3874-54-2

Basic information

• Product Name: 4-Chloro-4'-fluorobutyrophenone
• Synonyms: 3-CHLOROPROPYL4-FLUOROPHENYLKETONE/4-CHLORO-4''-FLUOROBUTYROPHENONE;1-Butanone, 4-chloro-1-(4-fluorophenyl)-;1-(4-Fluorophenyl)-4-chloro-1-butanone;γ-Chloro-4'-fluorobutyrophenone;ω-Chloro-4'-fluorobutyrophenone;4-Chloro-4'-fluorobu;4-chloro-4-fluorophenyl ketone;1-Chloro-4-(4-fluorophenyl)-4-oxobutane
• CAS NO: 3874-54-2
• Molecular Formula: C₁₀H₁₀ClFO
• Molecular Weight: 200.64
• EINECS: 223-395-3
• Product Categories: ketone;Fluorobenzene;C10;Carbonyl Compounds;Ketones;Aromatics;Miscellaneous Reagents;API Intermediate
• Mol File: 3874-54-2.mol
• Article Data: 19

Chemical Properties

• Melting Point: 5-6 °C
• Boiling Point: 130-132 °C (0.97513 mmHg)
• Flash Point: >230 °F
• Appearance: Slightly yellow-greenish clear/Oil
• Density: 1.22 g/mL at 25 °C(lit.)
• Refractive Index: n20/D 1.5255(lit.)
• Storage Temp.: Refrigerator
• Solubility: Chloroform (Sparingly), Ethyl Acetate (Slightly), Methanol (Slightly)
• Water Solubility: 0.38 g/L (20 ºC)
• BRN: 608741
• CAS DataBase Reference: 4-Chloro-4'-fluorobutyrophenone(CAS DataBase Reference)
• NIST Chemistry Reference: 4-Chloro-4'-fluorobutyrophenone(3874-54-2)
• EPA Substance Registry System: 4-Chloro-4'-fluorobutyrophenone(3874-54-2)

Safety Data

• Hazard Codes: Xn,Xi
• Statements: 22-36/37/38-20/21/22
• Safety Statements: 24/25-36-26
• WGK Germany: 3
• TSCA: Yes
• Hazardous Substances Data: 3874-54-2(Hazardous Substances Data)

Usage

Uses

Used in Organic Synthesis:
4-Chloro-4'-fluorobutyrophenone is used as a synthetic intermediate for the preparation of a variety of organic compounds. Its presence of electron-withdrawing chlorine and fluorine atoms influences the reactivity of the molecule, making it a versatile building block in the synthesis of pharmaceuticals, agrochemicals, and other specialty chemicals.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, 4-Chloro-4'-fluorobutyrophenone is utilized as a key component in the development of new drugs. Its unique structure allows for the creation of novel molecular entities with potential therapeutic applications, contributing to the advancement of medicine and the treatment of various diseases.
Used in Agrochemical Industry:
4-Chloro-4'-fluorobutyrophenone also finds application in the agrochemical sector, where it is employed in the synthesis of new pesticides and other crop protection agents. Its chemical properties enable the design of innovative compounds that can effectively control pests and diseases, thereby enhancing crop yields and food security.
Used in Specialty Chemicals:
In the specialty chemicals market, 4-Chloro-4'-fluorobutyrophenone is used as a precursor for the production of various high-value chemicals. Its unique combination of functional groups allows for the creation of tailored compounds with specific properties, catering to the needs of diverse industries such as materials science, coatings, and fragrances.

