Science of Synthesis

Witulski, B.; Alayrac, C., Science of Synthesis, (2006) 24, 947.

The Kowalski reaction is often used to prepare 1-siloxyalk-1-ynes. It is based on the conversion of ethyl esters ‌52‌ into the lithiated bromoenolates ‌53‌, which readily rearrange into ynolates ‌54‌ with the loss of lithium bromide. Subsequent O-silylation of the ynolates with bulky chlorosilanes furnishes 1-siloxyalk-1-ynes ‌55‌ in yields of 50–71% (‌Scheme 17‌).[‌4‌,‌62‌,‌64‌] Mechanistically, the bromoenolates ‌53‌ are generated by the addition of (dibromomethyl)lithium to the ethyl esters ‌52‌, followed by a base-induced elimination reaction. The method is quite general as it is applicable to substrates bearing primary, secondary, or tertiary groups (R1), as well as alkenyl or aryl substituents. Moreover, lactones can be used as starting materials, leading to disilylated ethers.[‌4‌,‌65‌] An improvement in yield is observed when the transformations of the esters ‌52‌ into the products ‌55‌ are performed as a two-step sequence in which the initial dibromomethyl ketone is isolated.[‌25‌] An application of this modification to chiral substrates ‌56‌ proceeds on to the products ‌57‌ without loss of enantiopurity (‌Scheme 17‌).[‌25‌] A related method involves the use of α-chloro-α-sulfinyl ketones, instead of dibromomethyl ketones, as precursors of the ynolates.[‌66‌,‌67‌] Lithium ynolates can also be generated by the thermal cleavage of the dilithium enolates ‌58‌ at 0°C. Yields are about 90%, and the resulting ynolates are then O-silylated with chlorotriisopropylsilane to afford the 1-siloxyalk-1-ynes ‌59‌ (‌Scheme 17‌).[‌68‌–‌70‌] The enolates ‌58‌ are obtained either from α-bromo- or α,α-dibromo esters.

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References

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• 8.Meeeee-Meee, (8888) M 88e8, 8888.
• 8.Meeeee-Meee, (8888) M 88-8, 8888.