- Kornblum–DeLaMare rearrangement
The Kornblum–DeLaMare rearrangement is a
rearrangement reaction inorganic chemistry in which a primary or secondaryorganic peroxide is converted to the correspondingketone andalcohol underbase catalysis . The reaction is relevant as a tool inorganic synthesis and is a key step in thebiosynthesis ofprostaglandins . ["The base catalyzed decomposition of a dialkyl peroxide" Nathan Kornblum and Harold E. DeLaMare "J. Am. Chem. Soc. "; 1951; 73(2) pp 880 - 881; (DOI|10.1021/ja01146a542)]:
The base can be an
hydroxide such aspotassium hydroxide or anamine such astriethylamine .Reaction mechanism
In the
reaction mechanism for this organic reaction the base abstracts the acidic α-proton of the peroxide 1 to form thecarbanion 4 as areactive intermediate which rearranges to theketone 2 with expulsion of the hydroxyl anion 3'. This intermediate gains a proton forming the alcohol 3.:
Deprotonation and rearrangement can also be aconcerted reaction without formation of 4.An alternative reaction mechanism involving direct
nucleophilic displacement on the peroxide link of the amine followed by anelimination reaction is considered unlikely based on the outcome of this model reaction: ["The mechanism of the tertiary amine catalysed isomerisation of endoperoxides to hydroxyketones: synthesis and chemistry of the intermediate postulated in the peroxide attack mechanism" David R. Kelly, Harjinder Bansal and J. J. Gwynfor Morgan Tetrahedron Letters Volume 43, Issue 51 , 16 December 2002, Pages 9331-9333 doi|10.1016/S0040-4039(02)02374-2]:
The peroxide 1 converts to the hydroxyketone 2 by action of
triethylamine but the alternative route throughhydroxylamine 3 by nucleophilic displacement withLithium diisopropylamide and theammonium salt 4 (bymethylation with methyl trifluoromethanesulfonate) fails.The reaction, formally a rearrangement, ranks under the
elimination reaction s 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.Related reactions
The corresponding reaction involving an
ether is theWittig 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.cope
The original 1951 publication concerned the conversion of "potassium t-butyl peroxide" and "1-phenylethyl bromide" to ultimately
benzophenone andt-butanol withpiperidine as the base:The Kornblum-DeLaMare rearrangement can be carried out as an
asymmetric reaction with a suitable chiral amine such assparteine or acinchona alkaloid: ["Enantioselective Synthesis of -Hydroxyenones by Chiral Base-Catalyzed Kornblum DeLaMare Rearrangement"Steven T. Staben, Xin Linghu, and F. Dean Toste "J. Am. Chem. Soc. "; 2006; 128(39) pp 12658 - 12659; (Communication) (DOI|10.1021/ja065464x)]:
The first step in this
one-pot reaction is 1,4-dioxygenation of 1,3-cycloheptadiene withsinglet oxygen and a TPP catalyst.References
Wikimedia Foundation. 2010.