370-84-3

Upstream product

• 114-70-5 sodium phenylacetate 
• 103-80-0 phenylacetyl chloride 
• 103-82-2 phenylacetic acid 
• 536-74-3 phenylacetylene 
• 122-78-1 phenylacetaldehyde 
• 201230-82-2 carbon monoxide 
• 100-39-0 benzyl bromide 
• 134918-41-5 epoxide of α,β,β-trifluorostyrene 
• 134918-42-6 epoxide of α,β-difluoro-β-chlorostyrene 
• 100-44-7 benzyl chloride 
• 60-12-8 2-phenylethanol 
• 64325-22-0 1,2-Difluoro-1-lithio-2-phenylethene 
• 447-14-3 1,2,2-trifluorostyrene 
• 88641-55-8 tetrabutylammonium chloride monohydrate 

Downstream Products

• 103-82-2 phenylacetic acid 
• 220329-90-8 (S)-2-[(S)-1-((S)-2-Oxo-1-phenyl-2-pyrrolidin-1-yl-ethyl)-allyl]-pyrrolidine-1-carboxylic acid tert-butyl ester 
• 102-16-9 benzyl 2-phenylacetate 
• 7500-45-0 N-benzylphenylacetamide 
• 40155-10-0 (3S,5S,7S)-adamantan-1-yl 2-phenylacetate 

Relevant academic research and scientific papers

Gram-Scale Preparation of Acyl Fluorides and Their Reactions with Hindered Nucleophiles

A series of acyl fluorides was synthesized at 100 mmol scale using phase-transfer-catalyzed halogen exchange between acyl chlorides and aqueous bifluoride solution. The convenient procedure consists of vigorous stirring of the biphasic mixture at room temperature, followed by extraction and distillation. Isolated acyl fluorides (usually 7-20 g) display excellent purity and can be transformed into sterically hindered amides and esters when treated with lithium amide bases and alkoxides under mild conditions.

Metal-free approach for hindered amide-bond formation with hypervalent iodine(iii) reagents: application to hindered peptide synthesis

A new bio-inspired approach is reported for amide and peptide synthesis using α-amino esters that possess a potential activating group (PAG) at the ester residue. To activate the ester functionality under mild metal-free conditions, we exploited the facile dearomatization of phenols with hypervalent iodine(iii) reagents. Using a pyridine-hydrogen fluoride complex, highly reactive acyl fluoride intermediates can be successfully generated, thereby allowing for the smooth formation of sterically hindered amides and peptides from bulky amines and α-amino esters, respectively.

Efficient cleavage of tertiary amide bonds: Via radical-polar crossover using a copper(ii) bromide/Selectfluor hybrid system

A novel approach for the efficient cleavage of the amide bonds in tertiary amides is reported. Based on the selective radical abstraction of a benzylic hydrogen atom by a CuBr2/Selectfluor hybrid system followed by a selective cleavage of an N-C bond, an acyl fluoride intermediate is formed. This intermediate may then be derivatized in a one-pot fashion. The reaction proceeds under mild conditions and exhibits a broad substrate scope with respect to the tertiary amide moiety as well as to nitrogen, oxygen, and carbon nucleophiles for the subsequent derivatization. Mechanistic studies suggest that the present reaction proceeds via a radical-polar crossover process that involves benzylic carbon radicals generated by the selective radical abstraction of a benzylic hydrogen atom by the CuBr2/Selectfluor hybrid system. Furthermore, a synthetic application of this method for the selective cleavage of peptides is described. This journal is

Direct Access to Acyl Fluorides from Carboxylic Acids Using a Phosphine/Fluoride Deoxyfluorination Reagent System

A fast and simple method for deoxyfluorination of carboxylic acids is presented. The protocol employs commodity chemicals (PPh3, NBS, fluoride), affording products in excellent yields under mild conditions. Acyloxyphosphonium ion, the key reaction intermediate, was identified by NMR spectroscopic methods. Br?nsted acidic conditions are essential for efficient C-F bond formation. The protocol displays scalability, high functional group tolerance, chemoselectivity, and easy purification of products. Deoxyfluorination of active pharmaceutical ingredients was established.

High-throughput evaluation of in situ-generated cobalt(III) catalysts for acyl fluoride synthesis

Using a high-throughput experimental procedure, a series of cobalt(iii) complexes of the general formula CpRCo(I)(X)(L) were prepared and screened for their activity towards the catalytic nucleophilic fluorination of benzoyl chloride. A highly active catalyst was identified, and successfully employed in a mild and effective protocol for the synthesis of a group of acyl fluoride compounds.

