A New and Efficient Method for the Trifluoromethylation of Carbonyl Compounds with Trifluoromethyltrimethylsilane in DMSO
Katsuyuki Iwanami, Takeshi Oriyama*
*Faculty of Science, Ibaraki University, 2-1-1 Bunkyo, Mito 310-8512, Japan, Email:
tor
mx.ibaraki.ac.jp
K. Iwanami, T. Oriyama, Synlett, 2006, 112-114.
DOI: 10.1055/s-2005-922767
Abstract
In the presence of molecular sieves in DMSO, trifluoromethylation of various aldehydes and ketones with trifluoromethyltrimethylsilane proceeded very smoothly to give the corresponding trifluoromethylated adduct in good to quantitative yields without a base catalyst.
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Details
The document presents a new method for the trifluoromethylation of carbonyl
compounds using trifluoromethyltrimethylsilane (TMSCF3) in DMSO
without a catalyst. This method is significant due to the unique biological
activity of trifluoromethylated compounds, which are valuable in medicinal and
agricultural chemistry. Traditional methods require strong bases or Lewis bases,
which have limitations, especially with aliphatic aldehydes and ketones. The new
method leverages DMSO's ability to activate TMSCF3 through
coordination, facilitating the reaction smoothly and efficiently.
The study found that using molecular sieves (MS) 4 Å as a dehydrating agent
significantly improved yields, achieving quantitative results under optimal
conditions. Various aldehydes and ketones were successfully trifluoromethylated,
with high to quantitative yields, even for sterically hindered substrates. The
reaction conditions are mild, and the process is convenient, not requiring
additional bases or catalysts. The proposed mechanism involves DMSO coordinating
to the silicon atom of TMSCF3, enhancing the nucleophilicity of the
CF3 group, which then reacts with the carbonyl compound.
This method offers several advantages, including broad substrate applicability,
mild conditions, and short reaction times for aldehydes, making it a valuable
addition to synthetic organic chemistry. Further research is ongoing to expand
its scope and applications.
Key Words
trifluoromethylation, trifluoromethyltrimethylsilane, carbonyl compounds, alcohols, DMSO
ID: J60-Y2006-4220
