scholarly journals A Ball Milling Enabled Cross-Electrophile Coupling

2021 ◽  
Author(s):  
Andrew Jones ◽  
William I. Nicholson ◽  
Jamie Leitch ◽  
Duncan Browne
Keyword(s):  
Ball Milling ◽  
Bond Formation ◽  
Reaction Times ◽  
Building Blocks ◽  
Mechanical Action ◽  
Catalytic Cycle ◽  
Moisture Sensitive ◽  
Pseudo Halides ◽  
Zinc Sources

<div><div><div><p>The nickel-catalyzed cross-electrophile coupling of aryl (pseudo)halides and alkyl (pseudo)halides enabled by ball-milling is herein described. Under a mechanochemical manifold, the reductive C–C bond formation was achieved in the absence of bulk solvent and air/moisture sensitive set-ups, in reaction times of 2 hours. The mechanical action provided by ball milling permits the use of a range of zinc sources to turnover the catalytic cycle of nickel. A library of 28 cross- electrophile coupled building blocks has been constructed to exemplify this technique.</p></div></div></div>

scholarly journals A Ball Milling Enabled Cross-Electrophile Coupling

2021 ◽  
Author(s):  
Andrew Jones ◽  
William I. Nicholson ◽  
Jamie Leitch ◽  
Duncan Browne
Keyword(s):  
Ball Milling ◽  
Bond Formation ◽  
Reaction Times ◽  
Building Blocks ◽  
Mechanical Action ◽  
Catalytic Cycle ◽  
Moisture Sensitive ◽  
Pseudo Halides ◽  
Zinc Sources

<div><div><div><p>The nickel-catalyzed cross-electrophile coupling of aryl (pseudo)halides and alkyl (pseudo)halides enabled by ball-milling is herein described. Under a mechanochemical manifold, the reductive C–C bond formation was achieved in the absence of bulk solvent and air/moisture sensitive set-ups, in reaction times of 2 hours. The mechanical action provided by ball milling permits the use of a range of zinc sources to turnover the catalytic cycle of nickel. A library of 28 cross- electrophile coupled building blocks has been constructed to exemplify this technique.</p></div></div></div>

scholarly journals Atom-Economical Cross-Coupling of Internal and Terminal Alkynes to Access 1,3-Enynes

2020 ◽  
Author(s):  
Mingyu Liu ◽  
Tianhua Tang ◽  
Omar Apolinar ◽  
Rei Matsuura ◽  
Carl Busacca ◽  
...  
Keyword(s):  
Chemical Synthesis ◽  
Large Scale ◽  
Bond Formation ◽  
Cross Coupling ◽  
Building Blocks ◽  
Commercial Production ◽  
Catalytic Cycle ◽  
Catalyst Loading ◽  
Terminal Alkynes ◽  
Catalytic Method

Selective carbon–carbon (C–C) bond formation in chemical synthesis generally requires pre-functionalized building blocks. However, the requisite pre-functionalization steps undermine the efficiency of multi-step synthetic sequences, which is particularly problematic in large-scale applications, such as in the commercial production of pharmaceuticals. Herein, we describe a selective and catalytic method for synthesizing 1,3-enynes without pre-functionalized building blocks. This method is facilitated by a tailored P,N-ligand that enables regioselective coupling and suppresses secondary <i>E</i>/<i>Z</i>-isomerization of the product. The transformation enables several classes of unactivated internal acceptor alkynes to be coupled with terminal donor alkynes to deliver 1,3-enynes in a highly regio- and stereoselective manner. The scope of compatible acceptor alkynes includes propargyl alcohols, (homo)propargyl amine derivatives, and (homo)propargyl carboxamides. The reaction is scalable and can operate effectively with 0.5 mol% catalyst loading. The products are versatile intermediates that can participate in various downstream transformations. We also present preliminary mechanistic experiments that are consistent with a redox-neutral Pd(II) catalytic cycle.

scholarly journals Atom-Economical Cross-Coupling of Internal and Terminal Alkynes to Access 1,3-Enynes

2020 ◽  
Author(s):  
Mingyu Liu ◽  
Tianhua Tang ◽  
Omar Apolinar ◽  
Rei Matsuura ◽  
Carl Busacca ◽  
...  
Keyword(s):  
Chemical Synthesis ◽  
Large Scale ◽  
Bond Formation ◽  
Cross Coupling ◽  
Building Blocks ◽  
Commercial Production ◽  
Catalytic Cycle ◽  
Catalyst Loading ◽  
Terminal Alkynes ◽  
Catalytic Method

