3 research outputs found
Catalyst-Substrate Helical Character Matching Determines the Enantioselectivity in the Ishihara-Type Iodoarenes Catalyzed Asymmetric Kita-Dearomative Spirolactonization
Catalyst design has traditionally focused on rigid structural
elements
to prevent conformational flexibility. Ishihara’s elegant design
of conformationally flexible C2-symmetric
iodoarenes, a new class of privileged organocatalysts, for the catalytic
asymmetric dearomatization (CADA) of naphthols is a notable exception.
Despite the widespread use of the Ishihara catalysts for CADAs, the
reaction mechanism remains the subject of debate, and the mode of
asymmetric induction has not been well established. Here, we report
an in-depth computational investigation of three possible mechanisms
in the literature. Our results, however, reveal that this reaction
is best rationalized by a fourth mechanism called “proton-transfer-coupled-dearomatization
(PTCD)”, which is predicted to be strongly favored over other
competing pathways. The PTCD mechanism is consistent with a control
experiment and further validated by applying it to rationalize the
enantioselectivities. Oxidation of the flexible I(I) catalyst to catalytic
active I(III) species induces a defined C2-symmetric helical chiral environment with a delicate balance between
flexibility and rigidity. A match/mismatch effect between the active
catalyst and the substrate’s helical shape in the dearomatization
transition states was observed. The helical shape match allows the
active catalyst to adapt its conformation to maximize attractive noncovalent
interactions, including I(III)···O halogen bond, N–H···O
hydrogen bond, and π···π stacking, to stabilize
the favored transition state. A stereochemical model capable of rationalizing
the effect of catalyst structural variation on the enantioselectivities
is developed. The present study enriches our understanding of how
flexible catalysts achieve high stereoinduction and may serve as an
inspiration for the future exploration of conformational flexibility
for new catalyst designs
Asymmetric Mannich Reaction of Isatin-Based Ketimines with α‑DiazoÂmethylÂphosphonates Catalyzed by Chiral Silver Phosphate
An
efficient asymmetric Mannich reaction of isatin-based ketimines
with α-diazomethylÂphosphonates has been developed using
a chiral binaphthanol-derived silver phosphate as the catalyst. This
reaction allowed the construction of a series of chiral oxindoles
bearing a quaternary stereocenter and amino group at the C3 position
with up to 95% yields and 99% <i>ee</i>. Those products
could be further transformed into promising densely functionalized
compounds by merging of the oxindole and β-aminophosphonate
Asymmetric Mannich Reaction of Isatin-Based Ketimines with α‑DiazoÂmethylÂphosphonates Catalyzed by Chiral Silver Phosphate
An
efficient asymmetric Mannich reaction of isatin-based ketimines
with α-diazomethylÂphosphonates has been developed using
a chiral binaphthanol-derived silver phosphate as the catalyst. This
reaction allowed the construction of a series of chiral oxindoles
bearing a quaternary stereocenter and amino group at the C3 position
with up to 95% yields and 99% <i>ee</i>. Those products
could be further transformed into promising densely functionalized
compounds by merging of the oxindole and β-aminophosphonate