Synthetic route

fluorobenzene (462-06-6) + 4-Chlorobutanoyl chloride (4635-59-0) → 4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2)

Conditions	Yield
With aluminum (III) chloride In dichloromethane at 20℃; for 4h; Time;	90%
With aluminium trichloride In carbon disulfide at 20℃; for 2h;	73.2%
With aluminium trichloride

4-chloro-1-(4-fluorophenyl)-1,1-(ethylenedioxy)butane (3308-94-9) → 4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2)

Conditions	Yield
In(OSO2CF3)3 In acetone at 100℃; for 0.0833333h; microwave irradiation;	89%

4-flourophenylmagnesium bromide (352-13-6) + 4-Chlorobutanoyl chloride (4635-59-0) → 4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2)

Conditions	Yield
Stage #1: 4-Chlorobutanoyl chloride With 1-methyl-pyrrolidin-2-one In toluene at 0℃; for 0.5h; Stage #2: 4-flourophenylmagnesium bromide In tetrahydrofuran; toluene at -10 - 0℃; for 4.25h; chemoselective reaction;	88%

1-(4-chlorobut-1-yn-1-yl)-4-fluorobenzene (1183278-95-6) → 4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2)

Conditions	Yield
With iron(III) chloride; water; silver(I) triflimide In 1,4-dioxane for 18h; regioselective reaction;	85%
With water; bis(trifluoromethanesulfonyl)amide In 1,4-dioxane at 100℃;	85%
With water In 1,4-dioxane at 80 - 120℃; regioselective reaction;	85%

1-(4-fluorophenyl)cyclobutan-1-ol (339365-53-6) → 4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2)

Conditions	Yield
With manganese(II) triflate; tetrabutylammonium acetate; acetic acid; magnesium chloride In acetonitrile at 25℃; for 3.5h; Inert atmosphere; Electrochemical reaction; Sealed tube;	84%
With 1,10-Phenanthroline; tert-butylhypochlorite; silver trifluoromethanesulfonate In acetonitrile at 20℃; for 6h; Inert atmosphere; Schlenk technique; regioselective reaction;	81%

4-chlorobutyraldehyde (6139-84-0) + 1-Bromo-4-fluorobenzene (460-00-4) → 4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2)

Conditions	Yield
With Quinuclidine; 4,4'-di-tert-butyl-2,2'-bipyridine nickel(II) bromide; [Ir(C6H2F2-C5H3NCF3)2(4,4′-di-tert-butyl-2,2′-dipyridyl)]; potassium carbonate In 1,4-dioxane at 20℃; for 20h; Inert atmosphere; Sealed tube; Irradiation;	77%
With palladium diacetate; 9,10-phenanthrenequinone; potassium hydrogencarbonate; 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene In acetone at 20℃; for 24h; Reagent/catalyst; Irradiation;	71%

1-iodo-3-chloro-propane (6940-76-7) + 4-fluoroboronic acid (1765-93-1) + molybdenum hexacarbonyl (13939-06-5, 199620-15-0) → 4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2)

Conditions	Yield
Stage #1: 1-iodo-3-chloro-propane; 4-fluoroboronic acid With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In water; benzene at 20℃; for 24h; Suzuki-Miyaura Coupling; Inert atmosphere; Irradiation; Stage #2: molybdenum hexacarbonyl With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 70℃; Suzuki-Miyaura Coupling; Inert atmosphere;	68%

1-ethynyl-4-fluorobenzene (766-98-3) + 3-chloropropionyl peroxide (19263-25-3) → 4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2)

Conditions	Yield
With iron(III) trifluoromethanesulfonate; trifluorormethanesulfonic acid In tetrahydrofuran at 70 - 80℃; for 12.25h; Inert atmosphere; Schlenk technique;	60%

3-chloro-4'-fluoropropiophenone (347-93-3) + diethyl 4-chloromethyl-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylate (3613-34-1) → 4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2)

Conditions	Yield
With manganese; di-tert-butyl peroxide; α,α,α-trifluorotoluene at 100℃; for 48h; Inert atmosphere;	51%

