nBuLi and tBuLi can take part in halogen metal exchange OR deprotonate. Is there any way to predict which it favours?

[![enter image description here](https://i.stack.imgur.com/Kw6gz.png)](https://i.stack.imgur.com/Kw6gz.png)


I have included a synarchive pathway: <https://synarchive.com/syn/144> where BuLi favours deprotonation over halogen metal exchange




According to [Bordwell $\mathrm{p}K\_\mathrm{a}$ Table](https://organicchemistrydata.org/hansreich/resources/pka/), $\mathrm{p}K\_\mathrm{a}$ of $\ce{PhCH2COSPh}$ is $16.9$, which is compatible with alcoholic $\ce{OH}$. We all know that Grignard reagents and organolithium reagents are very susceptible to acidic hydrogens because they are strongly basic as well as nucleophilic. Between $\ce{t-BuLi}$ and $\ce{n-BuLi}$, $\ce{t-BuLi}$ is considered to be acting as base than nucleophile compared to $\ce{n-BuLi}$, due to its bulkiness. However, both of them are known for their capability of metal-proton exchange (e.g., see [Wikipedia](https://en.wikipedia.org/wiki/Tert-Butyllithium)).


On the other hand, lithium-halogen exchange reactions are kinetically controlled. The position of the equilibrium varies with the stabilities of the carbanion intermediates involved $\mathrm{(sp >> sp^2 >> sp^3)}$, rather than whether it is $\ce{n-BuLi}$ or $\ce{t-BuLi}$. Keep in mind that lithium-halogen exchange reactions using alkyl-lithium typically employ two or more equivalents of alkyl-lithium reagent. The first equivalent is used for the exchange and the second equivalent reacts with the alkyl-I produced to form corresponding alkane, alkene, and lithium iodide (e.g., Ref.1). Nevertheless, if acidic hydrogen is available, the reaction goes through metal-proton exchange.


Note that the scheme given in [Synthesis of Aplysin](https://synarchive.com/syn/144), part of which OP has copied is somewhat misleading. When you look at the original reference (Ref.2), it is clear that their intention wasn't halogen-metal exchange. It is clearly to use the lithium reagent as a base:


[![Scheme 2 of Ref.1](https://i.stack.imgur.com/F9GHJ.jpg)](https://i.stack.imgur.com/F9GHJ.jpg)


It indicated that $\ce{t-BuLi}$ is added to the compound $\bf{12}$ at $\pu{-78 ^\circ C}$, waited $\pu{10 min}$ before adding 4-iodobutene, and then let the solution warm up to $\pu{0 ^\circ C}$. After $\pu{5 h}$ at room temperature, the yield of the compound $\bf{13}$ was still only $48\%$ (see the red box). The ref.2 did not mention what was the other $52\%$. It may be a combination of nucleophilic addition and halogen exchange. I'm just speculating.




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An example for use of $\ce{n-BuLi}$ for halogen-metal exchange is given in Ref.3.


**References:**


1. Helmut Neumann, and Dieter Seebach, "Stereospecific preparation of terminal vinyllithium derivatives by Br/Li-exchange with *t*-butyllithium," *Tetrahedron Letters* **1976**, *17(52)*, 4839-4842 (DOI: <https://doi.org/10.1016/S0040-4039(00)78926-X>).
2. David C. Harrowven, Matthew C. Lucas, and Peter D Howes, "Total syntheses of aplysin and debromoaplysin using a diastereoselective, sulfur mediated radical cyclisation strategy," *Tetrahedron Letters* **1999**, *40(23)*, 4443-4444 (DOI: <https://doi.org/10.1016/S0040-4039(99)00768-6>).
3. Donald F. Hoeg, Donald I. Lusk, and Alvin L. Crumbliss, "Preparation and Chemistry of α-Chloroalkyllithium Compounds. Their Role as Carbenoid Intermediates," *J. Am. Chem. Soc.* **1965**, *87(18)*, 4147–4155 (DOI: <https://doi.org/10.1021/ja01096a025>).


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