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3.6.14.1.4.3 Method 3: Enantioselective Protonation of Silyl Enol Ethers

DOI: 10.1055/sos-SD-103-00072

Campbell, M. J.; Toste, F. D.Science of Synthesis Knowledge Updates, (20123166.

Another report from Toste shows that a simple catalyst system Au2Cl2[(R)-BINAP]/silver(I) tetrafluoroborate in a mixture of ethanol and dichloromethane is capable of enantioselectively protonating silyl enol ethers to afford the corresponding ketones 73 in high yields and enantioselectivities (Scheme 39).[‌57‌] Preliminary studies showed that five- and six-membered cyclic trimethylsilyl enol ethers are suitable substrates. Enantioselective protonation generates the simple cyclopentanone (93% ee) and cyclohexanone (94% ee), as well as the tetralone (93% ee) and indanone (94% ee) derivatives. In the extension of this method to the protonation of acyclic enol ethers, a class not effectively addressed by previous synthetic methods, it is observed that high selectivities can likewise be obtained. Surprisingly, in experiments conducted with the silyl enol ether of 1,2-diphenylpropan-1-one (72, R2 = R4 = Ph; R3 = Me), the selectivity is independent of the enol ether E/Z ratio; the ratio even shifts during the reaction without any noticeable effect on the enantioselectivity. The aliphatic ketone 73 (R2 = t-Bu; R3 = Me; R4 = Ph) and 1,2-diphenylbutan-1-one 73 (R2 = R4 = Ph; R3 = Et) are both prepared efficiently, but the method fails to discriminate between the methyl and ethyl α-substituents of 72 (R3 = Et; R4 = Me; 17% ee).

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