Toolbox Approach to the Search for Effective Ligands for Catalytic Asymmetric Cr-Mediated Coupling Reactions

Abstract

Chromium catalysts derived from chiral sulfonamides represented by A effect the couplings of aldehydes with vinyl, allyl, or alkyl halides. With three distinct sites for structural modification, A affords access to a structurally diverse pool of chiral sulfonamides. The Cr catalysts derived from these sulfonamides exhibit a broad range of catalyst-substrate matching profiles. A strategy is presented to search for a satisfactory chiral sulfonamide for a given substrate. In order to demonstrate the generality and effectiveness of this approach, five diverse C-C bond-forming cases have been selected from the halichondrin synthesis. For each of the cases, two ligands have been deliberately searched for, to induce the formation of (R)- and (S)-alcohols, respectively, at the arbitrarily chosen efficiency level of ">or=80% yield with >or=20:1 stereoselectivity in the presence of <or=20 mol % of a Cr catalyst". For 9 out of the 10 cases studied, a satisfactory catalyst has been found within this pool of sulfonamides. Even for the remaining case, a Cr catalyst inducing stereoselectivity up to 8:1 has been identified.

Acyclic Quaternary Carbon Stereocenters via Enantioselective Transition Metal Catalysis

“…97 This work takes advantage of Fürstner’s 1996 report on the chromium-catalyzed Nozaki-Hiyama-Kishi reaction mediated by stoichiometric manganese metal, 98 along with chiral ligand XXVIII previously developed by Kishi. 99 One equivalent of ZrCp 2 Cl 2 , a highly mass-intensive reagent, and one equivalent of cesium iodide were required to improve catalyst turnover and reaction rate. Although good levels of anti -diastereo- and enantioselectivity were observed, the use of multiple stoichiometric metallic reagents and manganese metal diminish the appeal of this method, especially given the earlier disclosure of related alcohol-allene couplings that provide identical products with complete atom-efficiency.…”

Synergistic cytotoxicity caused by forming a complex of copper and 2,9-dimethyl-1,10-phenanthroline in cultured vascular endothelial cells

“…The DMP complexes with zinc (Zn-DMP), manganese (Mn-DMP), iron (Fe-DMP), cobalt (Co-DMP), nickel (Ni-DMP), copper (Cu-DMP), cadmium (Cd-DMP), mercury (Hg-DMP), and lead (Pb-DMP) were synthesized as described previously (Wang, 2009;Preston et al, 1968;Shen and Lush, 2010;Torbati et al, 2010;Das et al, 2013;Guo et al, 2009;Xia et al, 2011;Davies and Loose, 1976;Warad et al, 2011;Warad et al, 2013;Morsali et al, 2004;Hara et al, 2016) with some modifications, and identified by the element analysis.…”

Chromium(II)-catalyzed enantioselective arylation of ketones

“…Since the first example of enantioselective allylation of aldehydes catalyzed by a Cr(II)–salen complex in 1999 by Cozzi and co-workers [12], several elegant catalytic enantioselective allylation and propargylation reactions have been developed by the groups of Nakada [13–14], Berkessel [15], Kishi [16], Sigman [17], Yamamoto [18], Guiry [19], Chen [20], Gade [21], White [22], and Zhang [23–25], respectively. The alkenylation and alkylation reactions were mainly explored by the Kishi group [26–30], and they established a toolbox approach to search for the specific ligand with a given substrate in the Cr-catalyzed process [28]. They successfully applied the method to the natural product total synthesis like halichondrin B and norhalichondrin B, and in the subsequent pharmaceutical study, finally leading to the discovery of the anticancer drug Eribulin [31–35].…”