1-Bromo-4-fluorobenzene (460-00-4) → 4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: iodine; magnesium / tetrahydrofuran / Inert atmosphere; Reflux; Sealed tube 1.2: 0 - 20 °C / Inert atmosphere; Sealed tube 2.1: acetic acid; manganese(II) triflate; magnesium chloride; tetrabutylammonium acetate / acetonitrile / 3.5 h / 25 °C / Inert atmosphere; Electrochemical reaction; Sealed tube View Scheme

para-thiocresol (106-45-6) + 4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2) → 1-(4-fluorophenyl)-4-(p-tolylthio)butan-1-one (132427-90-8)

Conditions	Yield
	100%
With triethylamine In tetrahydrofuran for 16h; Ambient temperature;	99%

N-methoxylamine hydrochloride (593-56-6) + 4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2) → 4-chloro-1-(4-fluorophenyl)butan-1-one O-methyl oxime (1352950-38-9)

Conditions	Yield
With pyridine at 20℃;	100%

4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2) → cyclopropyl(4-fluorophenyl)methanone (772-31-6)

Conditions	Yield
With sodium hydroxide In water at 60℃; for 5h;	100%

toluene-3-thiol (108-40-7) + 4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2) → 1-(Fluorophenyl)-4-(3-methylphenylthio)-1-butanone

Conditions	Yield
With triethylamine In tetrahydrofuran	99%
With triethylamine In tetrahydrofuran	99%

toluene-3-thiol (108-40-7) + 4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2) → 1-(4-Fluorophenyl)-4-(3-methylphenylthio)-1-butanone

Conditions	Yield
With triethylamine In tetrahydrofuran	99%

ethylene glycol (107-21-1) + 4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2) → 4-chloro-1-(4-fluorophenyl)-1,1-(ethylenedioxy)butane (3308-94-9)

Conditions	Yield
With toluene-4-sulfonic acid In water; toluene for 16h; Inert atmosphere; Reflux;	98%
With toluene-4-sulfonic acid In benzene for 18h; Heating;	93%
With toluene-4-sulfonic acid In benzene for 15h; Heating;	90%

4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2) + 1-(2,5-dimethylphenyl)piperazine (1013-25-8) → 4-[4-(2,5-dimethylphenyl)piperazin-1-yl]-1-(4-fluorophenyl)butan-1-one

Conditions	Yield
With sodium hydrogencarbonate; sodium iodide In acetonitrile for 22h; Reflux;	96%

4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2) → (+/-)-4-chloro-1-(4-fluorophenyl)butan-1-ol (51787-87-2)

Conditions	Yield
With sodium tetrahydroborate In ethanol at 0℃; for 7h;	95%
With sodium tetrahydroborate In ethanol at 0 - 20℃; for 3h;	94%
With sodium tetrahydroborate In ethanol at 0 - 20℃; for 12h;	93%

4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2) → 1-iodo-3-(p-fluorophenylcarbonyl)propane (40862-32-6)

Conditions	Yield
With sodium iodide In butanone for 3h; Heating;	95%
With sodium iodide In acetone for 24h; Reflux;	92%
With sodium iodide In acetone for 16h; Reflux;	77%
In sodium iodide; butanone
With sodium iodide In [(2)H6]acetone for 8h; Reflux;

4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2) → 4-(n-butyl)fluorobenzene (20651-65-4)

Conditions	Yield
With nickel In tetrahydrofuran for 15h; Heating;	95%

4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2) → C10H10FN3O (154440-76-3)

Conditions	Yield
With sodium azide In N,N-dimethyl-formamide	95%
With sodium azide; potassium iodide In N,N-dimethyl-formamide at 90℃;

4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2) + (S)-2-methylpropane-2-sulfinamide (343338-28-3) → (S,E)-N-(4-chloro-1-(4-fluorophenyl)butylidene)-2-methylpropane-2-sulfinamide (1218989-31-1)

Conditions	Yield
With titanium (IV) ethoxide In tetrahydrofuran at 65℃; for 48h; Inert atmosphere;	94%

