[Babcock_Hall]

We are following the general procedure in Guan H-G 2007 Synthesis 10:1465-1470. DOI: 10.1055/s-2007-966039  Most of the reactions were carried out in DMF at 80 °C with 1.5 equivalents of sodium phenylsulfinate for 12 hours.  However, one reaction was run in HMPA and triethylamine (Entry 12 in Table 2), but the time and temperature were not provided.  There were also other solvents that were tried (Table 1), but DMF gave the best results under the conditions tested.

We were able to duplicate the results of entries 6 and 4 in Table 2.  We are now attempting this sulfonylation reaction on a substrate in which both bromines are on secondary carbon atoms.  At R¹ in Scheme 1 is a carboxylic ester, and the other carbon of the double bond is an aromatic ring.  Our first attempt took 36 hours for the starting material to disappear.  It led primarily to an alkene that was the precursor of the vicinal dibromide.  We did not see evidence of the product. 

I was thinking about using deuterated DMF and monitoring by H-1 NMR, or of trying the HMPA/TEA conditions.  Unfortunately we have only limited amounts of the vicinal dibromide.  What do people think is most likely to succeed?

[Babcock_Hall]

I am now convinced that the direct conversion of the dibromide to the vinylsulfone will not work.  However, it might be possible first to convert the dibromide to an alkyne with base (Sharaf, S.M. et al., Canadian Journal of Chemistry, 69(9), 1445-9; 1991  https://doi.org/10.1139/v91-213).  Second to convert the alkyne to the vinylsulfone by adding the sulfinic acid across the triple bond (J. Org. Chem. 2016, 81, 10664−10671 DOI: 10.1021/acs.joc.6b01549).  Entry 3la in Table 3 is similar to our molecule of interest.  There is precedent for keeping the ester intact during the elimination.  I am a little concerned about the yield in the second step, which is 55% IIUC.  Thoughts?

[blackcat]

We are following the general procedure in Guan H-G 2007 Synthesis 10:1465-1470. DOI: 10.1055/s-2007-966039  Most of the reactions were carried out in DMF at 80 °C with 1.5 equivalents of sodium phenylsulfinate for 12 hours.  However, one reaction was run in HMPA and triethylamine (Entry 12 in Table 2), but the time and temperature were not provided.  There were also other solvents that were tried (Table 1), but DMF gave the best results under the conditions tested.

We were able to duplicate the results of entries 6 and 4 in Table 2.  We are now attempting this sulfonylation reaction on a substrate in which both bromines are on secondary carbon atoms.  At R¹ in Scheme 1 is a carboxylic ester, and the other carbon of the double bond is an aromatic ring.  Our first attempt took 36 hours for the starting material to disappear.  It led primarily to an alkene that was the precursor of the vicinal dibromide.  We did not see evidence of the product. 

I was thinking about using deuterated DMF and monitoring by H-1 NMR, or of trying the HMPA/TEA conditions.  Unfortunately we have only limited amounts of the vicinal dibromide.  What do people think is most likely to succeed?

1. Secondary bromine reacts slowly than primary.

2. HMPA is not good, not to use it.

3. I do not quite understand the middle paragraph. I think the vincial bromide is the precursor of alkene. What did you really get?

[Babcock_Hall]

In the synthesis, we made an alkene, then we added "Br₂" across the double bond to make a vicinal dibromide, then we attempted to make the sulfone.  Three people have now looked at the NMR, and the consensus is that the majority of the material has returned to being the alkene, which is surprising.

I am beginning to think that the proposed mechanism in the paper might not be correct.  Perhaps the first step is displacement of the bromine on the primary carbon by the sulfinate anion, followed by elimination, and maybe the first step is slower when this attack must take place on a secondary carbon atom.  E2 reactions happen more quickly at secondary than at primary carbons, which suggests to me that the reaction might not be E2 in whatever step controls the rate.

[clarkstill]

I think your mechanstic proposal is at least as plausible as the authors', although I suspect in all cases the eliminations would be E1cb rather than E2 (since R1 is always an EWG in their substrates).
. Sorry I just looked again and saw a bunch of substrates I missed on the first look. Their mechanism definitely isn't the case - the sulfinate would be a terrible base for an E2 reaction, so SN2 of the primary followed by E1cb of the other bromide seems much more reasonable.

However, if the new substituent you've introduced is an arene, then wouldn't the initial SN2 reaction still be pretty fast, since the C-Br is benzylic?

I guess you could also draw a mechanism with some neighbouring group participation, e.g. re-formation of the bromonium ion and ring-opening with the sulfinate, in which case it might go at the secondary (more cationic) position.

I guess your system (something like cinnamic acid?) has a lot of conjugation stabilization, so there's a reasonably big driving force for the elimination of Br2 back to the SM? None of the literature examples were so stabilized.

Sorry this is a bit of a random series of thoughts!

[Babcock_Hall]

Thank you; you made some good points.  Yes, our system is a dimethylester that could be described as a derivative of cinnamic acid.  One question is what to do with the remaining vicinal dibromide.  There is some literature precedent to suggest that it could be eliminated twice to make an alkyne.  One would use methoxide/methanol, presumably to avoid changing the esters into something else.  Then one could add a sulfinic acid to the alkyne to make the vinylsulfone.  If one were starting from scratch, this does not look like the shortest route, however.