The development of endo-selective epoxide-opening cascades in water

Morten, Christopher J.; Byers, Jeffery A.; Dyke, Aaron R. Van; Vilotijević, Ivan; Jamison, Timothy F.

doi:10.1039/b816697h

Cited by 98 publications

(38 citation statements)

References 68 publications

(121 reference statements)

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“…It is clear from the data in Table 1 that selectivity in the cyclization reactions under neutral aqueous conditions is very sensitive to the identity of the template and the size of the ring being formed (10)(11)(12). We were particularly surprised to find that a 1:1 mixture of products resulted from the seemingly minor change from 1a to 1b, which differ only by the replacement of an oxygen atom with a CH 2 group in the template (entries 1 and 2).…”

Section: Resultsmentioning

confidence: 99%

“…In addition to uncovering the specific details about epoxy alcohol cyclization reactions, these mechanistic studies are relevant to the biosynthetic proposal (18) for the formation of the ladder polyether natural products. The very slow reaction rates observed for 1a and even slower rates for cascade reactions of multiple epoxides, such as 4 and 6 (12,24), are problematic for a biosynthetic proposal involving consecutive or concurrent epoxy alcohol cyclizations promoted by neutral water. The data presented above suggest rate constants for endo cyclizations to be on the order of 10 −5 ·s −1 at 300 K, which translates to a half-life of 16.6 h. These rates seem unlikely under physiological conditions where metabolism or extrusion of intermediates during a cascade reaction would compete.…”

Section: Implications For the Biogenisis Of The Ladder Polyether Naturalmentioning

confidence: 99%

“…1) (10)(11)(12). Exceptional reactivity and selectivity were observed only when two criteria were satisfied: The substrate contained a sixmembered tetrahydropyran ring, and the solvent used was water at pH 7.0.…”

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Entropic factors provide unusual reactivity and selectivity in epoxide-opening reactions promoted by water

Byers

Jamison

2013

Proc. Natl. Acad. Sci. U.S.A.

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Despite the myriad of selective enzymatic reactions that occur in water, chemists have rarely capitalized on the unique properties of this medium to govern selectivity in reactions. Here we report detailed mechanistic investigations of a water-promoted reaction that displays high selectivity for what is generally a disfavored product. A combination of structural and kinetic data indicates not only that synergy between substrate and water suppresses undesired pathways but also that water promotes the desired pathway by stabilizing charge in the transition state, facilitating proton transfer, doubly activating the substrate for reaction, and perhaps most remarkably, reorganizing the substrate into a reactive conformation that leads to the observed product. This approach serves as an outline for a general strategy of exploiting solvent-solute interactions to achieve unusual reactivity in chemical reactions. These findings may also have implications in the biosynthesis of the ladder polyether natural products, such as the brevetoxins and ciguatoxins.entropic control | biomimetic G iven its simple structure and low molecular weight, water is a remarkably complex substance. Several landmark investigations (1) have revealed the ability of water to self-assemble to form sophisticated dynamic hydrogen bond networks, which accounts for its unusual properties, such as its high boiling point and high surface tension (2). Despite the unique properties that it offers and that nature has exploited, water is generally eschewed in synthetic chemistry largely because of chemical incompatibility with many commonly used reagents and the low aqueous solubility of many organic molecules coupled with the attendant assumption that homogeneity is required for reactivity. Although several important examples of remarkable reactivity have been documented for reactions carried out in water (3-5), on the surface of water (6, 7), or in micelles suspended in water (8, 9), utilization of the "biological solvent" in organic reactions remains uncommon.We became acutely aware of the remarkable properties of water when we discovered that neutral aqueous solutions of epoxy alcohol 1a underwent a spontaneous and selective "endo" cyclization reaction to form 6,6-fused bicyclic product 2a (Fig. 1) (10-12). Exceptional reactivity and selectivity were observed only when two criteria were satisfied: The substrate contained a sixmembered tetrahydropyran ring, and the solvent used was water at pH 7.0. These surprising results were counter to a set of general empirical rules put forth by Baldwin for cyclization reactions, which state that the smaller ring product resulting from what is commonly called an exo cyclization is favored for similar reactions (13). The tetrahydropyranol ring, therefore, appeared to "template" the endo cyclization pathway to form the larger ring product with water playing a critical yet heretofore unknown role.Moreover, 2a is a substructure found in a large family of natural products commonly referred to as the ladder polyethers (e....