4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2) → C10H11FO

Conditions	Yield
Stage #1: 4-(4-fluorophenyl)-4-oxo-n-butyl chloride With C32H33FeN3O2Si; 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane In toluene at -40 - 20℃; for 2h; Schlenk technique; Glovebox; Stage #2: With potassium carbonate In methanol; toluene at 20℃; for 12h; Schlenk technique; Glovebox; enantioselective reaction;	94%

4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2) + 1-Phenyl-1,3,8-triaza-spiro[4.5]decan-4-one (1021-25-6) → spiperone (749-02-0)

Conditions	Yield
With diisopropylamine In N,N-dimethyl-formamide at 80℃; for 17h; Inert atmosphere;	93%
With triethylamine; potassium iodide In acetonitrile for 20h; Heating;	74%
With triethylamine; potassium iodide In acetonitrile for 20h; Inert atmosphere; Reflux;	63%

4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2) + potassium thioacetate (10387-40-3) → S-(4-(4-fluorophenyl)-4-oxobutyl) ethanethioate

Conditions	Yield
In N,N-dimethyl-formamide at 0 - 20℃; for 10h; Inert atmosphere;	92%

4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2) → (1R)-(+)-4-chloro-1-(4-fluorophenyl)butan-1-ol (126640-11-7)

Conditions	Yield
With B-chlorodiisopinocampheylborane In diethyl ether at -25℃; for 16h;	90%
With C22H27Cl2CoN3O; sodium triethylborohydride; 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane In tetrahydrofuran at 20℃; for 2h; Inert atmosphere; enantioselective reaction;	87%
Stage #1: 4-(4-fluorophenyl)-4-oxo-n-butyl chloride With Triethoxysilane; (S,E)-(+)-2,6-diisopropyl-N-(2-((2-(4-phenyl-4,5-dihydrooxazol-2-yl)phenyl)amino)benzylidene)aniline; sodium triethylborohydride; cobalt(II) chloride In tetrahydrofuran; dichloromethane at 20℃; for 15h; Schlenk technique; Inert atmosphere; Stage #2: With potassium carbonate In tetrahydrofuran; methanol; dichloromethane at 20℃; for 2h; Schlenk technique; Inert atmosphere; enantioselective reaction;	75%
Multi-step reaction with 2 steps 1: 81 percent / NaBH4 / methanol / 4 °C View Scheme
With B-chlorodiisopinocampheylborane In tetrahydrofuran; diethyl ether; 2,2'-iminobis[ethanol] at 25℃;

4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2) → (1S)-(-)-4-chloro-1-(4-fluorophenyl)butan-1-ol (126640-10-6)

Conditions	Yield
With (-)-diisopinocamphenylborane chloride In diethyl ether at -25℃; for 16h;	90%
Multi-step reaction with 2 steps 1: 81 percent / NaBH4 / methanol / 4 °C View Scheme
With (-)-diisopinocamphenylborane chloride In tetrahydrofuran; diethyl ether; 2,2'-iminobis[ethanol] at 25℃;

4-fluorobenzylic alcohol (459-56-3) + 4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2) → cyclopropyl-[4-(4-fluoro-benzyloxy)-phenyl]-methanone (868699-44-9)

Conditions	Yield
With tetrabutylammomium bromide; sodium hydride In tetrahydrofuran at 30℃; for 18h;	90%

4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2) → (-)-4-chloro-1-(4-fluorophenyl)butan-1-ol

Conditions	Yield
Stage #1: 4-(4-fluorophenyl)-4-oxo-n-butyl chloride With (S)-2,2',6,6'-tetramethoxy-4,4'-bis(diphenylphosphino)-3,3'-bipyridine; phenylsilane; copper(II) acetate monohydrate In toluene at -20 - 20℃; for 48h; Stage #2: With hydrogenchloride In water; toluene Reagent/catalyst; enantioselective reaction;	90%

fluoroiodomethane (373-53-5) + 4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2) → 5-chloro-1-fluoro-2-(4-fluorophenyl)pentan-2-ol

