HFIP in Organic Synthesis

Chemical Reviews, Год журнала: 2022, Номер 122(15), С. 12544 - 12747

Опубликована: Июль 17, 2022

1,1,1,3,3,3-Hexafluoroisopropanol (HFIP) is a polar, strongly hydrogen bond-donating solvent that has found numerous uses in organic synthesis due to its ability stabilize ionic species, transfer protons, and engage range of other intermolecular interactions. The use this exponentially increased the past decade become choice some areas, such as C–H functionalization chemistry. In review, following brief history HFIP an overview physical properties, literature examples reactions using or additive are presented, emphasizing effect each reaction.

Язык: Английский

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Attenuating N‐Oxyl Decomposition for Improved Hydrogen Atom Transfer Catalysts

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(21)

Опубликована: Март 4, 2024

Abstract The design of N ‐oxyl hydrogen atom transfer catalysts has proven challenging to date. Previous efforts have focused on the functionalization archetype, phthalimide‐ ‐oxyl. Driven in part by limited options for modification this structure, strategy provided only modest improvements reactivity and/or solubility. Our previous mechanistic suggested that while electron‐withdrawing carbonyls phthalimide are necessary maximize O−H bond dissociation enthalpy HAT product hydroxylamine and overall reaction thermodynamics, they undergo nucleophilic substitution leading catalyst decomposition. In an attempt minimize vulnerability, we report characterization wherein aryl ring PINO is replaced with combination a substituted heteroatom quaternary carbon. By rendering one carbonyl carbon less electrophilic other sterically accessible, corresponding 1 ‐aryl‐hydantoin‐ 3 radical showed significantly higher stability than as well improvement reactivity. This proof‐of‐principle new scaffold may accelerate future discovery development.

Язык: Английский

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Organocatalytic Enantioselective [4+3]‐Cycloadditions of Azaoxyallyl Cations with 2‐Aminophenyl Enones

Advanced Synthesis & Catalysis, Год журнала: 2021, Номер 363(17), С. 4197 - 4203

Опубликована: Июль 12, 2021

Abstract The first organocatalytic asymmetric [4+3]‐cycloaddition of 2‐aminophenyl α,β‐unsaturated carbonyls with in situ generated azaoxyallyl cations was developed, and enantioenriched functionalized seven‐membered 1,4‐benzodiazepine‐3‐ones were obtained good yields excellent enantioselectivities. This approach also extended to the δ‐hydroxy carbonyls, affording 1,4‐oxazepanes one step under mild conditions. Several novel adducts demonstrated promising bioactivity prevention peripheral nerve degeneration. magnified image

Язык: Английский

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Heteroannulation of Arynes with α-Bromodifluorohydroxamates: An Efficient and General Approach to Access 2,2-Difluoro Indoxyls

Organic Letters, Год журнала: 2024, Номер 26(27), С. 5682 - 5688

Опубликована: Июнь 27, 2024

Herein, we report the first general approach to access

Язык: Английский

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α‐Halocarbonyls as a Valuable Functionalized Tertiary Alkyl Source

ChemistryOpen, Год журнала: 2024, Номер unknown

Опубликована: Июль 11, 2024

Abstract This review introduces the synthetic organic chemical value of α‐bromocarbonyl compounds with tertiary carbons. compound a carbon has been used primarily only as radical initiator in atom transfer polymerization (ATRP) reactions. However, recent development photo‐radical reactions (around 2010), research on use alkyl precursors became popular 2012). As more examples were reported, studied not radicals but also for their applications organometallic and ionic That is, act nucleophiles well electrophiles. The carbonyl group is attractive because it allows skeleton to be converted after reaction, being applied total synthesis. In our survey until 2022, can perform full range necessary synthesis, including multi‐component reactions, cross‐coupling, substitution, cyclization, rearrangement, stereospecific asymmetric α‐Bromocarbonyl have created new trend alkylation, which then had limited reaction patterns focuses how chemistry.

