scholarly journals Optimisation and Scope of a Palladium-Catalysed Allylic Alkylation Cascade

2021 ◽  
Author(s):  
◽  
Matthew Fisk
Keyword(s):  
Organic Synthesis ◽  
Chemical Reactions ◽  
Heterocyclic Ring ◽  
Cascade Reactions ◽  
Major Product ◽  
Complex Mixtures ◽  
Allylic Alkylation ◽  
Reaction Conditions ◽  
Ring Systems

<p>The design and development of new chemical reactions is crucial for progress in organic synthesis research. Cascade reactions, involving two or more steps carried out in situ in a single pot, provide a step-efficient and atom-economic route to synthesise polycyclic ring systems. The synthesis of new heterocyclic ring systems provides valuable routes towards complex natural products. Previous work in the Harvey group led to the development of a regioselective palladium-catalysed allylic alkylation (Pd-AA) cascade. This research aims to expand the scope and utility of this existing Pd-AA cascade, by optimising the current reaction conditions and exploring a range of non-symmetric pyran-based bis-electrophiles and nitrogen and sulfur-based β-carbonyl bis-nucleophiles.  Isomeric 2,3-unsaturated silyl glycosides based on D-glucose and D-galactose were successfully synthesised. These substrates were assessed as bis-electrophiles in the Pd-AA cascade. The yield of the cascade was successfully optimised with the glucose-derived substrate 4-hydroxy-6-methylpyran-2-one, using Pd₂(dba)₃ and Xantphos, to 87% from the previously reported 77% yield. However, the galactose-derived silyl glycoside formed an undesired pyranone as the major product. Additionally, a series of β-dicarbonyl compounds (4-hydroxy-6-methylpyran-2-one analogues) were assessed as bis-nucleophiles in the Pd-AA cascade, with all of the analogues forming complex mixtures of side products and a fully unsaturated pyranone as the major isolated product.</p>

scholarly journals Optimisation and Scope of a Palladium-Catalysed Allylic Alkylation Cascade

2021 ◽  
Author(s):  
◽  
Matthew Fisk
Keyword(s):  
Organic Synthesis ◽  
Chemical Reactions ◽  
Heterocyclic Ring ◽  
Cascade Reactions ◽  
Major Product ◽  
Complex Mixtures ◽  
Allylic Alkylation ◽  
Reaction Conditions ◽  
Ring Systems

<p>The design and development of new chemical reactions is crucial for progress in organic synthesis research. Cascade reactions, involving two or more steps carried out in situ in a single pot, provide a step-efficient and atom-economic route to synthesise polycyclic ring systems. The synthesis of new heterocyclic ring systems provides valuable routes towards complex natural products. Previous work in the Harvey group led to the development of a regioselective palladium-catalysed allylic alkylation (Pd-AA) cascade. This research aims to expand the scope and utility of this existing Pd-AA cascade, by optimising the current reaction conditions and exploring a range of non-symmetric pyran-based bis-electrophiles and nitrogen and sulfur-based β-carbonyl bis-nucleophiles.  Isomeric 2,3-unsaturated silyl glycosides based on D-glucose and D-galactose were successfully synthesised. These substrates were assessed as bis-electrophiles in the Pd-AA cascade. The yield of the cascade was successfully optimised with the glucose-derived substrate 4-hydroxy-6-methylpyran-2-one, using Pd₂(dba)₃ and Xantphos, to 87% from the previously reported 77% yield. However, the galactose-derived silyl glycoside formed an undesired pyranone as the major product. Additionally, a series of β-dicarbonyl compounds (4-hydroxy-6-methylpyran-2-one analogues) were assessed as bis-nucleophiles in the Pd-AA cascade, with all of the analogues forming complex mixtures of side products and a fully unsaturated pyranone as the major isolated product.</p>

scholarly journals A Palladium-Catalysed Allylic Alkylation Cascade: Towards the Total Synthesis of Thromboxanes A₂ and B₂