Conditions	Yield
With methyllithium lithium bromide In tetrahydrofuran; diethyl ether at -78℃; for 0.0833333h; Inert atmosphere;	90%

1-phenylmethylpiperazine (2759-28-6) + 4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2) → cyclopropyl-{4-(4-benzylpiperazin-1-yl)phenyl}methanone

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 140℃;	90%

4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2) → 1-(4-chlorobutyl)-4-fluorobenzene (54540-58-8)

Conditions	Yield
With triethylsilane; trifluoroacetic acid at 0℃; for 2h;	89%
With hydrogen; palladium on activated charcoal In ethanol
With hydrogenchloride; mercury dichloride; zinc In toluene for 5h; Reflux;
With triethylsilane In trifluoroacetic acid

4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2) + 4-flourophenylmagnesium bromide (352-13-6) → δ-Hydroxy-δ-bis(p-fluorophenyl)butyl chloride (51787-80-5)

Conditions	Yield
In diethyl ether Heating;	88.4%

4-hydroxy-4-phenylpiperidin (40807-61-2) + 4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2) → 1-(4-fluorophenyl)-4-(4-hydroxy-4-phenylpiperidin-1-yl)butan-1-one (3109-12-4)

Conditions	Yield
With sodium hydrogencarbonate; potassium iodide In toluene for 24h; Reflux;	88%
With potassium iodate; potassium carbonate In toluene Inert atmosphere;	27%
With toluene; potassium iodide

4-(4-chlorophenyl)-4-hydroxypiperidine (39512-49-7) + 4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2) → haloperidol (52-86-8)

Conditions	Yield
With potassium carbonate; potassium iodide In acetonitrile at 75℃; for 24h; Temperature;	88%
With potassium iodide In toluene for 45h; Reflux;	85%
With potassium iodide In toluene at 130℃; for 45h; Sealed tube;	79%

1-(4-chlorophenyl)-1,4-diazepane (41885-98-7) + 4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2) → 4-(4-(4-chlorophenyl)-1,4-diazepan-1-yl)-1-(4-fluorophenyl)butan-1-one

Conditions	Yield
With potassium carbonate; potassium iodide In 1,2-dimethoxyethane for 18h; Heating;	87%

[bis(acetoxy)iodo]benzene (3240-34-4) + 4-(4-fluorophenyl)-4-oxo-n-butyl chloride (3874-54-2) → C12H12ClFO3 (1394244-16-6)

Conditions	Yield
With tetrabutylammomium bromide; potassium hydroxide In 1,4-dioxane at 20℃; for 1h;	87%

Upstream product

• 3308-94-9 4-chloro-1-(4-fluorophenyl)-1,1-(ethylenedioxy)butane 
• 6940-76-7 1-iodo-3-chloro-propane 
• 1765-93-1 4-fluoroboronic acid 
• 13939-06-5 molybdenum hexacarbonyl 
• 347-93-3 3-chloro-4'-fluoropropiophenone 
• 3613-34-1 diethyl 4-chloromethyl-1,4-dihydro-2,6-dimethylpyridine-3,5-dicarboxylate 
• 460-00-4 1-Bromo-4-fluorobenzene 
• 6139-84-0 4-chlorobutyraldehyde 
• 766-98-3 1-ethynyl-4-fluorobenzene 
• 19263-25-3 3-chloropropionyl peroxide 
• 339365-53-6 1-(4-fluorophenyl)cyclobutan-1-ol 
• 1183278-95-6 1-(4-chlorobut-1-yn-1-yl)-4-fluorobenzene 
• 352-13-6 4-flourophenylmagnesium bromide 
• 4635-59-0 4-Chlorobutanoyl chloride 

