Science of Synthesis

Carreira, E. M.; Frantz, D. E., Science of Synthesis: Stereoselective Synthesis, (2011) 2, 498.

Traditional processes to generate nucleophilic metal (i.e., lithium or magnesium) acetylides capable of addition to carbonyl compounds have required an initial deprotonation step using either a strong amide base or alkyllithium at low temperatures to provide the corresponding metalated alkyne in stoichiometric quantities. This preactivation step imparts severe limitations with respect to functional group compatibility, scalability, and catalysis. In contrast, the mild generation of metal acetylides (room temperature and amine base) from copper(I) salts in catalytic cross-coupling methods (i.e., Sonogashira) is a well-known process.[‌8‌] Unfortunately, copper acetylides are in most cases poor nucleophiles toward C=O bonds [copper(I) acetylides, in contrast, can add to imine derivatives[‌9‌]]. In 1991, Yamaguchi was able to demonstrate that tin(II) salts are capable of inducing a mild deprotonation of terminal alkynes with amine bases and that the corresponding tin acetylides can effectively add to aldehydes and ketones (‌Scheme 2‌).[‌10‌]

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References