Merging hypervalent iodine and sulfoximine chemistry: a new electrophilic trifluoromethylation reagent

Abstract

Two prominent trifluoromethylation reagent classes join forces in a bench stable hypervalent iodosulfoximine CF3 transfer agent. We report its synthesis, properties and reactivity, opening up new possibilities in trifluoromethylation chemistry.

Direct Trifluoromethylation of Alcohols Using a Hypervalent Iodosulfoximine Reagent

“…Taking heptane-Scheme2.Substrate scope of trifluoromethylation of aliphaticalcohols with 2.F or all substrates which are oils no heating was required, in cases where the starting material was as olid the reaction was conducted at the melting pointoft he compound if applicable or in solvent. Yields were based on reagent 2 and determined by 19 1,6-diol, we found the reagent to have 56:40 chemoselectivity for primary alcohols vs. secondary,f urther highlighting the good reactivity of 2 with secondary alcohols. The chemoselectivity for primary alcohols over tertiary gave 73:27 selectivity when using 3-(hydroxymethyl)-1-adamantol.…”

“…Based on our previousf indings, [17] we expected the reagents to form a2 :1 reagent•Zna dduct, DFT calculations on the optimized adducts indicated that [ZnNTf 2 (2) 2 ]NTf 2 is thermodynamically favored compared to [ZnNTf 2 (1) 2 ]NTf 2 by 6kcal mol À1 in solution (see Supporting Information for details). To furtherv alidate the predicted stoichiometry, 19 FNMR experiments werec onducted, which showed ad ownfield shift of the I-CF 3 signal upon addition of increasing amounts of Zn(NTf 2 ) 2 as ar esult of the increasingi odonium character of 2. [23] Broadened signals were observedu pon addition of up to 0.50 equiv.o ft he zinc catalyst, with sharpeneds ignals observed thereafter suggesting the likelihood of a2:1 adduct.…”

“…Scheme2.Substrate scope of trifluoromethylation of aliphaticalcohols with 2.F or all substrates which are oils no heating was required, in cases where the starting material was as olid the reaction was conducted at the melting pointoft he compound if applicable or in solvent. Yields were based on reagent 2 and determined by19 FNMR analysis. Yields of isolatedproducts are giveninparenthesis.…”

“…Figure1. Selectivity of reagent 2 for primary,secondary, and tertiaryalcohols..Y ields were based on reagent 2 and determined by19 FNMR spectroscopy.…”

Heterocyclic Hypervalent Iodine(III) Compounds with Fused Benziodazole and Tetrazole Rings (I-Substituted Tetrazolo[1,5-b][1,2]Benziodazoles)

“…69 However, it is comparable and only marginally shorter than the exocyclic HV I-O bond in the a related heterocylic compound with a hydroxy ligand, I-hydroxybenziodoxolone (2.00 Å), 70 and in the even more closely related benziodazole with methoxy ligands (2.23 Å). 54 More noteworthy is the length of the endocyclic I-N bond (2.37 Å), which was markedly longer than the I-N bonds in a bicyclic benziodazole with two HV I-N bonds (2.18 Å each), 71 I-chlorobenziodoazole (2.11 Å), 72 I-chlorosulfoximine (2.10 Å), I-trifluoromethylsulfoximine (2.28 Å), 73 and I-acetoxybenziodoazole (2.10 Å). 53 At the same time, the I-N bond in BIAT-OH 5 is shorter than I-N bonds with pronounced ionic character, e.g., in I-phenylbenziodazole (2.45), 74 and other compounds with pyridine coordinated to the HV iodine(III) atom (2.41-2.44 Å).…”