Copper-Catalyzed Hydrogen/Iodine Exchange in Terminal and 1‑Iodoalkynes

Detailed kinetic profiles of the copper-catalyzed exchange between the acetylenic proton and iodide of terminal and 1-iodophenylacetylenes are reported. The electronic nature of the alkynes does not influence the equilibrium of the exchange (<i>K</i>_eq = 1), only the rate of equilibration. Notably, the profiles are the same for electron-rich, methyl-substituted phenylacetylenes but are divergent for electron-deficient, trifluoromethyl-substituted variants. The heretofore unreported exchange process yields practical considerations regarding reactions involving iodo and terminal alkynes

Synthesis of β‑Ketosulfonamides Derived from Amino Acids and Their Conversion to β‑Keto-α,α-difluorosulfonamides via Electrophilic Fluorination

β-Ketosulfonamides derived from Boc or Cbz-protected amino acids bearing hydrophobic side chains were prepared in good to excellent yield by treating <i>N</i>-allyl, <i>N</i>-alkyl methanesulfonamides with <i>n</i>-BuLi, followed by reaction of the resulting carbanion with methyl esters of <i>N</i>-protected l-amino acids. The analogous reaction using the dianion derived from an <i>N</i>-alkyl methanesulfonamide proceeded in much lower yield. Electrophilic fluorination of the β-ketosulfonamides using Selectfluor in the presence of CsF in DMF at room temperature for 15–60 min provided β-keto-α,α-difluorosulfonamides in good to excellent yields. The allyl protecting group could be removed in good yield using cat. Pd­(PPh)₃)₄ and dimethyl barbituric acid. When the fluorination reaction was performed with Cs₂CO₃ as base, β-ketosulfonamides derived from Val, Leu or Ile gave the expected β-keto-α,α-difluorosulfonamides, while β-ketosulfonamides derived from Ala, Phe, or hPhe gave the hydrates of the imino β-keto-α,α-difluorosulfonamides

Synthesis of β‑Ketosulfonamides Derived from Amino Acids and Their Conversion to β‑Keto-α,α-difluorosulfonamides via Electrophilic Fluorination

β-Ketosulfonamides derived from Boc or Cbz-protected amino acids bearing hydrophobic side chains were prepared in good to excellent yield by treating <i>N</i>-allyl, <i>N</i>-alkyl methanesulfonamides with <i>n</i>-BuLi, followed by reaction of the resulting carbanion with methyl esters of <i>N</i>-protected l-amino acids. The analogous reaction using the dianion derived from an <i>N</i>-alkyl methanesulfonamide proceeded in much lower yield. Electrophilic fluorination of the β-ketosulfonamides using Selectfluor in the presence of CsF in DMF at room temperature for 15–60 min provided β-keto-α,α-difluorosulfonamides in good to excellent yields. The allyl protecting group could be removed in good yield using cat. Pd­(PPh)₃)₄ and dimethyl barbituric acid. When the fluorination reaction was performed with Cs₂CO₃ as base, β-ketosulfonamides derived from Val, Leu or Ile gave the expected β-keto-α,α-difluorosulfonamides, while β-ketosulfonamides derived from Ala, Phe, or hPhe gave the hydrates of the imino β-keto-α,α-difluorosulfonamides

Tandem Reaction Progress Analysis as a Means for Dissecting Catalytic Reactions: Application to the Aza-Piancatelli Rearrangement

Continuing developments in the elucidation techniques of complex catalytic processes is of foremost importance to modern synthetic chemistry, and the identification of efficient synthetic techniques relies on precise, reliable, and adaptable methods to dissect the mechanism of a given transformation. Currently, methods of reaction development are grounded upon the systematic modification of specific variablessuch as temperature, time, concentration, etc.to account for and control the dynamic series of coupled equilibria within a catalytic environment. On the other hand, tandem reaction analytical methods that involve the concomitant use of different instruments to probe a reaction can provide time-resolved information regarding active chemical species and facilitate the interrogation and optimization of the system. Herein, we report our study applying tandem in situ ReactIR and HPLC-MS monitoring to the dysprosium­(III) triflate-catalyzed aza-Piancatelli rearrangement of 2-furylcarbinols, a reaction that grants access to <i>trans</i>-4,5-disubstituted cyclopentenonescommon motifs in important biologically relevant and natural compounds. With a prototype automated sampling apparatus, information was obtained about the intrinsic chemoselectivity of the reaction, and previously unseen intermediates were observed, allowing for a more detailed reaction mechanism to be substantiated. The advantages of applying this type of tandem measurement to study these types of systems are also discussed