Iron‐Catalyzed Asymmetric Olefin cis‐Dihydroxylation with 97 % Enantiomeric Excess

Abstract

The rising number of pharmaceuticals with chiral centers [1] has heightened the necessity to discover catalysts that provide asymmetric induction into the products of their respective reactions.[2] In addition, stringent constraints on trace impurities allowed in the marketed pharmaceutical products make the use of catalysts composed of physiologically benign metal centers increasingly attractive. The cis-dihydroxylation of olefins has become an important chemical reaction in the design of pharmaceuticals [3] and natural product synthesis [4] because this reaction is both stereospecific and, through the use of the Sharpless asymmetric dihydroxylation (AD) mixes, enantiospecific.[5] A potential disadvantage of the Sharpless procedure is the extraordinary toxicity associated with the osmium metal in the AD mixes.In contrast, nature has evolved an important class of nonheme iron enzymes, called the Rieske dioxygenases, that perform a novel, asymmetric cis-dihydroxylation of arene C = C bonds.[6] Such enzymes can be used as biocatalysts, [7] but they are effective for only a narrow range of substrates, limiting their applicability. The catalytically relevant mononuclear iron center in the Rieske dioxygenases is coordinated by the 2-His-1-carboxylate facial triad, [8] a common structural motif among nonheme iron enzymes, [9] which leaves cis-oriented available coordination sites on the iron octahedron for the activation of dioxygen. Inspired by these enzymes, researchers have developed the first examples of biomimetic complexes involving iron [10] or manganese [11] that catalyze olefin cisdihydroxylation using H 2 O 2 as oxidant. Two of these complexes (4 and 5 in Figure 1) incorporate the optically active trans-1,2-diaminocyclohexane backbone into the ligand framework and exhibit asymmetric cis-dihydroxylation of cis-2-heptene with ee values of 29 and 79 %.[10c] With the goal of achieving greater ee values, the trans-1,2-diaminocyclohexane unit was replaced by bipyrrolidine to give the tetradentate ligands (R,R)-BPBP, (R,R)-BQBP, and (R,R)-6-Me 2 -BPBP (Figure 1). Herein, we compare the asymmetric cis-dihydroxylation abilities of three iron complexes and find the 6-Me 2 -BPBP complex capable of achieving up to 97 % enantiomeric excess of the cis-diol product from two cis-disubstituted olefins. These ee values are comparable to those obtained with the osmium-based AD mixes.The ligands (R,R)-BPBP, (R,R)-BQBP, and (R,R)-6-Me 2 -BPBP ( Figure 1) were obtained by following literature procedures, [12] and corresponding iron(II) complexes were obtained by the reactions of equimolar amounts of ligand and Fe II (OTf) 2 ·2 NCMe [13] in CH 2 Cl 2 under a N 2 atmosphere (OTf = trifluoromethanesulfonate). Overnight stirring and subsequent solvent removal gave light brown powders, which were recrystallized from CH 2 Cl 2 /ether to afford pale yellow crystals, formulated as [Fe . These crystals were suitable for X-ray crystallographic analysis, [14] and the structures of the three complexes are shown in Figure 2. [15] In all thre...

Fe(PyTACN)‐Catalyzed cis‐Dihydroxylation of Olefins with Hydrogen Peroxide

“…[44] Further optimization of this family of catalysts was devised by introducing modifications in the positions 4 and 6 of the pyridine ligand. [37,[39][40][41][42][43][44][45][46][47][48][49][50][52][53][54][55][56] The results on the catalytic activity of the series of complexes where substitution is introduced at position 4 of the pyridine (1)(2)(3)(4)(5) shows that the chemoselectivity towards epoxidation vs. cis-dihydroxylation is governed only to a minor extent by electronic effects imposed by the pyridine ring. On the other hand, modifications in position 6 were presumed to mainly introduce steric effects, because this position is in close spatial proximity to the cis-available coordination sites, initially occupied by labile triflate ligands, and where oxidation of the substrate takes place.…”

“…Because of that, more convenient alternatives are actively pursued. [41][42][43][44] Iron catalysts which contain ligands that combine N and O donor sites, and that are more closely related to the actual His 2 Carboxylate-facial triad donor set present in the enzyme, [32,45] have been also explored (Scheme 1). [20][21][22][23][24][25][26] Towards this end, organic peroxides have been recently explored with promising results.…”

Biomimetic Iron‐Catalyzed Asymmetric Epoxidations: Fundamental Concepts, Challenges and Opportunities

“…[190] The mechanism of this reaction has been one of the most remarkable. [190] The mechanism of this reaction has been one of the most remarkable.…”

“…[190] The mechanism of this reaction has been one of the most remarkable. [141] Accordingly, formation of epoxides by Q proceeds through two separate single electron [190] transfer steps involving radical intermediate A and requiring a higher activation barrier than H peroxo in which the reaction is a two electron process. It was proposed that depending on which oxygen atom of the the oxo-hydroxo species attacks the alkene double bond first, either selective epoxidation or dihydroxylation can take place.…”

Organocatalytic Asymmetric Hydrolysis of Epoxides

“…[18] While enantioselective syn-dihydroxylations of olefins are well developed, analogous non-enzymatic asymmetric antidihydroxylations are unknown. [9,19] We reasoned that our approach could potentially be utilized in this context. In fact, the Prilezhaev reaction, that is, the oxidation of alkenes with simple peracids, delivers both an epoxide and a carboxylic acid, which is the exact combination of substrates for the reaction reported here.…”