2021 ◽  
Author(s):  
◽  
Claire Alison Turner
Keyword(s):  
Total Synthesis ◽  
Organic Synthesis ◽  
Chemical Reactions ◽  
Allylic Alkylation ◽  
One Pot ◽  
Stereochemical Assignment ◽  
Leaving Group ◽  
Unsaturated Lactones ◽  
Hydrolysis Of ◽  
C Nmr

<p>The design and development of new chemical reactions is crucial to the ongoing success of organic synthesis research. In this work the scope and utility of a recently discovered regioselective palladium-catalysed allylic alkylation (Pd-AA) cascade was explored through increasing the range of non-symmetric pyran-based biselectrophiles and β-dicarbonyl bis-nucleophiles that can be used in this reaction.  Four differentially protected tri-substituted dihydropyrans based on glucose were synthesised, including 2,3-unsaturated silyl glycosides and α,β-unsaturated lactones. These substrates were assessed as bis-electrophiles in the Pd-AA cascade. One silyl glycoside bis-electrophile, possessing a carbonate leaving group, was shown to be an excellent substrate for reaction with a number of cyclic bis-nucleophiles. Furthermore, a series of regioisomeric methylated 4-hydroxycoumarins were synthesised, tested and found to be equally effective as bis-nucleophiles in the Pd-AA cascade with both acyclic and cyclic bis-electrophiles.  Advances made during this research include a novel Ferrier reaction with silanol nucleophiles, which was found to produce silyl glycosides, albeit in low yields. Additionally, several Perlin aldehydes were generated by the Ferrier-type hydrolysis of 3,4,6-tri-O-acetyl-D-glucal and led to the discovery of discrepant structural assignments in the literature. Furthermore, a ¹³C NMR shielding template was generated as a tool for the stereochemical assignment of tri-substituted dihydropyrans.  An extended variant of the Pd-AA cascade was achieved by employment of the bisnucleophile Meldrum’s acid with the optimal tri-substituted bis-electrophile in the presence of H₂O. The reaction afforded a γ-butyrolactone that could serve as a potential intermediate en route to the synthesis of the biologically interesting compounds thromboxanes A₂ and B₂. This extended Pd-AA cascade, although currently unoptimised, is capable of performing five synthetic transformations in one-pot and holds the potential to improve on the current syntheses of the thromboxanes.</p>

Multicomponent Cascade Reactions:  Sequential [1 + 4] and [2 + 3] Cycloadditions for the Generation of Heterocyclic Ring Systems

2005 ◽  
Vol 7 (15) ◽  
pp. 3179-3182 ◽  
Author(s):  
Nicolas M. Fédou ◽  
Philip J. Parsons ◽  
Eddy M. E. Viseux ◽  
Alan J. Whittle
Keyword(s):  
Heterocyclic Ring ◽  
Cascade Reactions ◽  
Ring Systems

scholarly journals A Palladium-Catalysed Allylic Alkylation Cascade: Towards the Total Synthesis of Thromboxanes A₂ and B₂

2021 ◽  
Author(s):  
◽  
Claire Alison Turner
Keyword(s):  
Total Synthesis ◽  
Organic Synthesis ◽  
Chemical Reactions ◽  
Allylic Alkylation ◽  
One Pot ◽  
Stereochemical Assignment ◽  
Leaving Group ◽  
Unsaturated Lactones ◽  
Hydrolysis Of ◽  
C Nmr

