- Difluorocarbene transfer from a cobalt complex to an electron-deficient alkene
-
We report the synthesis of the trifluoromethyl cobalt(iii)tetraphenylporphyrinato complex [Co(TPP)CF3], which loses fluoride upon one-electron reduction and transfers a difluorocarbene moiety to n-butyl acrylate to produce the corresponding gem-difluorocyclopropane. Catalytic CF2 transfer from Me3SiCF3 to n-butyl acrylate becomes possible when directly using the divalent cobalt(ii) porphyrin catalysts in the presence of NaI.
- Goswami, Monalisa,De Bruin, Bas,Dzik, Wojciech I.
-
-
Read Online
- PREPARATION OF A PYRIMIDINYL-3,8-DIAZABICYCLO[3.2.1]OCTANYLMETHANONE DERIVATIVE AND SALT THEREOF
-
Methods for preparing ((S)-2,2-difluorocyclopropyl)-((1R,5S)-3-(2-((1-methyl-1H-pyrazol-4-yl)amino)pyrimidin-4-yl)-3,8-diazabicyclo[3.2.1]-octan-8-yl)methanone and intermediates used in the processes of preparation thereof.
- -
-
Page/Page column 23
(2022/01/12)
-
- Large-Scale Cyclopropanation of Butyl Acrylate with Difluorocarbene and Classical Resolution of a Key Fluorinated Building Block
-
To address challenges in the preparation of a key building block containing a difluorocyclopropane moiety, we have developed a new protocol for difluorocarbene generation that relies on a Krapcho-type dealkylation of ethyl bromodifluoroacetate (EBDFA), an inexpensive and readily available fluorinated feedstock. Application of DoE and kinetic modeling was used to understand key reaction parameters and identify an optimal process. We report two variants of this procedure that offer different processing advantages and that have both been scaled successfully multiple times to deliver hundreds of kilograms of the resulting difluorocyclopropane. To access a single enantiomer of the target compound, we have also developed a classical resolution strategy and recycling protocol for the undesired enantiomer to replace previous chromatographic methods for separation.
- Becirovic, Husein,Blasberg, Florian,Chen, Bo,Clarke, Hugh J.,Colombo, Matteo,Daddario, Pedro,Damon, David B.,Depretz, Christelle,Dumond, Yves R.,Goetz, Adam E.,Grilli, Maria D.,Han, Lu,Houck, Tim L.,Johnson, Amber M.,Jones, Kris N.,Jung, J?rg,Leeman, Michel,Liu, Fangfang,Lu, Cuong V.,Mangual, Emilio J.,Nelson, Jade D.,Puchlopek-Dermenci, Angela L. A.,Ruggeri, Sally Gut,Simonds, Paul A.,Sitter, Barbara,Virtue, Daniel E.,Wang, Shuguang,Yu, Lixin,Yu, Tao
-
-
- Transition Metal-free gem-difluorocyclopropanation of Alkenes with CF3SiMe3?NaI System: a Recipe for Electron-deficient Substrates
-
Reaction of various electron-deficient alkenes, as well as functionalized styrene derivatives with CF3SiMe3?NaI system is studied. Relative reactivity of the substrates is established. It is shown that many α,β-unsaturated esters can
- Nosik, Pavel S.,Ryabukhin, Sergey V.,Grygorenko, Oleksandr O.,Volochnyuk, Dmitriy M.
-
p. 4104 - 4114
(2018/10/02)
-
- PYRIMIDINE AND TRIAZINE DERIVATIVES AND THEIR USE AS AXL INHIBITORS
-
Compounds of the general formula(I): (I) processes for the preparation of these compounds, compositions containing these compounds, and the uses of these compounds.
- -
-
Page/Page column 96
(2016/07/05)
-
- Methyl 2,2-difluoro-2-(fluorosulfonyl)acetate, a difluorocarbene reagent with reactivity comparable to that of trimethylsilyl 2,2-difluoro-2- (fluorosulfonyl)acetate (TFDA)
-
Under specific high concentration, high temperature conditions, methyl 2,2-difluoro-2-(fluorosulfonyl)acetate (MDFA) has been found to act as a very efficient source of difluorocarbene, exhibiting carbene reactivity characteristics comparable to those exhibited by trimethylsilyl 2,2-difluoro-2-(fluorosulfonyl)acetate (TFDA). For example, in reaction with highly unreactive n-butyl acrylate and using only 2 equiv of MDFA, a yield of 76% of difluorocyclopropane product was obtained after 2 days.
- Eusterwiemann, Steffen,Martinez, Henry,Dolbier, William R.
-
experimental part
p. 5461 - 5464
(2012/08/07)
-
- Competitive kinetic processes in the thermal rearrangement of 1,1-difluoro-2-(dideuteriomethylene)-cyclopropane
-
The synthesis of 1,1-difluoro-2-(dideuteriomethylene)-cyclopropane is reported along with the kinetics of its competing, reversible, first order rearrangements: (a) the degenerate rearrangement to 1,1-difluoro-3,3-dideuterio- 2-methylene-cyclopropane, and
- Dolbier Jr., William R.,Gautriaud, Emilie,Cai, Xiaohong
-
p. 339 - 343
(2007/10/03)
-
- Trimethylsilyl fluorosulfonyldifluoroacetate (TFDA): A new, highly efficient difluorocarbene reagent
-
TFDA is readily prepared from the reaction of fluorosulfonyldifluoroacetic acid with trimethylsilyl chloride, and it is a very effective and efficient source of difluorocarbene for use in addition reactions to alkenes of a broad scope of reactivities. Acid-sensitive substrates may require an additional purification step involving treatment of the distilled TFDA with sufficient Et3N to remove the acid impurity. Other trialkylsilyl fluorosulfonyldifluoroacetates can also be prepared, and they have been found to have reactivities similar to TFDA. The triethyl derivative, TEFDA is more convenient to prepare in a pure state and has similar reactivity to TFDA. Thus, it may prove to be a superior reagent.
- Dolbier Jr., William R.,Tian, Feng,Duan, Jian-Xin,Li, An-Rong,Ait-Mohand, Samia,Bautista, Olivia,Buathong, Saiwan,Baker, J. Marshall,Crawford, Jen,Anselme, Pauline,Cai, Xiao Hong,Modzelewska, Aneta,Koroniak, Henryk,Battiste, Merle A.,Chen, Qing-Yun
-
p. 459 - 469
(2007/10/03)
-
- A novel and highly efficient synthesis of gem-difluorocyclopropanes
-
(Formula presented) A new and highly versatile source of difluorocarbene is reported. Trimethylsilyl fluorosulfonyldifluoroacetate (TFDA) undergoes decomposition in the presence of catalytic fluoride to form difluorocarbene under conditions that allow its addition to relatively electron deficient alkenes in high yield. For example, unprecedented CF2: addition to n-butyl acrylate proceeded in 73percent yield.
- Tian, Feng,Kruger, Virginie,Bautista, Olivia,Duan, Jian-Xin,Li, An-Rong,Dolbier Jr., William R.,Chen, Qing-Yun
-
p. 563 - 564
(2007/10/03)
-