Heterodiene Additions

Boger, Dale L.

doi:10.1016/b978-0-08-052349-1.00130-x

Cited by 99 publications

(21 citation statements)

References 299 publications

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“…However, bimolecular bond forming reactions present a greater challenge, since both substrates must be bound in the proper relative orientation in order to accelerate the reaction and induce stereoselectivity. Also, previous successes with computational enzyme design have involved general acid-base catalysis and covalent catalysis, but the Diels-Alder reaction instead can be primarily influenced by modulation of molecular orbital energies (6). To investigate the feasibility of designing intermolecular Diels-Alder enzyme catalysts we chose to focus on the well-studied model Diels-Alder reaction between 4-carboxybenzyl trans -1,3-butadiene-1-carbamate and N,N- dimethylacrylamide (Fig.…”

mentioning

confidence: 99%

“…For normal-electron-demand Diels–Alder reactions, Frontier Molecular Orbital Theory dictates that the interaction of the highest occupied molecular orbital (HOMO) of the diene with the lowest unoccupied molecular orbital (LUMO) of the dienophile is the dominant interaction in the transition state (6). The reaction can be catalyzed by bringing the energies of the HOMO and LUMO closer together.…”

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confidence: 99%

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Computational Design of an Enzyme Catalyst for a Stereoselective Bimolecular Diels-Alder Reaction

Siegel

Zanghellini

Lovick

et al. 2010

Science

828

722

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The Diels-Alder reaction is a cornerstone in organic synthesis, forming two carbon-carbon bonds and up to four new stereogenic centers in one step. No naturally occurring enzymes have been shown to catalyze bimolecular Diels-Alder reactions. We describe the de novo computational design and experimental characterization of enzymes catalyzing a bimolecular Diels-Alder reaction with high stereoselectivity and substrate specificity. X-ray crystallography confirms that the structure matches the design for the most active of the enzymes, and binding site substitutions reprogram the substrate specificity. Designed stereoselective catalysts for carbon-carbon bond forming reactions should be broadly useful in synthetic chemistry.

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confidence: 99%

mentioning

confidence: 99%

Computational Design of an Enzyme Catalyst for a Stereoselective Bimolecular Diels-Alder Reaction

Siegel

Zanghellini

Lovick

et al. 2010

Science

828

722

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“…The first is a two‐step pathway, including the formation of zwitterionic intermediate I from the 1,4‐conjugated addition of 1b to 8a (path a) . The second one may occur through a concerted hetero‐Diels‐Alder cycloaddition (path b) …”

Section: Resultsmentioning

confidence: 99%

“…62,63 The second one may occur through a concerted hetero-Diels-Alder cycloaddition (path b). [64][65][66] Figure 2 depicts rotamers 1b-A and 1b-B of the chiral auxiliary 1b. The former corresponds to the conformation observed in the X-ray structure of 29b, in which the benzylic proton is quasi coplanar in relation to the plane of the heterocycle, leaving the methyl and phenyl groups at the beta and alpha positions, respectively.…”

Section: Reaction Mechanisms and Diastereoselectivity Of The Procesmentioning

confidence: 99%

Enantiopure 4‐oxazolin‐2‐ones and 4‐methylene‐2‐oxazolidinones as chiral building blocks in a divergent asymmetric synthesis of heterocycles

et al. 2019

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Enantiopure 3‐((R)‐ and 3‐((S)‐1‐phenylethyl)‐4‐oxazoline‐2‐ones were evaluated as chiral building blocks for the divergent construction of heterocycles with stereogenic quaternary centers. The N‐(R)‐ or N‐(S)‐1‐phenylethyl group of these compounds proved to be an efficient chiral auxiliary for the asymmetric induction of the 4‐ and 5‐positions of the 4‐oxazolin‐2‐one ring through thermal and MW‐promoted nucleophilic conjugated addition to Michael acceptors and alkyl halides. The resulting adducts were transformed via a cascade process into fused six‐membered carbo‐ and heterocycles. The structure of the reaction products depended on the electrophiles and reaction conditions used. Alternative isomeric 4‐methylene‐2‐oxazolidinones served as chiral precursors for a versatile and divergent approach to highly substituted cyclic carbamates. DFT quantum calculations showed that the formation of bicyclic pyranyl compounds was generated by a diastereoselective concerted hetero‐Diels‐Alder cycloaddition.

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“…As mentioned before, the construction of FR-900482 was thought to occur by intramolecular hetero Diels–Alder reaction of a compound of type 32 ( Scheme 8 ) [ 51 ]. After careful analysis, it was envisioned that the reaction could occur either in the bridged mode to give the FR series (compounds 3 and 4 ) or in the fused mode to give access to mitomycins.…”

Section: Discussionmentioning

confidence: 99%

Mitomycins syntheses: a recent update

Andrez¹

2009

Beilstein J. Org. Chem.

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SummaryMitomycins are a class of very potent antibacterial and anti-cancer compounds having a broad activity against a range of tumours. They have been used in clinics since the 1960’s, and the challenges represented by their total synthesis have challenged generations of chemists. Despite these chemical and medicinal features, these compounds, in racemic form, have succumbed to total synthesis only four times over the last 30 years.

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Heterodiene Additions

Cited by 99 publications

References 299 publications

Computational Design of an Enzyme Catalyst for a Stereoselective Bimolecular Diels-Alder Reaction

Computational Design of an Enzyme Catalyst for a Stereoselective Bimolecular Diels-Alder Reaction

Enantiopure 4‐oxazolin‐2‐ones and 4‐methylene‐2‐oxazolidinones as chiral building blocks in a divergent asymmetric synthesis of heterocycles

Mitomycins syntheses: a recent update

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