TheKornblum–DeLaMare rearrangement is arearrangement reaction inorganic chemistry in which a primary or secondaryorganic peroxide is converted to the correspondingketone and alcohol under acid orbase catalysis. The reaction is relevant as a tool inorganic synthesis and is a key step in thebiosynthesis ofprostaglandins.[1]
The base can be ahydroxide such aspotassium hydroxide or anamine such astriethylamine.
In thereaction mechanism for this organic reaction the base abstracts the acidic α-proton of the peroxide1 to form thecarbanion4 as areactive intermediate which rearranges to theketone2 with expulsion of the hydroxyl anion3'. This intermediate gains a proton forming the alcohol3.
Deprotonation and rearrangement can also be aconcerted reaction without formation of4.
An alternative reaction mechanism involving directnucleophilic displacement on the peroxide link of the amine followed by anelimination reaction is considered unlikely based on the outcome of this model reaction:[2]
The peroxide1 converts to the hydroxyketone2 by action oftriethylamine but the alternative route throughhydroxylamine3 by nucleophilic displacement withLithium diisopropylamide and theammonium salt4 (bymethylation withmethyl trifluoromethanesulfonate) fails.
The reaction, formally a rearrangement, ranks under theelimination reactions as already observed by the original authors. Not only alkoxides but anyleaving group capable of carrying a negative charge will do for instance nitrate esters R–C(R)(H)–O–NO2.
The corresponding reaction involving anether is the1,2-Wittig rearrangement. The reaction course in this rearrangement is different because ether cleavage with carbanion formation is unfavorable. ThePummerer rearrangement in one of its reaction step contains a sulfur variation.
The original 1951 publication concerned the conversion ofpotassium t-butyl peroxide and1-phenylethyl bromide to ultimatelyacetophenone andt-butanol withpiperidine as the base:
The Kornblum–DeLaMare rearrangement can be carried out as anasymmetric reaction with a suitablechiral amine such assparteine or acinchona alkaloid:[3]
The first step in thisone-pot reaction is 1,4-dioxygenation of 1,3-cycloheptadiene withsinglet oxygen and aTPP catalyst.