Rearrangement Pummerer

The Pummerer rearrangement is the formation of cr-acyloxythioethers by the transformation of sulphoxides using acetic anhydride. The sulfur is reduced with concommitant oxidation of the a-carbon. 

The Pummerer rearrangement was reported by Rudolf Pummerer in 1909 when he published a paper in Chemische Berichte. Earlier in the same year, Smythe had reported the reaction of dibenzyl sulfoxide 3 with acetic anhydride and hydrochloric acid to give benzaldehyde 4 and thioacetal 5, among other products. Smythe was apparently unable to explain the product distribution, which was then left to Pummerer do so in his much-cited paper later that year. Pummerer published the reaction of sulfinyl acetic acid 6 with hydrochloric acid to give glyoxylic acid 7. The formal oxidation of the 

Pummerer wrote only one further paper on this chemistry, in 1910. The reaction of sulfoxide 11 with acetic anhydride was shown to afford sulfide 12 in what is now recognised as the classical Pummerer rearrangement. From these two reports, the scope of the Pummerer rearrangement has been investigated by many prominent groups who have spent much time and effort in extending the utility of this illustrious reaction. This is perhaps best exemplified by the considerable number of reviews on the Pummerer rearrangement.  

More recently, two distinct mechanistic pathways for the Pummerer rearrangement have been described. These are the vinylogous Pummerer pathway, and the additive Pummerer sequence. The vinylogous pathway 

The additive Pummerer sequence proceeds via an SN2-like displacement, that is, nucleophilic attack and alkoxide departure take place in a concerted manner. This pathway has been utilized more recently for the formation of heteroatom-carbon and carbon-carbon bonds, particularly in the synthesis of polycyclic natural products and drug-like molecules. 

The mechanism of the Pummerer rearrangement consists of four steps 1) acylation of the sulfoxide oxygen to form an acyloxysulfonium salt 2) loss of a proton from the a-carbon to afford an acylsulfonium ylide 3) cleavage of the sulfur-oxygen bond to give sulfur-substituted carbocation (RDS) and 4) capture of the nucleophile by the carbocation. 

Quartromicins are complex C2 symmetric macrocyclic natural products that have significant activity against a number of human viral targets.The diastereoselective synthesis of the endo- and exo-spirotetronate subunits of the quartromicins was accomplished by W.R. Roush and co-workers. The preparation of the exo-a-acetoxy aldehyde involved the Pummerer rearrangement oi a sulfoxide using acetic anhydride as the activating reagent and NaOAc as the co-catalyst. The yield of this transformation was modest and all attempts to improve its efficiency failed. 

The total synthesis of (+)-deethylibophyiiidine was achieved by J. Bonjoch et ai. using a tandem Pummerer rearrangement/thionium ion cyclization to generate the quaternary spiro center.The suifoxide was exposed to an equimoiar mixture of TFA/TFAA and heated for 2h to form the quaternary stereocenter at C7 with the desired stereochemistry, but at C6 a mixture of epimers were formed. Reductive desuifurization with Raney-Ni followed by photochemical rearrangement afforded the natural product. 

The transformation of sulfoxides into a-acyloxythioethers using acetic anhydride. 

Pummerer, R. Ber. Dtsch. Chem. Ges. 1910, 43, 1401. Rudolf Pummerer, bom in Austria in 1882, studied under von Baeyer, Willstatter, and Wieland. He worked for BASF for a few years and in 1921 he was appointed head of the organic division of the Munich Laboratory, fulfilling his long-desired ambition. 

Matsuda, H. Fujita, J. Morii, Y. Hashimoto, M. Okuno, T. Hashimoto, K. Tetrahedron Lett. 2003, 44, 4089. 

Name Reactions, 4th ed., DOI 10.1007/978-3-642-01053-8 210, Springer-Verlag Berlin Heidelberg 2009 

Pummerer rearrangement. In Name Reactions for Homologations-Part IP, Li, J. J., Corey, E. J., Eds. Wiley Sons Hohoken, NJ, 2009, pp 334-352. (Review). 

Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications, DOI 10.1007/978-3-319-03979-4 225, Springer International Publishing Switzerland 2014 

Phosphorus, Sulfur Silicon Relat. Elem. 1991,120 121, 145. 

Marchand, P. Gulea, M. Masson, S. Averbuch-Pouchot, M.-T. Synthesis 2001, 1623. 

Ramberg, L. Backlund, B. Arkiv. Kemi, Mineral Geol 1940,13A, 50. 

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Sharpless and Masumune have applied the AE reaction on chiral allylic alcohols to prepare all 8 of the L-hexoses. ° AE reaction on allylic alcohol 52 provides the epoxy alcohol 53 in 92% yield and in >95% ee. Base catalyze Payne rearrangement followed by ring opening with phenyl thiolate provides diol 54. Protection of the diol is followed by oxidation of the sulfide to the sulfoxide via m-CPBA, Pummerer rearrangement to give the gm-acetoxy sulfide intermediate and finally reduction using Dibal to yield the desired aldehyde 56. Homer-Emmons olefination followed by reduction sets up the second substrate for the AE reaction. The AE reaction on optically active 57 is reagent... 

All of these ehimnddon reacdons contain fi-carbonyl groups in the nltro compounds Of course, masked carbonyl groups are also frequently employed for such fi-elimination of HNO, as shown in Eq 7131, Eq 7 133, and Eq 7 133In these cases, the sulfinylmethyl or hydroxymethyl group is converted into the carbonyl group by the Pummerer rearrangement or by simple oxidation... 

Recently, the Pummerer rearrangement has been employed also in the 2//-selenopyran synthesis (93CC577). 

Chlorotrimethylsilane-induced Pummerer rearrangements effect the transformation of 4-ketothiane oxides into the corresponding a, /1-unsaturated thianes348, apparently via the formation and subsequent deprotonation of thiiranium intermediates rather than by the conventional sulfocarbonium mechanism depicted in equation 129. 

An intramolecular version of enolate Michael addition to enantiomerically pure vinylic sulfoxides is represented by reaction of a cyclopentenone sulfoxide with dichloroketene (Scheme 5)90 this type of additive Pummerer rearrangement has been developed by Marino and coworkers91 into a highly effective way of constructing variously substituted lactones in very high enantiomeric purity (equation 43). 

Prostaglandins 624, 725, 960 Prostanoids 620 Protonation 565-567, 1049 photochemical 882 Pseudopotential methods 15, 16 Pummerer rearrangement 240, 243, 470, 843 Pyramidal inversion 602, 604 Pyrazolenines 749 Pyridazine oxides 640 Pyridine aldehydes, synthesis of 310 Pyridine oxides 640 Pyrolysis 102-105 of sulphones 110, 679-682, 962 of sulphoxides 739, 740 Pyrroles 265, 744... 

Cyclization of the sulfoxide 1248 with TMSOTf 20/DlPEA affords a 4 1 mixture of the tetrahydroquinolines 1249 and 1250, in 97% yield, and HMDSO 7 [49]. On heating of the sulfoxide 1251 to 80 °C Brook rearrangement then Sila-Pummerer rearrangement-cyclization gives, via 1252, 17% 1253 [50] (Scheme 8.19). 

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