Downstream Products

• 3109-12-4 4-(4-hydroxy-4-phenyl-1-piperidinyl)-1-(4-fluorophenyl)-1-butanone 
• 71526-80-2 7a-(4-fluoro-phenyl)-hexahydro-pyrrolo[2,1-b]oxazole 
• 21492-58-0 4-(2,3-dihydro-5H-benzo[f][1,4]oxazepin-4-yl)-1-(4-fluoro-phenyl)-butan-1-one 
• 54981-16-7 9-[4-(4-fluoro-phenyl)-4-oxo-butyl]-5-methyl-1-oxa-3,9-diaza-spiro[5.5]undecan-2-one 
• 26728-12-1 8-[4-(4-fluoro-phenyl)-4-oxo-butyl]-3-phenyl-1-oxa-3,8-diaza-spiro[4.5]decane-2,4-dione 
• 1239-40-3 2-[4-(4-fluoro-phenyl)-4-oxo-butyl]-1,1-dioxo-1,2-dihydro-1λ⁶-benzo[d]isothiazol-3-one 
• 56657-97-7 1-(4-fluoro-phenyl)-4-(3H-spiro[isobenzofuran-1,4'-piperidin]-1'-yl)-butan-1-one 
• 51582-69-5 1-(4-fluoro-phenyl)-4-[4-(2-trifluoromethyl-thioxanthen-9-ylidene)-piperidin-1-yl]-butan-1-one 
• 1238-79-5 4-(7,9-dimethyl-8-oxa-2-aza-spiro[4.5]dec-2-yl)-1-(4-fluoro-phenyl)-butan-1-one 
• 3311-94-2 4,4-bis(4-fluorophenyl)-3-butenyl chloride 
• 51787-81-6 1,4-Bis(4-fluorophenyl)butanol 

Relevant articles and documents

Preparation method of flupiperidinol

The invention belongs to the technical field of medicine preparation, and particularly relates to a preparation method of flupiperidinol. The preparation method of the fluoropiperidinol, provided by the invention, comprises the following steps of providing 4-(4-chlorphenyl)-4-piperidinol of which the purity is 99% or above, providing 4-chloro-1-(4-fluorophenyl)butan-1-one of which the purity is more than 99%, mixing the 4-(4-chlorphenyl)-4-piperidinol, 4-chloro-1-(4-fluorophenyl)butan-1-one, an alkaline substance and a catalyst, and carrying out a first substitution reaction to obtain a crudeproduct, and mixing the crude product with an organic solvent, and sequentially carrying out reflux and crystallization to obtain the flupiperidinol. The flupiperidinol prepared according to the preparation method provided by the invention has relatively high yield and purity.

Direct C-H Arylation of Aldehydes by Merging Photocatalyzed Hydrogen Atom Transfer with Palladium Catalysis

Herein, we report that merging palladium catalysis with hydrogen atom transfer (HAT) photocatalysis enabled direct arylations and alkenylations of aldehyde C-H bonds, facilitating visible light-catalyzed construction of a variety of ketones. Tetrabutylammonium decatungstate and anthraquinone were found to act as synergistic HAT photocatalysts. Density functional theory calculations suggested a Pd0-PdII-PdIII-PdI-Pd0 pathway and revealed that regeneration of the Pd0 catalyst and the photocatalyst occurs simultaneously in the presence of KHCO3. This regeneration features a low energy barrier, promoting efficient coupling of the palladium catalytic cycle with the photocatalytic cycle. The work reported herein suggests great promise for further applications of HAT photocatalysis in palladium-catalyzed cross-coupling and C-H functionalization reactions to be successful.

Mn-Enabled Radical-Based Alkyl-Alkyl Cross-Coupling Reaction from 4-Alkyl-1,4-dihydropyridines

Highly efficient alkylation of β-chloro ketones and their derivatives was achieved by means of domino dehydrochlorination/Mn-enabled radical-based alkyl-alkyl cross-coupling reaction. In situ-generated α,β-unsaturated ketones and their analogues were identified as the reaction intermediates. Known bioactive compounds, such as melperone and azaperone, could be easily prepared from β-chloropropiophenone in two steps.

