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

Question

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

Answer 1

According to Bordwell $\mathrm{p}K_\mathrm{a}$ Table, $\mathrm{p}K_\mathrm{a}$ 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).

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, 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:

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).