Methods for synthesizing substituted tetracycline compounds

A method for synthesizing a 9-substituted tetracycline compound, the method comprising:

• a) reacting a 9-halogenated tetracycline compound with carbon monoxide, a first palladium catalyst, a silane and a base to generate a 9-carboxaldehyde substituted tetracycline compound;
• and
• b) reacting said 9-carboxaldehyde substituted tetracycline compound with a primary or secondary amine under hydrogenolysis or reductive amination conditions to generate said 9-substituted tetracycline compound, or a pharmaceutically acceptable salt or ester thereof.