Abstract:Readily prepared allylic zinc halides undergo SN 2-type substitutions with allylic bromides in a 1:1 mixture of THF and DMPU providing 1,5-dienes regioselectively. The allylic zinc species reacts at the most branched end (γ-position) of the allylic system furnishing exclusively γ,α'-allyl-allyl cross-coupling products. Remarkably, the double bond stereochemistry of the allylic halide is maintained during the cross-coupling process. Also several functional groups (ester, nitrile) are tolerated. This cross-coupl… Show more
“…[35] In order to rationalize the exquisite regioselectivity observed in transformations with unsymmetrically substituted allylic zinc species,t heoretical calculations have been performed for the reaction of propellane (1)w ith prenylzinc bromide complexed with lithium chloride (7d), whose sole reaction product is the BCP 9k (Scheme 6). Following effectively the same protocol used in earlier studies of organozinc reagents, [36] free energies in THF solution have been calculated at the SMD(THF)/B2PLYP/def2-TZVPP level of theory (see SI for further details). Calculations start from the cubic cluster 25 assembled from 2equivalents of LiCl, ZnBr 2 , [37] and prenylzinc bromide (7k).…”
We report ar ange of highly regioselective openings of [1.1.1]propellane with various allylic zinc halides,aswell as zinc enolates of ketones,e sters and nitriles.T he resulting zincated bicyclopentanes (BCPs) were trapped with arange of electrophiles including acyl chlorides,sulfonothioates,hydroxylamino benzoates,t osyl cyanide as well as aryl and allyl halides,generating highly functionalized BCP-derivatives.The unusually high regioselectivity of these reactions has been rationalized using DFT calculations.Abioisostere of the synthetic opioid pethidine was prepared in 95 %y ield in one step using this method.
“…[35] In order to rationalize the exquisite regioselectivity observed in transformations with unsymmetrically substituted allylic zinc species,t heoretical calculations have been performed for the reaction of propellane (1)w ith prenylzinc bromide complexed with lithium chloride (7d), whose sole reaction product is the BCP 9k (Scheme 6). Following effectively the same protocol used in earlier studies of organozinc reagents, [36] free energies in THF solution have been calculated at the SMD(THF)/B2PLYP/def2-TZVPP level of theory (see SI for further details). Calculations start from the cubic cluster 25 assembled from 2equivalents of LiCl, ZnBr 2 , [37] and prenylzinc bromide (7k).…”
We report ar ange of highly regioselective openings of [1.1.1]propellane with various allylic zinc halides,aswell as zinc enolates of ketones,e sters and nitriles.T he resulting zincated bicyclopentanes (BCPs) were trapped with arange of electrophiles including acyl chlorides,sulfonothioates,hydroxylamino benzoates,t osyl cyanide as well as aryl and allyl halides,generating highly functionalized BCP-derivatives.The unusually high regioselectivity of these reactions has been rationalized using DFT calculations.Abioisostere of the synthetic opioid pethidine was prepared in 95 %y ield in one step using this method.
“…Meanwhile, the iodine moving to the aryl side in the reductive products 3 implied that an excellent regioselectivity with cMAVIs could be achieved, which is challenging in unsymmetrical cDAIs. Thus, we hypothesized that our synthesized cMAVIs might provide a synthon platform and achieve the complete regioselectivity under transition-metal-free condition, which is highly demanded in the field of synthetic chemistry ( Ellwart et al., 2016 ). Figure 2 Exploration of New cMAVIs and Their Reactivity (A) The structure of novel cMAVIs with different substitutes on β-position.…”
Summary
Cross-coupling reactions between aryl iodide and nucleophiles have been well developed. Iodoniums equipped with a reactive C-I(III) bond accelerate cross-coupling reactions of aryl iodide. Among them, cyclic diaryliodoniums are more atom economical; however; they are often in the trap of metal reliance and encounter regioselectivity issues. Now, we have developed a series of highly reactive cyclic monoaryl-vinyl iodoniums that can be tuned to construct C-N, C-O, and C-C bonds without metal catalysis. Under promotion of triethylamine, coupling reactions with aniline, phenol, aromatic acid, and indole proceed rapidly and regioselectively at room temperature. The carbene species is conceptualized as a key intermediate in our mechanism model. Furthermore, the coupling products enable diversity-oriented synthesis strategy to further build up a chemical library of diverse heterocyclic fragments that are in demand in the drug discovery field. Our current work provides a deep insight into the synthetic application of these highly reactive cyclic iodoniums.
“…Das einzige beobachtete Produkt dieser Reaktion ist das BCP 9k (Schema 6). Unter Befolgung desselben Protokolls,w elches in früheren Studien von Organozinkreagenzien eingesetzt wurde, [36] wurden die freien Enthalpien in THF-Lçsung auf SMD(THF)/B2PLYP/def2-TZVPP-Niveau Schema 11. Synthese und Kristallstruktur von BCP-Pethidin 6.…”
Wirb erichten über eine Reihe von hochregioselektiven Öffnungen von [1.1.1]Propellan mit verschiedenen allylischen Zinkhalogeniden, sowie mit Zinkenolaten von Ketonen, Estern und Nitrilen. Die resultierenden zinkierten Bicyclopentane (BCPs) wurden mit einer Reihe von Elektrophilen abgefangen, einschließlich Carbonsäurechloriden, Sulfonothioaten, Hydroxylaminobenzoaten, Tosylcyanid sowie Arylund Allylhalogeniden. Dadurchwurden hochfunktionalisierte BCP-Derivate erzeugt. Die ungewçhnlichh ohe Regioselektivitätd ieser Reaktionen wurde mittels DFT-Berechnungen rationalisiert. Ein Bioisoster des synthetischen Opioids Pethidin wurdem it Hilfe dieser Methodik in einem Schritt in 95 % Ausbeute hergestellt. Schema 1. A) Reaktion von [1.1.1]Propellan (1)mit Radikalen und Anionen. B) BCP-Analoga ausgewählter pharmazeutischer Verbindungen. Schema 2. Reaktionen von [1.1.1]Propellan (1)m it organometallischen Reagenzien.
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