The Experts below are selected from a list of 309 Experts worldwide ranked by ideXlab platform
James A Bull - One of the best experts on this subject based on the ideXlab platform.
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lithium catalyzed thiol alkylation with tertiary and secondary alcohols synthesis of 3 sulfanyl Oxetanes as bioisosteres
Chemistry: A European Journal, 2018Co-Authors: Rosemary A Croft, James J Mousseau, Chulho Choi, James A BullAbstract:: 3-Sulfanyl-Oxetanes are presented as promising novel bioisosteric replacements for thioesters or benzyl sulfides. From oxetan-3-ols, a mild and inexpensive Li catalyst enables chemoselective C-OH activation and thiol alkylation. Oxetane sulfides are formed from various thiols providing novel motifs in new chemical space and specifically as bioisosteres for thioesters due to their similar shape and electronic properties. Under the same conditions, various π-activated secondary and tertiary alcohols are also successful. Derivatization of the oxetane sulfide linker provides further novel oxetane classes and building blocks. Comparisons of key physicochemical properties of the oxetane compounds to selected carbonyl and methylene analogues indicate that these motifs are suitable for incorporation into drug discovery efforts.
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Oxetanes recent advances in synthesis reactivity and medicinal chemistry
Chemical Reviews, 2016Co-Authors: James A Bull, Owen A Davis, Rosemary A Croft, Robert Doran, Kate F MorganAbstract:The four-membered oxetane ring has been increasingly exploited for its contrasting behaviors: its influence on physicochemical properties as a stable motif in medicinal chemistry and its propensity to undergo ring-opening reactions as a synthetic intermediate. These applications have driven numerous studies into the synthesis of new oxetane derivatives. This review takes an overview of the literature for the synthesis of oxetane derivatives, concentrating on advances in the last five years up to the end of 2015. These methods are clustered by strategies for preparation of the ring and further derivatization of preformed oxetane-containing building blocks. Examples of the use of Oxetanes in medicinal chemistry are reported, including a collation of oxetane derivatives appearing in recent patents for medicinal chemistry applications. Finally, examples of oxetane derivatives in ring-opening and ring-expansion reactions are described.
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2 sulfinyl Oxetanes synthesis stability and reactivity
Synlett, 2015Co-Authors: Kate F Morgan, Ian A Hollingsworth, Rosemary A Croft, Robert Doran, James A BullAbstract:The synthesis of 2-sulfinyl Oxetanes is described by a C–C bond-forming cyclisation strategy. Oxetanes bearing electron-poor aryl sulfoxides are shown to be viable targets using this strategy. We report investigations into the sulfoxide magnesium exchange on 2-sulfinyl Oxetanes, which resulted in products formed via ligand exchange and ligand coupling pathways. The sulfinyl Oxetanes can be readily oxidised to the sulfonyl Oxetanes.
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recent advances in the synthesis of 2 substituted Oxetanes
Synlett, 2015Co-Authors: Owen A Davis, James A BullAbstract:Recent interest in Oxetanes in medicinal chemistry and as synthetic intermediates has led to the development of a number of methods for the synthesis of more functionalized and highly substituted oxetane derivatives. Here we review cyclization approaches for the preparation of 2-substituted Oxetanes. Methods involving C–O bond formation, as well as recently developed C–C bond forming cyclization strategies are highlighted.
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synthesis of di tri and tetrasubstituted Oxetanes by rhodium catalyzed oh insertion and cc bond forming cyclization
Angewandte Chemie, 2014Co-Authors: Owen A Davis, James A BullAbstract:Oxetanes offer exciting potential as structural motifs and intermediates in drug discovery and materials science. Here an efficient strategy for the synthesis of oxetane rings incorporating pendant functional groups is described. A wide variety of oxetane 2,2-dicarboxylates were accessed in high yields, including functionalized 3-/4-aryl- and alkyl-substituted Oxetanes and fused oxetane bicycles. Enantioenriched alcohols provided enantioenriched Oxetanes with complete retention of configuration. The oxetane products were further derivatized, while the ring was maintained intact, thus highlighting their potential as building blocks for medicinal chemistry.
