351-59-7

Upstream product

• 621-82-9 Cinnamic acid 
• 201230-82-2 carbon monoxide 
• 588-72-7 [(E)-2-bromoethenyl]benzene 
• 103-64-0 bromostyrene 
• 50978-45-5 3-oxobenzo[d]isothiazole-2(3H)-carbaldehyde 1,1-dioxide 
• 140-10-3 (E)-3-phenylacrylic acid 
• 146691-82-9 1,3-dibromo-1,1-difluoro-3-phenylpropane 
• 1257324-44-9 4-methoxybenzyl cinnamate 
• 102-92-1 cinnamoyl chloride 
• 538-56-7 cinnamic acid anhydride 

Downstream Products

• 1279102-70-3 6,8-diphenyl-1,2,3,4,5,6-hexahydronaphthalene 
• 1279102-73-6 8-isopropyl-6-phenyl-1,2,3,4,5,6-hexahydronaphthalene 

Relevant academic research and scientific papers

Intramolecular anion effect in polyoxometalate-based organocatalysts: Reactivity enhancement and chirality transfer by a metal oxide-organic cation interaction

An α1-Dawson polyanion bearing a lateral side chain with a 4-aminopyridine end group was synthesized. This organopolyoxometalate catalyzes the addition of indenyl allyl silanes to cinnamoyl fluorides. The polyanionic framework influences the organocatalyst activity and selectivity. A moderate but nonzero chirality transfer from the chiral inorganic framework to the organic substrate was observed.

Rapid and column-free syntheses of acyl fluorides and peptides usingex situgenerated thionyl fluoride

Thionyl fluoride (SOF2) was first isolated in 1896, but there have been less than 10 subsequent reports of its use as a reagent for organic synthesis. This is partly due to a lack of facile, lab-scale methods for its generation. Herein we report a novel protocol for theex situgeneration of SOF2and subsequent demonstration of its ability to access both aliphatic and aromatic acyl fluorides in 55-98% isolated yields under mild conditions and short reaction times. We further demonstrate its aptitude in amino acid couplings, with a one-pot, column-free strategy that affords the corresponding dipeptides in 65-97% isolated yields with minimal to no epimerization. The broad scope allows for a wide range of protecting groups and both natural and unnatural amino acids. Finally, we demonstrated that this new method can be used in sequential liquid phase peptide synthesis (LPPS) to afford tri-, tetra-, penta-, and decapeptides in 14-88% yields without the need for column chromatography. We also demonstrated that this new method is amenable to solid phase peptide synthesis (SPPS), affording di- and pentapeptides in 80-98% yields.

Synthesis of N-trifluoromethyl amides from carboxylic acids

Found in biomolecules, pharmaceuticals, and agrochemicals, amide-containing molecules are ubiquitous in nature, and their derivatization represents a significant methodological goal in fluorine chemistry. Trifluoromethyl amides have emerged as important functional groups frequently found in pharmaceutical compounds. To date, there is no strategy for synthesizing N-trifluoromethyl amides from abundant organic carboxylic acid derivatives, which are ideal starting materials in amide synthesis. Here, we report the synthesis of N-trifluoromethyl amides from carboxylic acid halides and esters under mild conditions via isothiocyanates in the presence of silver fluoride at room temperature. Through this strategy, isothiocyanates are desulfurized with AgF, and then the formed derivative is acylated to afford N-trifluoromethyl amides, including previously inaccessible structures. This method shows broad scope, provides a platform for rapidly generating N-trifluoromethyl amides by virtue of the diversity and availability of both reaction partners, and should find application in the modification of advanced intermediates.

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.

Radical-Mediated Activation of Esters with a Copper/Selectfluor System: Synthesis of Bulky Amides and Peptides

Herein, we describe a new approach for the activation of esters via a radical-mediated process enabled by a copper/Selectfluor system. A variety of para-methoxybenzyl esters derived from bulky carboxylic acids and amino acids can be easily converted into the corresponding acyl fluorides, directly used in the one-pot synthesis of amides and peptides. As a proof of concept, this method was applied to the iterative formation of sterically hindered amide bonds.

Synthesis of Acyl Fluorides from Carboxylic Acids Using NaF-Assisted Deoxofluorination with XtalFluor-E

The synthesis of acyl fluorides using the deoxofluorination reaction of carboxylic acids using XtalFluor-E is described. This transformation, assisted by a catalytic amount of NaF, occurs at room temperature in EtOAc, where XtalFluor-E behaves as the activating agent and the fluoride source. A wide range of acyl fluorides were obtained in moderate to excellent yields (36-99%) after a simple filtration on a pad of silica gel. We also demonstrated that sequential deoxofluorination/amidation was possible.

Rapid synthesis of acyl fluorides from carboxylic acids with Cu(O2CCF2SO2F)2

Acyl fluorides have moderate electrophilicity and a very good balance between stability and reactivity. Utilization of acyl fluorides as versatile building blocks in transition-metal catalysis attracts fast-growing and great attention recently. Development of rapid and operationally simple synthetic methods for acyl fluorides has always been desirable. We report herein a rapid, simple and efficient acyl fluoride synthesis from carboxylic acids with Cu(O2CCF2SO2F)2 as a deoxofluorination reagent. Notably, Cu(O2CCF2SO2F)2 was readily prepared in large scale from inexpensive starting material, and previously used as a good trifluoromethylating reagent.

Halide-Accelerated Acyl Fluoride Formation Using Sulfuryl Fluoride

Herein, we report a new one-pot sequential method for SO2F2-mediated nucleophilic acyl substitution reactions starting from carboxylic acids. A mechanistic study revealed that SO2F2-mediated acid activation proceeds via the anhydride, which is then converted to the corresponding acyl fluoride. Tetrabutylammonium chloride or bromide accelerate the formation of acyl fluoride. Optimized halide-accelerated conditions were used to synthesize acyl fluorides in 30-80percent yields, and esters, amides, and thioesters in 72-96percent yields without reoptimization for each nucleophile.

Methoxylation of Acyl Fluorides with Tris(2,4,6-trimethoxyphenyl)phosphine via C-OMe Bond Cleavage under Metal-Free Conditions

Acyl fluorides are subjected to methoxylation with tris(2,4,6-trimethoxyphenyl)phosphine (TMPP) to afford the corresponding methyl esters in good to excellent yields. This transformation is featured by C(sp2)-OMe bond cleavage under metal-free conditions. Unprecedented utilization of TMPP as a methoxylating agent realized the installation of an OMe group into the desired products.

Benzoyl Fluorides as Fluorination Reagents: Reconstruction of Acyl Fluorides via Reversible Acyl C-F Bond Cleavage/Formation in Palladium Catalysis

This report describes the formation of value-added acyl fluorides by means of palladium-catalyzed acyl-exchange reactions between acyl fluorides and acid anhydrides. This method allows using a simple and commercially available acyl fluoride, benzoyl fluoride, as the fluoride source for the easy and efficient preparation of a variety of more complex acyl fluorides. The results of this study suggest that this reaction proceeds via a reversible acyl C-F bond cleavage/formation at the palladium center.