quinine-based bifunctional squaramide organocatalysts is described.This protocol forms a variety of chiral 2,3-allenamides in high yields and excellent stereoselectivities,in which the elaborated introduction of intramolecular H-bonds within the N,N-bidentate amide group constitutes one of the keys to this highly enantioselective transformation.The synthetic practicality of this reaction has been demonstrated by the axis-to-center chirality transfer of allenamides to furnish enantiomerically enriched building blocks.Chapter ThreeIn this chapter,a sequential protocol involving organocatalytic enantioselective Michael addition/remote C-H olefination/intramolecular Michael addition has been developed for the asymmetric construction of chiral tetralin derivatives bearing three stereogenic centers from readily accessible 2-aryl N-quinolyl acrylamides,nitromethane and alkenyl iodides.The optimized process utilizes a quinine-based squaramide bifunctional organocatalyst to promote the enantioselective addition of nitromethane to the conjugated amides,which are well-known as inert Michael acceptor.Subsequently,N,N-bidentate amidedirected Pd(II/IV)catalyzed C-H olefination and intramolecular Michael addition generates chiral tetralins in good yields and high enantioselectivities.The practicality of this protocol can be demonstrated by a gram-scale one-pot experiment with no erosion of the stereoselectivity.Further conversion of the resulting tetralins delivers chiral 2-aminotetralin derivatives containing multiple stereocenters,which are important bioactive molecules.