Alkynes: not just your grandpa’s sp nucleophile anymore

Hoveyda and crew at Boston College have recently published a paper on asymmetric alkylations of alkynyl pyridinyl ketones with zinc reagents and some amino-acid-derived catalysts. The paper contains quite literally a list of reasons why they concentrated on alkylations of ynones specifically, chief among which is the buttload of heterocyclization research that has been done lately with alkynes. That’s what I’m going to concentrate on in this post, although Hoveyda’s paper is rather interesting.

Way back in the dark ages of chemistry that were the early 1980’s, organometallic chemists discovered and characterized the first vinylidene and allenylidene complexes of rhodium. Picture allene, then cut out one of the end carbons and replace it with rhodium, Fischer-carbene style. Voila vinylidene! These complexes could be made by tossing a square planar rhodium complex in with, oddly enough, a terminal alkyne. Isotopic studies showed that the mechanism of the transformation from alkyne to vinylidene involved a migration of hydrogen from the end of the alkyne one carbon over, to the carbon end of the vinylidene:
Sitting right smack in the middle of two leave-alicious double bonds, the central carbon atom of these vinylidene complexes turns out to make a nice electrophile. In 1996, Frank McDonald of Northwestern used this unique reactivity to synthesize dihydrofurans. Check out this gorgeous catalytic cycle!
These kinds of substrates can be used for carbon cyclizations too, when the nucleophile involved is a double bond. Exactly how the double bond gets put back in place has been debated, but I’d put money on something like electrophilic aromatic substitution–the double bond attacks, then elimination occurs to regenerate it (by the anionic metal, perhaps?). See below.

Since all of this work with hydrogen-terminated alkynes, people have figured out that the migrating group need not be hydrogen: halogens, silanes, and even germanes migrate too! Rhodium, gold, and tungsten have all been used to effect these migrations. In 2006, Gevorgyan and Seregin used gold in conjunction with pyridinyl ynones, observing the first germane migration and forming fused pyridine heterocycles via vinylidenes. And now, thanks to Hoveyda, there’s an easy way to make the substrates for their reaction enantiomerically pure. Hooray!

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