Access to Aryl and Heteroaryl Trifluoromethyl Ketones from Aryl Bromides and Fluorosulfates with Stoichiometric CO

Abstract

We report a sequential one-pot preparation of aromatic trifluoromethyl ketones starting from readily accessible aryl bromides and fluorosulfates, the latter easily prepared from the corresponding phenols. The methodology utilizes low pressure carbon monoxide generated ex situ from COgen to generate Weinreb amides as reactive intermediates that undergo monotrifluoromethylation affording the corresponding aromatic trifluoromethyl ketones (TFMKs) in good yields. The stoichiometric use of CO enables the possibility for accessing 13 C-isotopically labeled TFMK by switching to the use of 13 COgen.

A Broad-Spectrum, Catalytic Amidation of Sulfonyl Fluorides and Fluorosulfates

“…Flash column chromatography was performed on 200-300 mesh silica gel (Huanghai, China). 2-(diphenylphosphanyl)-5-methylbenzenesulfonyl fluoride (1a), [1] 4-methylbenzenesulfonyl fluoride (1c), [2] 4-methoxybenzenesulfonyl fluoride (1e), [2] 2-methylbenzenesulfonyl fluoride (1f), [3] 4-(trifluoromethyl)benzenesulfonyl fluoride (1g), [3] 4-fluorobenzenesulfonyl fluoride (1h), [4] benzenesulfonyl fluoride (1i), [4] 4-(tert-butyl)benzenesulfonyl fluoride (1l), [2] naphthalene-1-sulfonyl fluoride (1m), [2] ((1S,4R)-7,7-dimethyl-2-oxobicyclo[2.2.1]heptan-1-yl)methanesulfonyl fluoride (1n), [2] 4-methoxyphenyl fluorosulfate (4b), [5] 4-isopropylphenyl fluorosulfate (4d), [6] 4-iodophenyl fluorosulfate (4e), [7] 3,5-dimethylphenyl fluorosulfate (4f), [8] benzo [d] [1,3]dioxol-5-yl fluorosulfate (4g), [3] phenyl fluorosulfate (4h), [5] phenyl fluorosulfate, [3] 4-bromophenyl fluorosulfate (4i), [9] [1,1'biphenyl]-4-yl fluorosulfate (4j), [3] (8R,9S,13S,14S)-13-methyl-17-oxo- 7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-yl fluorosulfate (4n), [10] (8R,9S,13S,14S,17R)-17-ethynyl-17-hydroxy-13-methyl- 7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-yl fluorosulfate (4o), [3] 3-nitrobenzenesulfonyl fluoride (8), [3] 4-(2-(pyrrolidin-1-yl)ethoxy)aniline (12), [11] 1H-benzo [d] [1,2,3]triazol-1-yl benzenesulfonate (16),…”

“…Compound 5o was prepared according to a modification of the general procedure ( N-((3s,5s,7s)-adamantan-1-yl)benzenesulfonamide (15) Figure S1. Image A: the multidecagram-scale reaction equipped with a condensor, a pressureequalizing dropping funnel, a bubbler and a 1-L buffer bottle; Image B: the product 15 during purification; Image C: the product 15 after purification.…”

Synthetic Approaches to N‐Methoxy‐N‐methylamides

“…Synthetic Approaches to N-Methoxy-N-methylamides BULLETIN OF THE KOREAN CHEMICAL SOCIETY to give the corresponding trifluoromethyl ketones (Scheme 41). 74 The Pd-catalyzed aminocarbonylation of aryl nonaflates (75) and (CH 3 O)NHCH 3 ÁHCl using Mo(CO) 6 was very useful for the preparation of Weinreb amides. The reaction of aryl nonaflates and (CH 3 O)NHCH 3 ÁHCl using 2 mol% Pd(OAc) 2 , Mo(CO) 6 , and Xantphos ligand in the presence of 3 equiv of DBU in dioxane at 120 C under microwave irradiation gave the corresponding N-methoxy-Nmethylamides (Scheme 42).…”

“…These intermediates were then treated with 2 equiv of trimethyl(trifluoromethyl)silane (TMSCF 3 ) and tetramethylammonium fluoride (TMAF) as an activator, followed by tetrabutylammonium fluoride (TBAF) workup, to give the corresponding trifluoromethyl ketones (Scheme 41). 74 …”

Nickel-Catalyzed Photodehalogenation of Aryl Bromides

“…1 These processes are of significant industrial relevance, as polyhalogenated entities such as polybrominated diphenyl ethers (PBDE) are known persistent organic pollutants, flame retardants and health hazards that have been banned by the Stockholm convention. 2 Therefore, the synthetic community has been challenged to design efficient, reliable and practical catalytic dehalogenation techniques. Whilst radical pathways based on the utilization of tin hydride or metalhalogen exchange techniques with stoichiometric amounts of metal complexes have become routine in the dehalogenation arena (Scheme 1, top left), 3 the formation of toxic byproducts, the need for stoichiometric reductants and/or the poor functional group compatibility reinforce a change in strategy.…”