We also screened other metal triflate catalysts for their catalytic activity and found them to be effective in most cases (). However, gallium triflate was found to be the most useful giving the highest yield of products (, entry 1). The reaction with neodymium triflate (, entry 8) was incomplete, giving a mixture of the corresponding imine and the α-aminonitrile product. These results point toward the need of the proper catalyst and solvent system (suitable metal triflate as a catalyst and dichloromethane as a solvent in present cases), which play the key role for the success of the reaction. In earlier studies (–), acetonitrile and toluene were used as solvents; however, these are not suitable for the Lewis acid catalyzed direct Strecker reaction of ketones due to their interaction with the catalyst. The use of dichloromethane minimizes such interaction, resulting in enhanced catalytic activity of the catalyst toward ketones and providing a suitable environment for the reaction.
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Our method is also feasible with aliphatic fluorinated ketones. However, it is interesting to note that, with aromatic trifluoromethyl ketones such as 1,1,1-trifluoroacetophenone, instead of the expected three-component reaction product, the trimethylsilyl-protected fluorinated cyanohydrin derivative (TMSCN addition product from 1,1,1-trifluoroacetophenone) was obtained. Hence, success of the overall reaction depends on the rate of the two possible routes; initial aminal/imine formation and the TMSCN addition to ketones. It is probable that, in the case of the aliphatic fluorinated ketones, the rate of initial aminal/imine formation is fast compared with the rate of the cyanohydrin adduct formation and subsequently the desired products from three-component reaction were formed predominantly. However, in the case of 1,1,1-trifluoroacetophenone and its derivatives, the rate of the cyanohydrin adduct formation is higher compared with the rate of aminal or imine formation; hence, the TMS protected cyanohydrin adduct was observed instead of the three-component reaction product. shows the results of the Strecker reaction for different fluorinated ketones and a variety of amines. One major advantage of this procedure is that no further purification is needed, thus avoiding tedious chromatography and loss of products during purification. The products are obtained in very high yield and purity.
GALLIUM TRIFLUOROMETHANESULFONATE | Gelest, Inc.
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Green chemical processes play a crucial role in sustainable development, and efficient recyclable catalysts that can be conveniently applied in various chemical reactions are the key elements for the development of sustainable synthetic processes. Many organic transformations rely on Lewis and Brønsted acid catalysts, and such molecules have been widely studied in organic synthesis. Over the years, researchers have looked for Lewis acid catalysts that provide high selectivity and high turnover frequency but are also stable in aqueous media and recoverable. Since the first preparation of trifluoromethanesulfonic acid by Hazeldine (triflic acid, HOTf), researchers have synthesized and used numerous metal triflates in a variety of organic reactions. Even though the rare earth metal triflates have played a major role in these studies, the majority of rare earth triflates lack one or more of the primary properties of sustainable catalysts: low cost and easy availability of the metals, easy preparation of triflates, aqueous/thermal stability, recyclability, and catalytic efficiency.