Kate F Morgan - One of the best experts on this subject based on the ideXlab platform.
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Oxetanes recent advances in synthesis reactivity and medicinal chemistry
Chemical Reviews, 2016Co-Authors: James A Bull, Owen A Davis, Rosemary A Croft, Robert Doran, Kate F MorganAbstract:The four-membered oxetane ring has been increasingly exploited for its contrasting behaviors: its influence on physicochemical properties as a stable motif in medicinal chemistry and its propensity to undergo ring-opening reactions as a synthetic intermediate. These applications have driven numerous studies into the synthesis of new oxetane derivatives. This review takes an overview of the literature for the synthesis of oxetane derivatives, concentrating on advances in the last five years up to the end of 2015. These methods are clustered by strategies for preparation of the ring and further derivatization of preformed oxetane-containing building blocks. Examples of the use of Oxetanes in medicinal chemistry are reported, including a collation of oxetane derivatives appearing in recent patents for medicinal chemistry applications. Finally, examples of oxetane derivatives in ring-opening and ring-expansion reactions are described.
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2 sulfinyl Oxetanes synthesis stability and reactivity
Synlett, 2015Co-Authors: Kate F Morgan, Ian A Hollingsworth, Rosemary A Croft, Robert Doran, James A BullAbstract:The synthesis of 2-sulfinyl Oxetanes is described by a C–C bond-forming cyclisation strategy. Oxetanes bearing electron-poor aryl sulfoxides are shown to be viable targets using this strategy. We report investigations into the sulfoxide magnesium exchange on 2-sulfinyl Oxetanes, which resulted in products formed via ligand exchange and ligand coupling pathways. The sulfinyl Oxetanes can be readily oxidised to the sulfonyl Oxetanes.
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2 aryl sulfonyl Oxetanes as designer 3 dimensional fragments for fragment screening synthesis and strategies for functionalisation
Chemical Communications, 2014Co-Authors: Kate F Morgan, Ian A Hollingsworth, James A BullAbstract:2-Sulfonyl-Oxetanes have been prepared, affording non-planar structures with desirable physicochemical properties for fragment based drug discovery. The oxetane motif was formed by an intramolecular C–C bond formation. The fragments were further functionalised via organometallic intermediates at the intact oxetane and aromatic rings.
Amy R Howell - One of the best experts on this subject based on the ideXlab platform.
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recent applications of Oxetanes in the synthesis of heterocyclic compounds
Journal of Organic Chemistry, 2015Co-Authors: Christian A Malapit, Amy R HowellAbstract:Oxetanes are valuable intermediates in organic synthesis, and strategic manipulations of this strained heterocycle continue to emerge. In this Synopsis, recent, distinct approaches to construct heterocyclic systems using Oxetanes are described. These include ring expansion, ring opening, and C-2 functionalization.
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2 alkylidene Oxetanes by stereospecific elimination of mesylates
Tetrahedron Letters, 2007Co-Authors: Paul S Sabila, Amy R HowellAbstract:α-MesyloxyOxetanes undergo stereospecific elimination to 2-alkylidene Oxetanes upon treatment with potassium t-butoxide.
