Synthesis of chiral enaminones, their derivatives, and bioactivity studies thereof

A method for the preparation of a compound of formula (I):

• comprising treating a compound of formula (II):
• with a transition metal catalyst under alkylation conditions, wherein, as valence and stability permit,
• R1 and R2 are independently hydrogen or optionally substituted alkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, alkenyl, or alkynyl;
• or
• R1 and R2 are taken together to form an optionally substituted heterocyclic ring;
• R3 is substituted or unsubstituted hydrogen, alkyl, aralkyl, aryl, heteroaralkyl, heteroaryl, alkenyl, alkynyl, or halo;
• R4 is hydrogen, halogen, alkyl, aralkyl, aryl, heteroaralkyl, heteroaryl, alkenyl, or alkynyl;
• R5, R6, R7, R8, R9, R10, R11, and R12 are independently selected for each occurrence from hydrogen, hydroxyl, halogen, nitro, alkyl, alkenyl, alkynyl, cyano, carboxyl, sulfate, amino, alkoxy, alkylamino, alkylthio, hydroxyalkyl, alkoxyalkyl, aminoalkyl, thioalkyl, ether, thioether, ester, amide, thioester, carbonate, carbamate, urea, sulfonate, sulfone, sulfoxide, sulfonamide, acyl, acyloxy, acylamino, aryl, heteroaryl, carbocyclyl, heterocyclyl, aralkyl, arylalkoxy, heteroaralkyl, carbocyclylalkyl, and heterocyclylalkyl;
• W is CR13R13, O, S, or NR14;
• R13 is selected, independently for each occurrence, from hydrogen, hydroxyl, halogen, nitro, alkyl, alkenyl, alkynyl, cyano, carboxyl, sulfate, amino, alkoxy, alkylamino, alkylthio, hydroxyalkyl, alkoxyalkyl, aminoalkyl, thioalkyl, ether, thioether, ester, amide, thioester, carbonate, carbamate, urea, sulfonate, sulfone, sulfoxide, sulfonamide, acyl, acyloxy, acylamino, aryl, heteroaryl, carbocyclyl, heterocyclyl, aralkyl, arylalkoxy, heteroaralkyl, carbocyclylalkyl, and heterocyclylalkyl;
• R14 is independently selected for each occurrence from hydrogen, alkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, alkenyl, or alkynyl;
• wherein R2 and R4 may combine with the atoms to which they are attached to form an optionally substituted 4-9 membered heterocyclic ring, R4 and an occurrence of R13 may combine with the carbons to which they are attached to form an optionally substituted 3-8 membered ring, R4 and an occurrence of R14 may combine with the atoms to which they are attached to form an optionally substituted 4-8 membered heterocyclic ring, two occurrences of R13 may combine with the carbons to which they are attached to form a 3-8 membered ring, or an occurrence of R13 and an occurrence of R14 may combine with the atoms to which they are attached to form an optionally substituted 4-8 membered heterocyclic ring;
• and
• n is an integer from 1-4.