Development of High Performance Transition Metal Catalysts for Dehydrative Asymmetric α-Allylation of Carbonyl Compounds

Principal Investigator

Masato KITAMURA (Professor, Graduate School of Pharmaceutical Sciences, Nagoya University)

Outline of the Project

Geuther-Wislicenus alkylation of 1,3-dicarbonyl compounds has been one of the most frequently utilized C–C bond formations in organic synthesis since the discovery in 1863.  Tsuji revolutionized this chemistry to the Pd-catalyzed allylation in 1965, and then Trost reported the first asymmetric version using Kagan's DIOP in 1977.  The reports as well as other pioneering works have spurred the subsequent research on the related chemistry, which mainly utilizes various chiral phosphine–Pd complexes and others including Mo, Ru, Rh, W, and Ir complexes.  Coupled with the high synthetic utility of "allyl group," the asymmetric Tsuji-Trost reaction has realized the synthesis of various natural products and has made one of core parts of organic synthesis together with other important asymmetric catalyses including Sharpless oxidation and Noyori reduction.  Only the disadvantage is, however, that the enolate formation using a base is required for the reaction with activated allylic alcohols such as allyl halides and esters.  After enhancing the reaction potential, the C–C bond must be formed by the liberation of very stable salt.  Ideal is the direct C–C bond formation from 1,3-dicarbonyl compounds and allylic alcohols without any stoichiometric activation.  Water is only the coproduct.  The dehydrative process should be advantageous from many viewpoints including environmental benignity, energy and resource saving, atom and step economy, safety, and operational simplicity.  The aim of this project is to develop chiral transition metal complexes realizing such an ideal process with high reactivity, selectivity, and productivity.  The chances are based on i) our  own leading concept "redox-mediated donor-acceptor bifunctional catalyst  (RDACat)," ii) synergetic effect of  soft transition metal and hard proton, iii) characteristics of new chiral sp2N bidentate ligand Naph-diPIM-dioxo-R (2,2,13,13-tetraalkyl-3a,11a,14a,16b-tetrahydrobis(1,3-dioxolano[4’,5’:3,4]pyrrolo)[1,2-a :1’,2’-a]naphtho[1,2- d :8,7-d’]diimidazole) that are  highly s donative, near 90° bite angle, high rigidity and planarity, and clear chiral circumstance, and iv) characteristics of cyclopentadienyl (Cp) group that are high electro-donicity, fac specificity, and metastability via h5-h3-h1 equilibrium.  Development of the new asymmetric catalysts for intermolecular dehydrative a-allylation of activated carbonyl compounds such as Meldrum's acid follows a) extension to the intramolecular version, b) inter- and intramolecular a-allyllation of unactivated carbonyl compounds, c) dynamic kinetic asymmetric transformation (DKAT) controlling two consecutive stereogenic centers, d) DKAT-based synthesis of stephacidin A, and e) mechanistic study.


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