A Highly Enantio- and Diastereoselective Synthesis of Spirocyclic Dihydroquinolones via Domino Michael Addition-Lactamization of ortho-Quinone Methide Imines

Spirocyclic dihydroquinolones have been obtained with good yields and excellent diastereoselectivity (>20:1 d.r.), and enantioselectivity (up to 99:1 e.r.) from in situ generated ortho-quinone methide imines and cyclic beta-oxo esters. This one-step domino Michael addition-lactamization process features mild reaction conditions, easily accessible starting materials, and products with two adjacent chiral centers one of which is quaternary. Mechanistic studies revealed the in situ generated chiral magnesium phosphate salt rather than the free phosphoric acid to be the more reactive catalyst for this reaction.