Enantioselective Synthesis of Cyclohexadienone Containing Spiroketals via DyKat Ketalization/oxa-Michael Addition Cascade

An
oxidative dearomatization of phenol followed by a dynamic kinetic
(DyKat) ketalization/oxa-Michael addition cascade using cinchona alkaloid-based
chiral bifunctional amino-squaramide catalysts is reported. A broad
array of sterically hindered [5,5]-spiroketals attached to a cyclohexadienone
moiety in spiro-fashion is synthesized in an enantiopure form. Further,
the methodology was optimized and extended to the corresponding benzannulated
[5,5]-spiroketals attached to a cyclohexadienone moiety in spiro-fashion.
In general, good yields and excellent diastereoselectivies and enantioselectivities
(up to 20:1 dr and up to 99% ee) were obtained.