Язык: Английский

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Aza‐oxyallyl Cations and Their Applications in (3+m) Cycloaddition Reactions

European Journal of Organic Chemistry, Год журнала: 2022, Номер 2022(47)

Опубликована: Окт. 10, 2022

Abstract Aza‐oxyallyl cations, as proposed by Sheehan in the 1960s have garnered significant attention among synthetic organic community, owing to their diverse reactivity profile for constructing N‐scaffolds of biological interest. During its initial growth, aza‐oxyallyl cations were used effectively a 3‐unit synthon 1,3 dipoles create N‐heterocycles via cycloaddition reactions, wherein cation served electrophilic counterpart. Recently, new variations been reported, including usage 1,4 dipole domino and unique alkylating ability heteroatoms. This review article provides an update recent developments this area prevailing mechanistic insight.

Язык: Английский

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Heteroarylation of Congested α-Bromoamides with Imidazo-Heteroarenes and Indolizines via Aza-Oxyallyl Cations: Enroute to Dibenzoazepinone and Zolpidem Analogues

The Journal of Organic Chemistry, Год журнала: 2022, Номер 87(21), С. 14168 - 14176

Опубликована: Окт. 19, 2022

Herein, we report a highly efficient and unprecedented approach for heteroarylation of congested α-bromoamides via electrophilic aromatic substitution imidazo-heteroarenes indolizines under mild reaction conditions (room temperature, metal, oxidant free). The participation an in situ generated aza-oxyallyl cation as alkylating agent is the hallmark this transformation. method was readily adapted to synthesize novel imidazo-heteroarene-fused dibenzoazepinone architectures potential medicinal value.

Язык: Английский

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Metal-free synthesis of 1,4-benzodiazepines and quinazolinones from hexafluoroisopropyl 2-aminobenzoates at room temperature

RSC Advances, Год журнала: 2021, Номер 11(9), С. 4966 - 4970

Опубликована: Янв. 1, 2021

Herein, we describe the novel reactivity of hexafluoroisopropyl 2-aminobenzoates. The metal-free synthesis 1,4-benzodiazepines and quinazolinones from 2-aminobenzoates has been developed at room temperature. These procedures feature good functional group tolerance, mild reaction conditions, excellent yields. newly formed products can readily be converted to other useful N-heterocycles. Moreover, their derivatives showed potent anticancer activities in vitro by MTT assay.

Язык: Английский

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Aza-Oxyallyl Cation Driven 3-Amido Oxetane Rearrangement to 2-Oxazolines: Access to Oxazoline Amide Ethers

The Journal of Organic Chemistry, Год журнала: 2022, Номер 87(5), С. 2155 - 2166

Опубликована: Фев. 7, 2022

Herein, we report a highly facile and unprecedented activation of 3-amido oxetanes to synthesize 2-oxazoline amide ethers using transient electrophilic aza-oxyallyl cation as an activating well alkylating agent under mild reaction conditions. The driven intramolecular rearrangement 2-oxazolines is the hallmark this transformation new addition reactivity profile cations.

Язык: Английский

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Attenuating N-oxyl Decomposition for Improved Hydrogen Atom Transfer Catalysts Design

Опубликована: Янв. 3, 2024

The design of N-oxyl hydrogen atom transfer catalysts has proven challenging to date. Previous efforts have focused on the functionalization archetype phthalimide-N-oxyl. Driven in part by limited options for modification this structure, strategy provided only modest improvement reactivity and/or solubility. Our previous mechanistic suggested that while electron-withdrawing carbonyls phthalimide are necessary maximize O-H bond dissociation enthalpy HAT product hydroxylamine and thus overall reaction thermodynamics, they can undergo nucleophilic substitution leading catalyst decomposition. In an attempt minimize vulnerability, work replaces aryl ring PINO with combination a substituted heteroatom quaternary carbon. By rendering one carbonyl carbon less electrophilic other sterically accessible, corresponding N1-aryl-hydantoin-N3-oxyl showed significantly higher stability than as well reactivity. This proof-of-principle new scaffold may accelerate future discovery development.

Язык: Английский

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