One-pot near-ambient temperature syntheses of aryl(difluoroenol) derivatives from trifluoroethanol

Suzuki–Miyaura Coupling Reactions of Iodo(difluoroenol) Derivatives, Fluorinated Building Blocks Accessible at Near-Ambient Temperatures

“…However, it was necessary to keep the reaction time as short as possible as HF addition product 14 was produced (due to the strong electron-withdrawing effect of the nitro group). This HF addition product was previously observed during our Negishi coupling work and arises from LiF formed during the generation of difluorovinylzinc reagent 7 . Fluoride is also formed from the trifluoroborate salts (vide infra), and HF addition may therefore be a consequence of their use.…”

“…25%). Addition of DMPU cosolvent was necessary for a respectable yield of 8a ; the urea cosolvent ensures full conversion of 1b to the organozinc intermediate . Both iodides were found to be stable after purification and could be stored under N 2 in the refrigerator without decomposition (3 months).…”

“…To improve borate solubility, more polar solvents were investigated; alcohols were chosen as relatively sustainable candidates . The 3-nitrophenyl borate 9n was chosen to optimize the reaction conditions as products 10an and 10bn are difficult compounds to generate in good yield (as we and others , have found in previous work). Borate 9n , iodide 8b , Cs 2 CO 3 (3 equiv), and (Ph 3 P) 2 PdCl 2 (2 mol %) dissolved fully in an alcohol ( n- PrOH, i- PrOH, or t -BuOH)/water (2.7:1) mixture at 90 °C.…”

“…Trifluoroborate 6 was prepared and used in Suzuki–Miyaura couplings; although a low-temperature procedure was still required to prepare 6 , the avoidance of tin reagents was a significant development. We have recently developed a sequence in which dehydrofluorination/metalation chemistry of 1b and 1c can be carried out at close to ambient temperature and followed by a Negishi coupling reaction (Scheme ). − We were able to use the intermediate organozinc reagents in Negishi coupling reactions to prepare a range of difluorinated alkene products, in high yields in some cases.…”

Modular Construction of Fluoroarenes from a New Difluorinated Building Block by Cross‐Coupling/Electrocyclisation/Dehydrofluorination Reactions

“…For simple arenes, these novel methods are hard to beat;h owever,n ot all precursor types are readily available.Astrategically different approach to fluoroarene synthesis could start from nonfluorinated species like indanones by carbene transfer and rearrangement, [11] or from readily available fluorinated building blocks like fluoroenynes, [12] fluorinated dienophiles [13] or most recently, and very effectively,f rom difluoroalkenes [14] by electrophilic cyclisation or Ni-catalysed [2+ +2+ +2]-cycloaddition. Acetal 1 and carbamate 2 (Figure 1), which are readily-prepared from trifluoroethanol, [15] can be converted to organozinc halides 3 and 4,w hich can be deployed in Negishi coupling reactions [16] with aryl halides. Iodides 5 and 6 underwent Suzuki-Miyaura couplings with aw ide range of Molander borates, [17] while Katz and co-workers [18] have shownh ow acetal 1 can be converted to Molander borate 7.…”