FORMATION OF BONDS BY OUTER-SPHERE OXIDATIVE ELECTROPHILIC FLUORINATION

There is described a method of fluorination of an alkenyl, alkynyl, aryl or isonitrile compound which comprises reacting an alkenyl, alkynyl, aryl or isonitrile compound with a metal-mediated outer-sphere electrophilic fluorinating (OSEF) agent.

Access to novel fluorovinylidene ligands via exploitation of outer-sphere electrophilic fluorination: New insights into C-F bond formation and activation

Metal vinylidene complexes are widely encountered, or postulated, as intermediates in a range of important metal-mediated transformations of alkynes. However, fluorovinylidene complexes have rarely been described and their reactivity is largely unexplored. By making use of the novel outer-sphere electrophilic fluorination (OSEF) strategy we have developed a rapid, robust and convenient method for the preparation of fluorovinylidene and trifluoromethylvinylidene ruthenium complexes from non-fluorinated alkynes. Spectroscopic investigations (NMR and UV/Vis), coupled with TD-DFT studies, show that fluorine incorporation results in significant changes to the electronic structure of the vinylidene ligand. The reactivity of fluorovinylidene complexes shows many similarities to non-fluorinated analogues, but also some interesting differences, including a propensity to undergo unexpected C-F bond cleavage reactions. Heating fluorovinylidene complex [Ru(η5-C5H5)(PPh3)2(CC{F}R)][BF4] led to C-H activation of a PPh3 ligand to form an orthometallated fluorovinylphosphonium ligand. Reaction with pyridine led to nucleophilic attack at the metal-bound carbon atom of the vinylidene to form a vinyl pyridinium species, which undergoes both C-H and C-F activation to give a novel pyridylidene complex. Addition of water, in the presence of chloride, leads to anti-Markovnikov hydration of a fluorovinylidene complex to form an α-fluoroaldehyde, which slowly rearranges to its acyl fluoride isomer. Therefore, fluorovinylidenes ligands may be viewed as synthetic equivalents of 1-fluoroalkynes providing access to reactivity not possible by other routes.

A convenient, one-pot procedure for the preparation of acyl and sulfonyl fluorides using Cl3CCN, Ph3P, and TBAF(t -BuOH) 4

Various carboxylic acids were converted into acyl fluorides in excellent yields by treatment with trichloroacetonitrile, triphenylphosphine, and TBAF(t-BuOH)4 at room temperature. The reaction was applicable to the preparation of acid-sensitive amino acid fluorides without deprotection or rearrangement

Reactions of alcohols with cesium fluoroxysulfate

The reactions of alcohols with cesium fluoroxysulfate (CsSO4F) in MeCN suspension were studied, and the role of the structure of the alcohol and the reaction conditions on the course of reaction was determined. Secondary benzyl alcohols bearing a nonactivating aromatic ring were selectively oxidized to the corresponding ketones, while the CsSO4F-mediated reaction of phenyl-1-naphthylmethanol resulted in the formation of 1-fluoronaphthalene and benzaldehyde. Cyclic and noncyclic secondary alcohols were readily converted to ketones, as well as 1-hydroxybenzecyclanes to benzocyclanones- 1, without any further fluorination or oxidation under the reaction conditions. On the other hand, reactions of primary alcohols with CsSO4F resulted in the formation of acid fluorides derived from further fluorination of aldehydes. Another type of transformation was observed in the case of alcohols bearing a benzyl functional group attached geminal to a hydroxy group, where decarbanylation of reactive intermediates resulting in the formation of benzyl fluoride derivatives became the main process. 2- Phenylethanol was so converted to benzyl fluoride and phenylacetyl fluoride in a 3:1 relative ratio, while 2-phenyl-1-propanol was selectively transformed to 1-phenyl-1-fluoroethane. The presence of the radical inhibitor nitrobenzene in the reaction mixture considerably inhibited conversion of the starting material. The same effect was observed by lowering the solvent polarity. Hammett correlation analysis of the effect of substituents on the reaction rates of oxidation of a set of substituted 1-phenyl-1-ethanols to acetophenones gave the reaction constant p+ = -0.32, while analysis of analogous data for the transformations of benzyl alcohols to benzoyl fluorides gave the value of -0.54. A mechanism including radical intermediates was proposed for the transformation of alcohols by CsSO4F.

Catalytic Acid Fluoride Synthesis via Carbonylation of Organic Bromides in the Presence Potassium Fluoride

Various aryl bromides were carbonylated under an atmospheric pressure of carbon monoxide in DMF in the presence of potassium fluoride to give aroyl fluorides in excellent yields.The carbonylation was promoted by the addition of phase transfer catalysts, but the contamination with water reduced the selectivity.