Selective carbon–carbon (C–C) bond formation in chemical synthesis generally requires pre-functionalized building blocks. However, the requisite pre-functionalization steps undermine the efficiency of multi-step synthetic sequences, which is particularly problematic in large-scale applications, such as in the commercial production of pharmaceuticals. Herein, we describe a selective and catalytic method for synthesizing 1,3-enynes without pre-functionalized building blocks. This method is facilitated by a tailored P,N-ligand that enables regioselective coupling and suppresses secondary <i>E</i>/<i>Z</i>-isomerization of the product. The transformation enables several classes of unactivated internal acceptor alkynes to be coupled with terminal donor alkynes to deliver 1,3-enynes in a highly regio- and stereoselective manner. The scope of compatible acceptor alkynes includes propargyl alcohols, (homo)propargyl amine derivatives, and (homo)propargyl carboxamides. The reaction is scalable and can operate effectively with 0.5 mol% catalyst loading. The products are versatile intermediates that can participate in various downstream transformations. We also present preliminary mechanistic experiments that are consistent with a redox-neutral Pd(II) catalytic cycle.

Formation of Carbon-Oxygen Bond Mediated by Hypervalent Iodine Reagents Under Metal-free Conditions

2020 ◽  
Vol 17 ◽  
Author(s):  
Ayesha Jalil ◽  
Yaxin O Yang ◽  
Zhendong Chen ◽  
Rongxuan Jia ◽  
Tianhao Bi ◽  
...  
Keyword(s):  
Natural Products ◽  
Bond Formation ◽  
Building Blocks ◽  
Review Article ◽  
Hypervalent Iodine ◽  
Metal Free ◽  
Bioactive Natural Products ◽  
The Past ◽  
Oxygen Bond ◽  
Privileged Scaffolds

: Hypervalent iodine reagents are a class of non-metallic oxidants have been widely used in the construction of several sorts of bond formations. This surging interest in hypervalent iodine reagents is essentially due to their very useful oxidizing properties, combined with their benign environmental character and commercial availability from the past few decades ago. Furthermore, these hypervalent iodine reagents have been used in the construction of many significant building blocks and privileged scaffolds of bioactive natural products. The purpose of writing this review article is to explore all the transformations in which carbon-oxygen bond formation occurred by using hypervalent iodine reagents under metal-free conditions

Iminyl-Radical-Triggered C–C Bond Cleavage of Cycloketone Oxime Derivatives: Generation of Distal Cyano-Substituted Alkyl Radicals and Their Functionalization

Synthesis ◽  
2020 ◽  
Vol 52 (11) ◽  
pp. 1585-1601 ◽  
Author(s):  
Tiebo Xiao ◽  
Lei Zhou ◽  
Hongtai Huang ◽  
Devireddy Anand
Keyword(s):  
Halogen Bond ◽  
Cyano Group ◽  
Bond Cleavage ◽  
Bond Formation ◽  
Radical Reaction ◽  
Building Blocks ◽  
Aromatic Rings ◽  
Organometallic Reagents ◽  
Alkyl Radicals ◽  
Oxime Derivatives

Alkyl nitriles are versatile building blocks in organic synthesis because the cyano group can be easily converted into other functional groups. Iminyl-radical-triggered C–C bond cleavage of cycloketone oxime­ derivatives provides a practical route to access distal cyano-substituted alkyl radicals, which has given chemists a new radical reaction platform for the synthesis of diverse alkyl nitriles. This review provides an overview of various types of radical cyanoalkylation via ring opening of cycloketone oxime derivatives.1 Introduction2 C–C Bond Formation2.1 Alkenes as Radical Acceptors2.2 Aromatic Rings as Radical Acceptors2.3 Organometallic Reagents as Radical Acceptors2.4 Cyanoalkyl-Radical-Triggered Cyclization Reactions2.5 Miscellaneous3 C–Heteroatom Bond Formation3.1 C–O Bond Formation3.2 C–N Bond Formation3.3 C–S Bond Formation3.4 C–Halogen Bond Formation3.5 C–B Bond Formation4 Conclusion

scholarly journals Synthesis of acylglycerol derivatives by mechanochemistry

2019 ◽  
Vol 15 ◽  
pp. 811-817 ◽  
Author(s):  
Karen J Ardila-Fierro ◽  
Andrij Pich ◽  
Marc Spehr ◽  
José G Hernández ◽  
Carsten Bolm
Keyword(s):  
Amino Acids ◽  
Ball Milling ◽  
Mechanochemical Synthesis ◽  
Building Blocks ◽  
Synthetic Route ◽  
Biologically Relevant ◽  
Nucleotides And Nucleosides

In recent times, many biologically relevant building blocks such as amino acids, peptides, saccharides, nucleotides and nucleosides, etc. have been prepared by mechanochemical synthesis. However, mechanosynthesis of lipids by ball milling techniques has remained essentially unexplored. In this work, a multistep synthetic route to access mono- and diacylglycerol derivatives by mechanochemistry has been realized, including the synthesis of diacylglycerol-coumarin conjugates.

