Directed ortho-Metalation of Arenesulfonyl Fluorides and Aryl Fluorosulfates

Abstract

Studies on directed ortho-metalation (DoM) of arenesulfonyl fluorides (ArSO2F) with in situ electrophile trapping are presented. Under optimized conditions (LDA, THF, –78 °C), a series of model substrates was mono- and difunctionalized with trimethylsilyl chloride in good yields. The synthetic results reveal powerful directing character of the SO2F group, being ahead of bromine and methoxy substituents. Under the same metalation conditions, aryl fluorosulfates (ArOSO2F) display fragmentation to arynes and migration of the SO2F group to the ortho position (anionic thia-Fries rearrangement).

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-7,8,9,11,12,13,14,15,16,17decahydro-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), [12] were prepared according to literature procedures. NMR data were in agreement with the literature data.…”

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),…”

“…0.15 mL of this mixture was removed and diluted with CDCl3 (0.50 mL). The diluted mixture was transferred to an NMR tube and analyzed by 1 H NMR spectroscopy.A mixture of 1H-benzo[d][1,2,3]triazol-1-yl benzenesulfonate 16 (27.5 mg, 0.10 mmol), 1-amantadine 2d (15.1 mg, 1.0 equiv), 1,1,3,3-tetramethyldisiloxane (36 μL, 2.0 equiv), and DIPEA (35μL, 2.0 equiv) in NMP (0.50 mL) was stirred at 25 C in an aluminum heating block for 120 min. Then the mixture was diluted with CDCl3 (1.00 mL).…”

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

“…The latter result was particularly interesting, as TMP-benzamides are attractive substrates for dearomatization reactions, while their preparation from amine, NaH and aroyl chlorides in refluxing toluene for 24 h is only poorly efficient (12-34%). [30][31][32] Importantly, under our 'metalation' conditions benzoyl fluoride reacted much better than other halides, 33 and presence of TMSCl (applied originally for in situ trapping of ortho-lithiated species) 29 appeared to be beneficial for the synthesis of carboxamides. 34 Although preparation of amides by acyl substitution with lithium amide bases in esters and activated amides was thoroughly explored by Szostak, 35,36 the methodology was not demonstrated for preparation of sterically hindered N,N-disubstituted systems.…”

“…Scheme 3 Directed ortho-metalation of benzenesulfonyl fluoride reported in the literature29 (top), and preliminary reactions of benzoyl halides with lithium…”