Asymmetric Dual Chiral Catalysis using Iridium Phosphoramidites and Diarylprolinol Silyl Ethers: Insights into Stereodivergence
journal contributionposted on 2017-08-21, 00:00 authored by Bangaru 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.
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Ir-bound phosphoramidite ligandIr -π-allyl phosphoramiditediarylprolinol silyl etherstereocontrolling transition statesα- allylation reactionchiral catalystsone-pot reaction conditionschiral iridium phosphoramidechiral Ir phosphoramiditeDiarylprolinol Silyl EthersB 3LYP investigationchiral enamineracemic allyl alcoholADCCα- carbon atom