Grob fragmentation

In chemistry, a Grob fragmentation is an elimination reaction that breaks a neutral aliphatic chain into three fragments: a positive ion spanning atoms 1 and 2 (the 'electrofuge'), an unsaturated neutral fragment spanning positions 3 and 4, and a negative ion (the 'nucleofuge') comprising the rest of the chain. In chemistry, a Grob fragmentation is an elimination reaction that breaks a neutral aliphatic chain into three fragments: a positive ion spanning atoms 1 and 2 (the 'electrofuge'), an unsaturated neutral fragment spanning positions 3 and 4, and a negative ion (the 'nucleofuge') comprising the rest of the chain. For example, 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: The reaction is named for the Swiss chemist Cyril A. Grob. An early instance of fragmentation is the dehydration of di(tert-butyl)methanol yielding 2-methyl-2-butene and isobutene, a reaction described in 1933 by Frank C. Whitmore. This reaction proceeds by formation of a secondary carbocation followed by a rearrangement reaction to a more stable tertiary carbocation and elimination of a t-butyl cation: Albert Eschenmoser in 1952 investigated the base catalysed fragmentation of certain beta hydroxy ketones: The original work by Grob (1955) concerns the formation of 1,5-hexadiene from cis- or trans-1,4-dibromocyclohexane by sodium metal: According to reviewers Prantz and Mulzer (2010), the name Grob fragmentation was chosen 'in more or less glaring disregard of the earlier contributions'. The reaction mechanism varies with reactant and reaction conditions with the fragmentation taking place in a concerted reaction or taking place in two steps with a carbocationic intermediate when the nucleofuge leaves first or taking place in two steps with an anionic intermediate when the electrofuge leaves first. The carbanionic pathway is more common and is facilitated by the stability of the cation formed and the leaving group ability of the nucleofuge. With cyclic substrates, the preferred mode of elimination is anti. An example of a Grob-like fragmentation in organic synthesis is the expansion of the Wieland–Miescher ketone to thapsigargin: