Bifuctional Amino-Squaramides Catalyzed Asymmetric Spiroannulation Cascades with Aliphatic β,γ-Unsaturated α-Keto Esters: Controlling an Aldehyde Enolate

A quinidine-derived squaramide Ib catalyzed
cyclization
reaction of β-oxo aldehydes 1 and aliphatic or
aromatic β,γ-unsaturated α-keto ester 2 is described. Using cyclic aldehyde substrates, this procedure provided
a promising approach to a variety of spiro-3,4-dihydropyrans bearing
three continuous quaternary and tertiary stereocenters in moderate
to good yield with high stereoselectivities. Substituents on the nitrogen
atoms of the squaramide moiety of the catalyst proved crucial to the
reaction outcome. The stereochemistry of the three newly formed chiral
centers (trans-selective) of the major product indicates
a Micheal addition/hemiacetalization domino sequence for the present
annulations.