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Section: Resultsmentioning

confidence: 99%

Section: Implications For the Biogenisis Of The Ladder Polyether Naturalmentioning

confidence: 99%

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Entropic factors provide unusual reactivity and selectivity in epoxide-opening reactions promoted by water

Byers

Jamison

2013

Proc. Natl. Acad. Sci. U.S.A.

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“…[118][119][120] The ring opening of epoxides is an important and well-known reaction that is known to be catalyzed by Lewis acidic metal ions. [118][119][120] In such a reaction, activation of the epoxide ring is a prerequisite, and this can be achieved by using an appropriate Lewis acid followed by ring opening by using an appropriate nucleophile.…”

Section: Ring-opening Reactionsmentioning

confidence: 99%

Manganese Complexes of Pyrrole‐ and Indolecarboxamide Ligands: Synthesis, Structure, Electrochemistry, and Applications in Oxidative and Lewis‐Acid‐Assisted Catalysis

2015

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This work shows the synthesis and structural, spectroscopic, and electrochemical properties of MnIII complexes supported with pyrrole‐ and indolecarboxamide ligands. In all cases, the respective ligand constitutes a N4 coordination sphere about the MnIII ion. The MnIII complexes of pyrrolecarboxamide ligands are square pyramidal with a fifth Cl atom, whereas analogous complexes of indolecarboxamide ligands are essentially square planar. Electrochemical studies reveal highly negative MnIII/II and moderately positive MnIV/III redox potentials. In situ generated Mn4+ species of the pyrrolecarboxamide ligands were characterized by absorption and electron paramagnetic resonance spectroscopy. All complexes functioned as catalysts in olefin epoxidation reactions by using PhIO as the oxo‐transfer agent. All complexes also acted as Lewis acid catalysts for ring‐opening reactions of assorted epoxides with various nucleophiles. We also show a one‐pot, two‐step epoxidation reaction followed by ring opening, which illustrates the catalytic significance of the present complexes. Importantly, MnIII complexes carrying electron‐donating substituents on the ligand were found to be better catalysts.

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“…While diepoxides 279 and 280 also produced some of the desired products upon acidic activation, only aqueous conditions afforded any of the THP triad 284 from diepoxide 281. Aqueous epoxide-opening cascades overcome the need for methyl substituents to be uniformly distributed on each epoxide and can accommodate both types of trisubstituted epoxides in combination with disubstituted epoxides [203].…”

Section: Epoxide-opening Cascades In the Synthesis Of Polycyclicmentioning

confidence: 99%

Biomimetic Synthesis of Polyether Natural Products via Polyepoxide Opening

Vilotijević

Jamison

2011

Biomimetic Organic Synthesis

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The development of endo-selective epoxide-opening cascades in water

Cited by 98 publications

References 68 publications

Entropic factors provide unusual reactivity and selectivity in epoxide-opening reactions promoted by water

Entropic factors provide unusual reactivity and selectivity in epoxide-opening reactions promoted by water

Manganese Complexes of Pyrrole‐ and Indolecarboxamide Ligands: Synthesis, Structure, Electrochemistry, and Applications in Oxidative and Lewis‐Acid‐Assisted Catalysis

Biomimetic Synthesis of Polyether Natural Products via Polyepoxide Opening

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The development of endo-selective epoxide-opening cascades in water

Cited by 98 publications

References 68 publications

Entropic factors provide unusual reactivity and selectivity in epoxide-opening reactions promoted by water

Entropic factors provide unusual reactivity and selectivity in epoxide-opening reactions promoted by water

Manganese Complexes of Pyrrole‐ and ­Indolecarboxamide Ligands: Synthesis, Structure, Electrochemistry, and Applications in Oxidative and Lewis‐Acid‐­Assisted Catalysis

Biomimetic Synthesis of Polyether Natural Products via Polyepoxide Opening

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Manganese Complexes of Pyrrole‐ and Indolecarboxamide Ligands: Synthesis, Structure, Electrochemistry, and Applications in Oxidative and Lewis‐Acid‐Assisted Catalysis