<p>The design and development of new chemical reactions is crucial to the ongoing success of organic synthesis research. In this work the scope and utility of a recently discovered regioselective palladium-catalysed allylic alkylation (Pd-AA) cascade was explored through increasing the range of non-symmetric pyran-based biselectrophiles and β-dicarbonyl bis-nucleophiles that can be used in this reaction.  Four differentially protected tri-substituted dihydropyrans based on glucose were synthesised, including 2,3-unsaturated silyl glycosides and α,β-unsaturated lactones. These substrates were assessed as bis-electrophiles in the Pd-AA cascade. One silyl glycoside bis-electrophile, possessing a carbonate leaving group, was shown to be an excellent substrate for reaction with a number of cyclic bis-nucleophiles. Furthermore, a series of regioisomeric methylated 4-hydroxycoumarins were synthesised, tested and found to be equally effective as bis-nucleophiles in the Pd-AA cascade with both acyclic and cyclic bis-electrophiles.  Advances made during this research include a novel Ferrier reaction with silanol nucleophiles, which was found to produce silyl glycosides, albeit in low yields. Additionally, several Perlin aldehydes were generated by the Ferrier-type hydrolysis of 3,4,6-tri-O-acetyl-D-glucal and led to the discovery of discrepant structural assignments in the literature. Furthermore, a ¹³C NMR shielding template was generated as a tool for the stereochemical assignment of tri-substituted dihydropyrans.  An extended variant of the Pd-AA cascade was achieved by employment of the bisnucleophile Meldrum’s acid with the optimal tri-substituted bis-electrophile in the presence of H₂O. The reaction afforded a γ-butyrolactone that could serve as a potential intermediate en route to the synthesis of the biologically interesting compounds thromboxanes A₂ and B₂. This extended Pd-AA cascade, although currently unoptimised, is capable of performing five synthetic transformations in one-pot and holds the potential to improve on the current syntheses of the thromboxanes.</p>

Engineering Enzymes and Antibodies

MRS Bulletin ◽  
1992 ◽  
Vol 17 (11) ◽  
pp. 48-52
Author(s):  
Donald Hilvert
Keyword(s):  
Natural Products ◽  
Organic Synthesis ◽  
Chemical Reactions ◽  
Food Additives ◽  
Diels Alder ◽  
Fine Chemicals ◽  
Reaction Conditions ◽  
Natural Enzyme ◽  
Commercial Applications ◽  
Substrate Concentrations

Phenomenal rate accelerations, exacting selectivities, and mild reaction conditions characterize biocatalysis and have generated considerable interest in nonbiological applications of enzymes. As a result of greater availability and purity, these molecules are now being used increasingly in organic synthesis to prepare complex natural products and novel materials. They are also being exploited industrially in the production of food additives, pharmaceuticals, and fine chemicals.Unfortunately, for many commercial applications, natural enzymes may be unsuitable. They may be unstable or difficult to isolate; they may function poorly at the temperatures, pH's, and substrate concentrations needed for reaction; or they may lack appropriate specificity. For many chemical reactions, a natural enzyme may not even exist. For example, natural biocatalysts for the synthetically valuable Diels-Alder cycloaddition have yet to be discovered.

Synthesis of 3,3-Dialkylated Oxindoles by Oxidative Radical 1,2-Alkylarylation of α,β-Unsaturated Amides

Synlett ◽  
2017 ◽  
Vol 28 (11) ◽  
pp. 1244-1249 ◽  
Author(s):  
Joyram Guin ◽  
Promita Biswas ◽  
Subhasis Paul
Keyword(s):  
Drug Discovery ◽  
Organic Synthesis ◽  
Alkyl Radical ◽  
Cascade Reactions ◽  
Reaction Conditions ◽  
Important Place ◽  
Alkyl Radicals ◽  
Stereogenic Centers ◽  
Activated Olefins ◽  
Quaternary Stereogenic Centers

3,3-Dialkylated oxindoles (1,3-dihydro-2H-indol-2-ones), particularly those containing C3 quaternary stereogenic centers, occupy an important place in organic synthesis and drug discovery. The radical 1,2-alkylarylation of activated olefins with alkyl radicals has emerged as the most atom- and step-economical approach to 3,3-dialkylated oxindoles. This article covers important developments in the area of oxidative radical alkylation/cyclization cascade reactions of α,β-unsaturated amides toward the synthesis of alkyl-substituted oxindoles by employing a range of alkyl-radical precursors and various reaction conditions.

scholarly journals Multicomponent Cascade Reactions: Sequential [1 + 4] and [2 + 3] Cycloadditions for the Generation of Heterocyclic Ring Systems.