Manganese-Catalyzed Electrochemical Deconstructive Chlorination of Cycloalkanols via Alkoxy Radicals

A manganese-catalyzed electrochemical deconstructive chlorination of cycloalkanols has been developed. This electrochemical method provides access to alkoxy radicals from alcohols and exhibits a broad substrate scope, with various cyclopropanols and cyclobutanols converted into synthetically useful β- and γ-chlorinated ketones (40 examples). Furthermore, the combination of recirculating flow electrochemistry and continuous inline purification was employed to access products on a gram scale.

Palladium and visible-light mediated carbonylative Suzuki-Miyaura coupling of unactivated alkyl halides and aryl boronic acids

Herein, a simple and efficient method for the palladium-catalyzed carbonylation of aryl boronic acids with unactivated alkyl iodides and bromides under visible-light irradiation, ambient temperature and low CO-pressure is presented. Notably, the procedure uses readily available equipment and an inexpensive palladium catalyst to generate the key alkyl radical intermediate. These mild conditions enabled the synthesis of a range of functionalized aryl alkyl ketones including the antipsychotic drug, melperone.

Direct Aldehyde C-H Arylation and Alkylation via the Combination of Nickel, Hydrogen Atom Transfer, and Photoredox Catalysis

A mechanism that enables direct aldehyde C-H functionalization has been achieved via the synergistic merger of photoredox, nickel, and hydrogen atom transfer catalysis. This mild, operationally simple protocol transforms a wide variety of commercially available aldehydes, along with aryl or alkyl bromides, into the corresponding ketones in excellent yield. This C-H abstraction coupling technology has been successfully applied to the expedient synthesis of the medicinal agent haloperidol.

Iron-Catalyzed Radical Decarboxylative Oxyalkylation of Terminal Alkynes with Alkyl Peroxides

An iron-catalyzed oxyalkylation of alkynes with alkyl peroxides as the alkylating reagents has been investigated. Alkyl peroxides are readily available from aliphatic acids and serve simultaneously as the alkylating reagents and internal oxidants. Primary, secondary, and tertiary alkyl groups of aliphatic acids were readily incorporated into C?C triple bonds and diverse α-alkylated ketones were synthesized. Mechanism studies revealed that this reaction involves highly reactive alkyl free radicals. A unique equilibrium between lauric acid and water catalyzed by the iron(III) catalyst was observed.

Regioselective Synthesis of Carbonyl-Containing Alkyl Chlorides via Silver-Catalyzed Ring-Opening Chlorination of Cycloalkanols

A novel and regioselective approach to carbonyl-containing alkyl chlorides via silver-catalyzed ring-opening chlorination of cycloalkanols is reported. Concurrent C(sp3)-C(sp3) bond cleavage and C(sp3)-Cl bond formation efficiently occur with good yields under mild conditions, and the chlorinated products are readily transformed into other useful synthetic intermediates and drugs. The reaction features complete regioselectivity, high efficiency, and excellent practicality. (Chemical Equation Presented).

Bimetallic nanosized solids with acid and redox properties for catalytic activation of C-C and C-H bonds

A new approach is presented to form self-supported bimetallic nanosized solids with acid and redox catalytic properties. They are water-, air- and H2-stable, and are able to activate demanding C-C and C-H reactions. A detailed mechanistic study on the formation of the Ag-Fe bimetallic system shows that a rapid redox-coupled sequence between Ag+, O2 (air) and Fe2+ occurs, giving monodisperse Ag nanoparticles supported by O-bridged diatomic Fe3+ triflimides. The system can be expanded to Ag nanoparticles embedded within a matrix of Cu2+, Bi3+ and Yb3+ triflimide.

A combined computational and experimental investigation of the oxidative ring-opening of cyclic ethers by oxoammonium cations

The propensity of oxoammonium cations to facilitate the oxidative ring-opening of cyclic ethers to their corresponding distal hydroxy ketones is investigated. The reaction has been evaluated using experimental and computational methods to gain deeper insight into trends in reactivity.