Petasis-Ferrier rearrangement
The Petasis-Ferrier rearrangement is a name reaction from the field of organic chemistry that was published in 1995 by the Cypriot chemist Nicos A. Petasis . The Petasis-Ferrier rearrangement describes the conversion of an enol acetal into a tetrahydropyranone under the action of a Lewis acid .
Overview
An enol acetal, here with a six-membered heterocycle (R 1 , R 2 = alkyl , aryl radical ), is converted into a tetrahydropyranone , catalyzed by a Lewis acid, here dimethylaluminum chloride:
A rearrangement takes place, whereby an acetal oxygen atom ( marked in blue ) becomes the oxygen atom of the carbonyl group of a ketone.
In addition, the Lewis acids boron trifluoride (BF 3 ), zinc chloride (ZnCl 2 ), TiCl 2 (Oi-Pr) 2 and monomethylaluminum dichloride (AlCH 3 Cl 2 ) can be used.
Alternatively, an identical enol acetal (R 1 , R 2 = alkyl, aryl radical) can be reacted with a trialkyl aluminum, here triethyl aluminum , to form a tetrahydropyranol:
If dimethyl aluminum chloride is used as Lewis acid, the conversion takes place exclusively to tetrahydropyranone and not to tetrahydropyranol.
Reaction mechanism
The following discussion describes a proposal for the reaction mechanism using the example of 2,4-di methyl -6- methylene -1,3-dioxane:
The 2,4-dimethyl-6-methylene-1,3-dioxane ( 1 ) is converted to ( E ) -chlorine ((4- (ethylidenoxonio) pent-1-en-2-yl) oxy) by adding the Lewis acid dimethylaluminum chloride dimethyl aluminate ( 2 ) implemented. After the dimethylaluminum chloride has been split off, 2,6-dimethyltetrahydro-4 H -pyran-4-one ( 3 ) is finally formed .
If the 2,6-dimethyl-tetrahydro-4 H -pyran-4-one ( 3 ) followed by a trialkylaluminum - here triethylaluminum - reduced, there arises a 2,6-dimethyl-tetrahydro-2 H -pyran-4-ol ( 4 ).
Stereoselectivity
The Petasis-Ferrier rearrangement takes place with high stereoselectivity when a chiral enol acetal is used as the starting material . The stereoselectivity of the last step, the reduction of the tetrahydropyranone (or tetrahydrofuranone), depends on the choice of Lewis acid. A trialkylaluminum is necessary for the reduction to take place; when using dimethylaluminum chloride, for example, the reduction does not take place.
Application examples
An example of a synthetic application is the representation of a C3-C19 intermediate for the production of (+) - phorboxazole A:
The substituted tetrahydropyran is reacted with a 2- (alkoxymethyl) oxazole-4-carbaldehyde, dimethylaluminum chloride and the Petasis reagent to form the C3-C19 intermediate for the preparation of (+) - phorboxazole A. Only this isomer of the C3-C19 intermediate of (+) - phorboxazole A is formed.
Individual evidence
- ↑ NA Petasis, S.-P. Lu, J. Am. Chem. Soc. , 1995 , vol. 117, p. 6394.
- ↑ AB Smith, KP Minbiole, PR Verhoest, M. Schelhaas, J. Am. Chem. Soc. , 2001 , Vol. 123, p. 10942.
- ↑ a b c d e f Z. Wang (Ed.): Comprehensive Organic Name Reactions and Reagents, 3 Volume Set , John Wiley & Sons, Hoboken, New Jersey, 2009 , ISBN 978-0-471-70450-8 , p 2173-2174.
- ↑ AB Smith, PR Berhoest, KP Minbiole, JJ Lim, Org. Lett. , 1999 , Vol. 1, p. 909.
- ↑ a b c d e László Kürti and Barbara Czakó: Strategic Applications of Named Reactions in Organic Synthesis: Background and Detailed Mechanisms , Elsevier Academic Press, 2005, pp. 342–343, ISBN 978-0-12-429785-2 .