ChemInform ◽  
2005 ◽  
Vol 36 (48) ◽  
Author(s):  
Nicolas M. Fedou ◽  
Philip J. Parsons ◽  
Eddy M. E. Viseux ◽  
Alan J. Whittle
Keyword(s):  
Heterocyclic Ring ◽  
Cascade Reactions ◽  
Ring Systems

Urea-Catalyzed Functionalization of Unactivated C–H Bonds

2020 ◽  
Author(s):  
Alex L. Bagdasarian ◽  
Stasik Popov ◽  
Benjamin Wigman ◽  
Wenjing Wei ◽  
woojin lee ◽  
...  
Keyword(s):  
Hydrogen Bonding ◽  
Organic Synthesis ◽  
High Energy ◽  
Acid Catalysts ◽  
Potential Utility ◽  
New Paradigm ◽  
Lewis Acid Catalysts ◽  
Reaction Conditions ◽  
Highly Active ◽  
Acidic Nature

Herein we report the 3,5bistrifluoromethylphenyl urea-catalyzed functionalization of unactivated C–H bonds. In this system, the urea catalyst mediates the formation of high-energy vinyl carbocations that undergo facile C–H insertion and Friedel–Crafts reactions. We introduce a new paradigm for these privileged scaffolds where the combination of hydrogen bonding motifs and strong bases affords highly active Lewis acid catalysts capable of ionizing strong C–O bonds. Despite the highly Lewis acidic nature of these catalysts that enables triflate abstraction from sp<sup>2</sup> carbons, these newly found reaction conditions allow for the formation of heterocycles and tolerate highly Lewis basic heteroaromatic substrates. This strategy showcases the potential utility of dicoordinated vinyl carbocations in organic synthesis.<br>

Urea-Catalyzed Functionalization of Unactivated C–H Bonds

2020 ◽  
Author(s):  
Alex L. Bagdasarian ◽  
Stasik Popov ◽  
Benjamin Wigman ◽  
Wenjing Wei ◽  
woojin lee ◽  
...  
Keyword(s):  
Hydrogen Bonding ◽  
Organic Synthesis ◽  
High Energy ◽  
Acid Catalysts ◽  
Potential Utility ◽  
New Paradigm ◽  
Lewis Acid Catalysts ◽  
Reaction Conditions ◽  
Highly Active ◽  
Acidic Nature

Herein we report the 3,5bistrifluoromethylphenyl urea-catalyzed functionalization of unactivated C–H bonds. In this system, the urea catalyst mediates the formation of high-energy vinyl carbocations that undergo facile C–H insertion and Friedel–Crafts reactions. We introduce a new paradigm for these privileged scaffolds where the combination of hydrogen bonding motifs and strong bases affords highly active Lewis acid catalysts capable of ionizing strong C–O bonds. Despite the highly Lewis acidic nature of these catalysts that enables triflate abstraction from sp<sup>2</sup> carbons, these newly found reaction conditions allow for the formation of heterocycles and tolerate highly Lewis basic heteroaromatic substrates. This strategy showcases the potential utility of dicoordinated vinyl carbocations in organic synthesis.<br>

A Mild and Simple Method for Making MIDA Boronates

2020 ◽  
Author(s):  
Aidan Kelly ◽  
Peng-Jui (Ruby) Chen ◽  
Jenna Klubnick ◽  
Daniel J. Blair ◽  
Martin D. Burke
Keyword(s):  
Organic Synthesis ◽  
Boronic Acids ◽  
Simple Method ◽  
Direct Preparation ◽  
Synthesis Procedure ◽  
Harsh Conditions

<div> <div> <div> <p>Existing methods for making MIDA boronates require harsh conditions and complex procedures to achieve dehydration. Here we disclose that a pre-dried form of MIDA, MIDA anhydride, acts as both a source of the MIDA ligand and an in situ desiccant to enable a mild and simple MIDA boronate synthesis procedure. This method expands the range of sensitive boronic acids that can be converted into their MIDA boronate counterparts. Further utilizing unique properties of MIDA boronates, we have developed a MIDA Boronate Maker Kit which enables the direct preparation and purification of MIDA boronates from boronic acids using only heating and centrifuge equipment that is widely available in labs that do not specialize in organic synthesis. </p> </div> </div> </div>

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