Nonheme Iron-Catalyzed Enantioselective cis -Dihydroxylation of Aliphatic Acrylates as Mimics of Rieske Dioxygenases

Abstract

Enantioselective cis-dihydroxylation of alkenes represents an ideal route to synthesize enantioenriched syn-2,3-dihydroxy esters that are important structural motifs in numerous biologically and pharmaceutically relevant molecules. Bioinspired nonheme iron-catalyzed enantioselective cis-dihydroxylation meets the requirement of the modern synthetic chemistry from atomic economy, green chemistry and sustainable development perspectives. However, nonheme iron-catalyzed enantioselective cis-dihydroxylation is much underdeveloped because of the formidable challenges of controlling chemo-and enantioselectivities and product selectivity caused from the competitive epoxidation, cis-dihydroxylation and overoxidation reactions.Herein, we disclose a biologically inspired nonheme iron complex-catalyzed enantioselective cisdihydroxylation of multi-substituted acrylates using hydrogen peroxide (H 2 O 2 ) as a terminal oxidant by controlling the non-ligating or weakly ligating counterions of iron(II) complexes; we have demonstrated a dramatic counteranion effect on the enantioselective cis-dihydroxylation of olefins by H 2 O 2 catalyzed by nonheme iron complexes. A range of structurally disparate alkenes are transformed to the corresponding syn-2,3-dihydroxy esters in practically useful yields with exquisite chemo-and enantioselectivities (up to 99% ee).Given the mild and benign nature of this biologically inspired oxidation system and the ubiquity and synthetic utility of enantioenriched syn-2,3-dihydroxy esters in pharmaceuticals candidates and natural products, we

Mononuclear Non-Heme Manganese-Catalyzed Enantioselective cis-Dihydroxylation of Alkenes Modeling Rieske Dioxygenases

“…Based on the H 2 18 O experiments, the possibility of manganese­(III)-hydroperoxide and manganese­(III)-peroxysulfate as the reactive intermediate was ruled out since both manganese­(III)-hydroperoxide and manganese­(III)-peroxysulfate cannot exchange their oxygen atoms with water. This result is completely different from the previous reports on the asymmetric cis -dihydroxylation of olefins by non-heme iron complexes and H 2 O 2 , in which no 18 O-incorporation from H 2 18 O into the cis -dihydroxylation product was observed and the oxygen atoms in the cis -diol product were from the same molecule of H 2 O 2 . The result led the authors to propose an iron­(III)-hydroperoxide as the reactive intermediate …”

“…Then, other reaction parameters such as solvent, temperature, and oxidant loading were examined using C1 as the catalyst (Table , entries 6–15). It is shown that the property of the solvent has a great influence on the catalytic performance toward cis -dihydroxylation (Table , entries 6–10), and methanol afforded the optimal yield and enantioselectivity (Table , entry 6), which is similar to the previous reports on non-heme iron-catalyzed asymmetric cis -dihydroxylation of olefins . More effectively, lowering the reaction temperature was demonstrated to be helpful in improving both the yield and the enantioselectivity (Table , entries 11–13), and 72% yield and 88% ee were obtained when the temperature was lowered to −20 °C (Table , entry 13).…”