scholarly journals Biocatalytic asymmetric construction of secondary and tertiary fluorides from β-fluoro-α-ketoacids

2021 ◽  
Author(s):  
Jason Fang ◽  
Laura Turner ◽  
Michelle Chang
Keyword(s):  
Asymmetric Synthesis ◽  
Kinetic Resolution ◽  
Bond Formation ◽  
Aldol Reaction ◽  
Building Blocks ◽  
Critical Element ◽  
Type Ii ◽  
Fluorinated Building Blocks ◽  
Reaction Proceeds ◽  
New Donors

Fluorine is a critical element for the design of bioactive compounds, but its incorporation with high regio- and stereoselectivity using environmentally friendly reagents and catalysts remains an area of development. Stereogenic tertiary fluorides pose a particular synthetic challenge and are thus present in only a few approved pharmaceuticals such as fluticasone, solithromycin, and sofosbuvir. The aldol reaction of fluorinated donors provides an atom-economical approach to asymmetric C-F motifs via C-C bond formation. Here we report that the type II pyruvate aldolase HpcH and engineered mutants thereof are biocatalysts for carboligation of ß-fluoro-α-ketoacids (including fluoropyruvate, ß-fluoro-α-ketobutyrate, and ß-fluoro-α-ketovalerate) with many diverse aldehydes. The reaction proceeds with kinetic resolution in the case of racemic donors. The reactivity of HpcH towards these new donors, which are non-native in both steric and electronic properties, grants access to enantiopure fragments with secondary or tertiary fluoride stereocenters. In addition to representing the first asymmetric synthesis of tertiary fluorides via biocatalytic carboligation, the afforded products could improve the diversity of fluorinated building blocks and enable the synthesis of fluorinated drug analogs.

scholarly journals Modern Methods for the Sustainable Synthesis of Metalloporphyrins

Molecules ◽  
2021 ◽  
Vol 26 (21) ◽  
pp. 6652
Author(s):  
Carla Gomes ◽  
Mariana Peixoto ◽  
Marta Pineiro
Keyword(s):  
Metal Salt ◽  
Reaction Times ◽  
Good Alternative ◽  
Mechanical Action ◽  
Palladium Complexes ◽  
Water Soluble ◽  
Efficient Manner ◽  
Rational Development ◽  
High Yields ◽  
Adequate Method

Metalloporphyrins are involved in many and diverse applications that require the preparation of these compounds in an efficient manner, which nowadays, also involves taking into consideration sustainability issues. In this context, we use ball milling mechanochemistry and sonochemistry for the rational development of synthetic strategies for the sustainable preparation of metalloporphyrins. Zinc, copper, cobalt and palladium complexes of hydrophobic porphyrins were obtained in high yields and under mechanical action with a moderate excess of the metal salt, without any solvent or additive. Sonochemistry prove to be a good alternative for the preparation of metal complexes of water-soluble porphyrins in good yields and short reaction times. Both strategies have good sustainability scores, close to the ideal values, which is useful in comparing and helping to choose the more adequate method.

scholarly journals Biocatalytic oxidative cross-coupling reactions for biaryl bond formation

2021 ◽  
Author(s):  
Lara Zetzsche ◽  
Jessica Yazarians ◽  
Suman Chakrabarty ◽  
Meagan Hinze ◽  
April Lukowski ◽  
...  
Keyword(s):  
Asymmetric Catalysis ◽  
Bond Formation ◽  
Cross Coupling ◽  
Building Blocks ◽  
Coupling Reactions ◽  
Cytochrome P450 Enzymes ◽  
Cross Coupling Reactions ◽  
Site Selectivity ◽  
Valuable Compounds ◽  
Selective Process

Despite their varied purposes, many indispensable molecules in medicine, materials, and asymmetric catalysis share a biaryl core. The necessity of joining arene building blocks to access these valuable compounds has inspired multiple approaches for biaryl bond formation and challenged chemists to develop increasingly concise and robust methods for this task. Oxidative coupling of two C–H bonds offers an efficient strategy for the formation of a biaryl C–C bond, however, fundamental challenges remain in controlling the reactivity and selectivity for uniting a given pair of substrates. Biocatalytic oxidative cross-coupling reactions have the potential to overcome limitations inherent to small molecule- mediated methods by providing a paradigm with catalyst-controlled selectivity. In this article, we disclose a strategy for biocatalytic cross-coupling through oxidative C–C bond formation using cytochrome P450 enzymes. We demonstrate the ability to catalyze cross-coupling reactions on a panel of phenolic substrates using natural P450 catalysts. Moreover, we engineer a P450 to possess the desired reactivity, site- selectivity, and atroposelectivity by transforming a low-yielding, unselective reaction into a highly efficient and selective process. This streamlined method for constructing sterically hindered biaryl bonds provides a programmable platform for assembling molecules with catalyst-controlled reactivity and selectivity.

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