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directed ring opening of 1 5 dioxaspiro 3 2 hexanes selective formation of 2 2 disubstituted Oxetanes
Journal of Organic Chemistry, 2003Co-Authors: Rosa Taboada, Grace G Ordonio, Albert Ndakala, Amy R Howell, Paul R RablenAbstract:1,5-Dioxaspiro[3.2]hexanes undergo ring-opening reactions with many heteroatom nucleophiles to provide α-substituted-β‘-hydroxy ketones. However, certain Lewis acidic nucleophiles provide 2,2-disubstituted Oxetanes. Herein, the results of reactions of 3-phenyl-1,5-dioxaspiro[3.2]hexane with a variety of nitrogen-containing heteroaromatic bases are reported. There appears to be a correlation between the pKa of the nucleophile and the reaction outcome with more acidic nucleophiles providing 2,2-disubstituted Oxetanes. Moreover, the mode of ring opening can be directed toward the substituted oxetane by the addition of a Lewis acid. These results are rationalized by calculation of stationary points on the potential energy surfaces for the various possible reaction pathways using ab initio molecular orbital methods.
Paul R Rablen - One of the best experts on this subject based on the ideXlab platform.
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directed ring opening of 1 5 dioxaspiro 3 2 hexanes selective formation of 2 2 disubstituted Oxetanes
Journal of Organic Chemistry, 2003Co-Authors: Rosa Taboada, Grace G Ordonio, Albert Ndakala, Amy R Howell, Paul R RablenAbstract:1,5-Dioxaspiro[3.2]hexanes undergo ring-opening reactions with many heteroatom nucleophiles to provide α-substituted-β‘-hydroxy ketones. However, certain Lewis acidic nucleophiles provide 2,2-disubstituted Oxetanes. Herein, the results of reactions of 3-phenyl-1,5-dioxaspiro[3.2]hexane with a variety of nitrogen-containing heteroaromatic bases are reported. There appears to be a correlation between the pKa of the nucleophile and the reaction outcome with more acidic nucleophiles providing 2,2-disubstituted Oxetanes. Moreover, the mode of ring opening can be directed toward the substituted oxetane by the addition of a Lewis acid. These results are rationalized by calculation of stationary points on the potential energy surfaces for the various possible reaction pathways using ab initio molecular orbital methods.
Thierry Lequeux - One of the best experts on this subject based on the ideXlab platform.
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synthesis of fluorine containing 3 3 disubstituted Oxetanes and alkylidene Oxetanes
ChemInform, 2015Co-Authors: Romain Laporte, Anais Prunier, Emmanuel Pfund, Luigi A Agrofoglio, Thierry LequeuxAbstract:The introduction of fluoroalkylidenes onto 3-oxetanone, 3-azetidinone, and cyclobutanone rings is achieved through base mediated reaction with various sulfones.
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synthesis of fluorine containing 3 3 disubstituted Oxetanes and alkylidene Oxetanes
European Journal of Organic Chemistry, 2015Co-Authors: Romain Laporte, Anais Prunier, Emmanuel Pfund, Luigi A Agrofoglio, Thierry LequeuxAbstract:Access to fluoroalkylidene-Oxetanes and -azetidines was realized from 3-oxetanone, 3-azetidinone, and fluorosulfones through the Julia–Kocienski reaction. This approach allows the preparation of new precursors of fluorinated four-membered rings that contain a nucleic base, an ester or aryl sulfone function, and a pyrrolidine ring. Benzothiazolyl-sulfone-mediated aza-Michael addition reaction of nitrogen nucleophiles enables access to 3,3-disubstituted Oxetanes.
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Synthesis of Fluorine‐Containing 3,3‐Disubstituted Oxetanes and Alkylidene Oxetanes
European Journal of Organic Chemistry, 2015Co-Authors: Romain Laporte, Anais Prunier, Emmanuel Pfund, Luigi A Agrofoglio, Thierry LequeuxAbstract:Access to fluoroalkylidene-Oxetanes and -azetidines was realized from 3-oxetanone, 3-azetidinone, and fluorosulfones through the Julia–Kocienski reaction. This approach allows the preparation of new precursors of fluorinated four-membered rings that contain a nucleic base, an ester or aryl sulfone function, and a pyrrolidine ring. Benzothiazolyl-sulfone-mediated aza-Michael addition reaction of nitrogen nucleophiles enables access to 3,3-disubstituted Oxetanes.
