ENANTIOSELECTIVE SYNTHESIS OF alpha-QUATERNARY MANNICH ADDUCTS BY PALLADIUM-CATALYZED ALLYLIC ALKYLATION

摘要

This invention provides enantioenriched Mannich adducts with quaternary stereogenic centers and novel methods of preparing the compounds. Methods include the 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.

主权项

1. A compound represented by formula (I), or a salt thereof; wherein: R1a and R1b each independently 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), —C(O)O(heteroaralkyl), —S(O)2(aryl), —S(O)2(alkyl), —S(O)2(haloalkyl), —OR14, —SR14, or —NR14R15; R2 and R3 each independently represent hydrogen or substituted or unsubstituted alkyl, aralkyl, aryl, heteroaralkyl, heteroaryl, (cycloalkyl)alkyl, cycloalkyl, (heterocycloalkyl)alkyl, heterocycloalkyl, alkenyl, alkynyl, alkylamino, hydroxyalkyl, alkoxyalkyl, aminoalkyl, or thioalkyl; or wherein R1a and R2 are taken together with the intervening atoms to form an optionally substituted heterocyclic ring; R8, R9, R10, and R11 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, cycloalkyl, heterocycloalkyl, aralkyl, arylalkoxy, heteroaralkyl, (cycloalkyl)alkyl, and (heterocycloalkyl)alkyl; W1 and W2 are each independently selected from alkyl, alkenyl, alkynyl, OR12, SR12, or NR12R13; or W1 and W2, taken together with the intervening atoms, form an optionally substituted heterocycloalkyl, cycloalkyl, heterocycloalkenyl, or cycloalkenyl group; R12 and R13 are independently selected for each occurrence from hydrogen or substituted or unsubstituted alkyl, aralkyl, aryl, heteroaralkyl, heteroaryl, (cycloalkyl)alkyl, cycloalkyl, (heterocycloalkyl)alkyl, heterocycloalkyl, alkenyl, alkynyl, hydroxyalkyl, alkoxyalkyl, aminoalkyl, and thioalkyl; R14 and R15 are independently selected for each occurrence from hydrogen or substituted or unsubstituted alkyl, aralkyl, aryl, heteroaralkyl, heteroaryl, (cycloalkyl)alkyl, cycloalkyl, (heterocycloalkyl)alkyl, heterocycloalkyl, alkenyl, and alkynyl.