Grob fragmentation

Grob fragmentation is a chemical elimination reaction that breaks a neutral aliphatic chain into three fragments: a positive ion (the "electrofuge"), an unsaturated neutral fragment, and a negative ion (the "nucleofuge"). This reaction is named after the Swiss chemist Cyril A. Grob[1].

The positive ion may be a carbenium, carbonium, or acylium ion; the neutral fragment could be an alkene, alkyne, or imine; and the negative fragment could be a tosyl or hydroxyl ion[1]. The reaction mechanism can vary depending on the reactant and reaction conditions, with the fragmentation often facilitated by the stability of the cation formed[1].

Grob fragmentation is a useful method for constructing medium or large rings from bicyclic systems[4]. It has been widely used in the synthesis of various compounds, including those derived from terpenes[3]. The reaction can proceed in either stepwise or concerted pathways, though the concerted pathway is typically preferred[10].

The Grob fragmentation is also similar to the pinacol rearrangement. Substrates that are 1,2-diols (or 1,2-diol type compounds) undergo the pinacol rearrangement, while substrates that are 1,3-diols (or 1,3-diol type compounds) undergo the Grob fragmentation[4].

During the fragmentation, two bonds are broken and three fragments are produced: an electrophilic fragment, an alkene, and a nucleofuge[2]. The reaction is facilitated by the stability of the cation formed[1]. The structure and the stereochemistry of the starting compound can have a crucial influence on the outcome of the reaction[3].

Citations:

[1] https://en.wikipedia.org/wiki/Grob_fragmentation

[2] https://www.sciencedirect.com/topics/chemistry/grob-fragmentation

[3] https://pubmed.ncbi.nlm.nih.gov/12633102/

[4] https://chem.libretexts.org/Bookshelves/Organic_Chemistry/Organic_Synthesis_(Shea)/03:_Neighboring_Group_Participation_Rearrangements_and_Fragmentations/3.04:_Fragmentations

[5] https://pubs.acs.org/doi/10.1021/acs.orglett.1c03299

[6] https://pubs.acs.org/doi/pdf/10.1021/ol034083a

[7] https://www.rsc.org/publishing/journals/prospect/ontology.asp?MSID=B801470C&id=RXNO%3A0000111

[8] https://www2.chemistry.msu.edu/faculty/reusch/virttxtjml/rearang2.htm

[9] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6420057/

[10] https://bpb-us-e2.wpmucdn.com/faculty.sites.uci.edu/dist/0/144/files/2012/04/Grob-Fragmentations.pdf

[11] https://pubs.rsc.org/en/content/articlehtml/2016/np/c5np00073d

[12] https://www.sciencedirect.com/topics/chemistry/fragmentation-reaction

[13] https://pubs.rsc.org/en/content/articlelanding/2011/ob/c0ob00632g

[14] https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/fragmentation-reaction

[15] https://scholarworks.uvm.edu/cgi/viewcontent.cgi?article=1426&context=graddis

[16] https://academic-accelerator.com/encyclopedia/grob-fragmentation

[17] https://www.pnas.org/doi/10.1073/pnas.0403300101

[18] http://www.chem.ucla.edu/~harding/IGOC/F/fragmentation~.html