“…Excellent examples are naturally occurring Rieske dioxygenases that can perform the enantioselective cis -dihydroxylation of arenes with molecular oxygen (O 2 ) activation, in which both O-atoms of O 2 are incorporated into arenes (or olefins) to produce cis -diol products (Figure A). − Moreover, iron–oxygen species, such as iron­(V)-oxo-hydroxo (HO–Fe V O), iron­(IV)-dihydroxo, iron­(III)-superoxo, and iron­(III)-hydroperoxo, have been invoked as the active oxidant(s) in cis -dihydroxylation of olefinic double bonds by Rieske dioxygenases and non-heme iron model catalysts (Figure A). − Inspired by the structural mononuclear non-heme ferrous center and the mechanistic principles that underlie their function as catalysts for aerobic cis -dihydroxylation of aromatic and olefinic CC double bonds with exquisite stereo- and enantioselectivities, much effort has been devoted to the development of non-heme iron and manganese catalysts that mimic the reactivity of Rieske dioxygenases. − In this regard, Que and co-workers reported the first example of asymmetric cis -dihydroxylation by non-heme iron complexes in the presence of large excess of olefins (e.g., cat/H 2 O 2 /substrate = 1:20:1000), and the enantiomeric excess (ee) of cis -diols was improved from 82 to 97% upon replacement of the trans -1,2-diaminocyclohexane backbone with a more rigid bipyrrolidine; this pioneering work provides a starting point for the development of synthetic cis -dihydroxylation catalysts as functional mimics of Rieske dioxygenases, although the use of large excess of olefins relative to the oxidant is required to obtain satisfied turnover numbers and high product ratios of cis -dihydroxylation to epoxidation . Only recently have non-heme iron complexes supported by tetradentate aminoquinoline ligands been demonstrated to engender highly enantioselective cis -dihydroxylation under substrate-limiting conditions by Che, Wang, and their co-workers (Figure B) …”

“…While significant advances have been made in developing biologically inspired non-heme iron catalysts for enantioselective cis -dihydroxylation of olefins, , there are only two manganese complexes reported so far for the asymmetric cis -dihydroxylation of olefins. , One example is by Feringa and co-workers, reporting that a μ-oxo chiral carboxylate-bridged dinuclear manganese­(III) complex was capable of performing cis -dihydroxylation with H 2 O 2 as an oxidant (Figure C); however, they only examined the asymmetric cis -dihydroxylation of 2,2-dimethylchromene affording 50% conversion and 54% ee . In another example, a non-heme manganese-catalyzed enantioselective alkene cis -dihydroxylation system with a potentially practical importance was reported by Che and co-workers with utilizing a non-heme manganese complex bearing a tetradentate aminoquinoline ligand as a catalyst (Figure C), in which electron-deficient alkenes were converted to cis -diols with preparable yields and up to 96% ee together with significant amounts of epoxidation products (8.0–30%) …”

Seeing the cis-Dihydroxylating Intermediate: A Mononuclear Nonheme Iron-Peroxo Complex in cis-Dihydroxylation Reactions Modeling Rieske Dioxygenases

“…Inspired by the iron-dependent arene cis -dihydroxylating Rieske dioxygenases, synthetic nonheme iron complexes have been extensively explored as catalysts for the cis -dihydroxylation of olefins using hydrogen peroxide (H 2 O 2 ) as a terminal oxidant, to replace the toxic and expensive osmium (and related high-valent compounds with cis -dioxo groups) catalyzed cis -dihydroxylation of olefins . As a result, several landmark discoveries, pioneered by Que, Che, and Costas, were observed in the nonheme iron-catalyzed (asymmetric) cis -dihydroxylation of olefins by H 2 O 2 . − Regarding the cis -dihydroxylating intermediate, an iron(V)-oxo-hydroxo (HO-Fe V O) species, which is the product of the O–O bond heterolysis of an iron(III)-hydroperoxo intermediate, has been proposed as the active cis -dihydroxylating intermediate responsible for the cis -dihydroxylation of olefins in biomimetic systems (Figure S1b); ,,, in several cases, other iron–oxygen intermediates, such as iron(III)-superoxo and iron(III)-hydroperoxo, have been proposed as a potent oxidant in the cis -dihydroxylation reactions. ,, Accordingly, reaction mechanisms were proposed with an assumption that an HO-Fe V O species is the cis -dihydroxylating intermediate that reacts with olefins to yield cis -diols (Figure S1b). However, it should be noted that such an HO-Fe V O species has never been detected in any catalytic cis -dihydroxylation reactions and that the cis -dihydroxylation of olefins has never been attempted with isolated HO-Fe V O species.…”