Enantioselective synthesis of dialkylated n,o-heterocycles by palladium-catalyzed allylic alkylation

A compound represented by formula (II),

• or a tautomer and/or salt thereof, wherein:
• R1 represents hydrogen or optionally substituted alkyl, cycloalkyl, (cycloalkyl)alkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, alkenyl, alkynyl, —C(O)alkyl, —C(O)aryl, —C(O)aralkyl, —C(O)heteroaryl, —C(O)heteroaralkyl, —C(O)O(alkyl), —C(O)O(aryl), C(O)O(aralkyl), —C(O)O(heteroaryl), or —C(O)O(heteroaralkyl);
• or
• R2 represents hydrogen or substituted or unsubstituted alkyl, aralkyl, aryl, heteroaralkyl, heteroaryl, alkenyl, alkynyl, or halo;
• R3, R4, R5, and R6 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;
• W2, and W3 are independently selected for each occurrence from CR11R12, O, and S;
• 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;
• wherein any occurrence of may optionally combine with any second occurrence of or an occurrence of R12, along with the carbons to which they are attached, to form an optionally substituted 3-8 membered ring;
• and
• n is an integer from 0-3;
• wherein the compound is not

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 represents hydrogen or optionally substituted alkyl, cycloalkyl, (cycloalkyl)alkyl, aryl, aralkyl, heteroaryl, heteroaralkyl, alkenyl, alkynyl, —C(O)alkyl, —C(O)aryl, —C(O)aralkyl, —C(O)heteroaryl, —C(O)heteroaralkyl, —C(O)O(alkyl), —C(O)O(aryl), C(O)O(aralkyl), —C(O)O(heteroaryl), or —C(O)O(heteroaralkyl);
• or
• R2 represents hydrogen or substituted or unsubstituted alkyl, aralkyl, aryl, heteroaralkyl, heteroaryl, alkenyl, alkynyl, or halo;
• R3, R4, R5, R6, R7, R8, R9, and R10 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;
• W1, W2, and W3 are independently selected for each occurrence from CR11R12, O, and S;
• 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;
• wherein any occurrence of may optionally combine with any second occurrence of or an occurrence of R12, along with the carbons to which they are attached, to form an optionally substituted 3-8 membered ring;
• and
• n is an integer from 0-3;
• wherein the compound of formula (I) is not