posted on 2017-08-21, 00:00authored byBangaru Bhaskararao, Raghavan B. Sunoj
Recent
examples of asymmetric dual chiral catalysis (ADCC), where
two chiral catalysts are employed under one-pot reaction conditions,
have demonstrated how all stereoisomers of a product could be effectively
accomplished through changes in the catalyst chirality. Insufficient
mechanistic details on the action of two chiral catalysts and molecular
insights into the origin of stereodivergence prompted us to undertake
a comprehensive density functional theory (B3LYP-D3) investigation
on an α-allylation reaction of an aldehyde by using an allyl
alcohol, resulting in two new chiral centers in the product. The structural
and energetic features of the stereocontrolling transition states
helped us delineate how all four product stereoisomers could be accessed
by using suitable combinations of chiral iridium phosphoramide and
diarylprolinol silyl ether in this ADCC reaction. The covalent activation
of the pronucleophile (aldehyde) by the organocatalyst furnishes a
chiral enamine, whereas the action of the transition-metal catalyst
(chiral Ir phosphoramidite, P) on racemic allyl alcohol
gives the Ir-π-allyl phosphoramidite complex [IrCl(P)2(π-allyl)], which serves as the electrophilic
partner. The enantioselectivity is directly controlled by the sense
of axial chirality of the Ir-bound phosphoramidite ligand, which affects
whether an R or S stereocenter would
be generated at the β-carbon of the product. The “recognition/interaction”
between the two chiral catalysts in the diastereocontrolling C–C
bond formation transition states through a series of weak noncovalent
interactions (C–H···π, C–H···O,
C–H···Cl, C–H···F, and
lone pair···π) is identified as playing a pivotal
role in influencing the favorable mode of addition of the si or re face of the chiral enamine to
Ir-π-allyl phosphoramidite (si-si/re-re) and hence controls the chirality at the α-carbon atom of
the developing product.