Rearrangements Petasis-Ferrier

The aluminum-mediated Petasis-Ferrier rearrangement is a stepwise [1,3]-sigmatropic process. The first step is the coordination of the Lewis-acid to the 0-atom of the enol. Coordination to the ether O-atom is reversible and nonproductive. Cleavage of the adjacent C-O-bond, assisted by the antiperiplanar lone pair of the etheral O-atom, stereospecifically gives rise to an oxocarbenium enolate species, which cyclizes to the desired oxacycle. The rate difference in the rearrangement for the five- versus six-membered series can be explained by the more facile 6-(enolendo)-endo-trig cyclization. The last step is the intramolecular equatorial hydride delivery. 

Similarly, the C22-C26 fully substituted central tetrahydropyran ring of phorboxazole was prepared using the modified Petasis-Ferrier rearrangement. Based on the known mechanistic model, the enol acetal moiety of the rearrangement substrate required the (Z)-configuration. The synthesis of this enol ether was not possible with either the Takai- or Petasis-Tebbe oiefinations. Utilization of the Type-ll Julia olefination afforded the desired enol acetal, but with no /Z selectivity. Upon treatment of these enol ethers with Me2AICI, the rearrangement afforded only the desired tetrahydropyran in excellent yield. 

The first total synthesis of (+)-zampanolide and (+)-dactylolide was achieved in the laboratory of A.B. Smith. The key step of these syntheses was the application of the modified Petasis-Ferrier rearrangement to construct the central c/s-2,6-disubstituted tetrahydropyran moiety in a stereocontrolled fashion. The treatment of the enol acetal with 1 equivalent of Me2AICI at -78 °C effected the rearrangement to furnish the desired c/s-tetrahydropyranone in 59% yield. 

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This reaction is related to the Petasis-Ferrier Rearrangement. 

The same catalyst has been used by this research group in synthesis of j -amino-aldehydes (146) by combining two catalytic reactions, i.e. a Ni(II) complex-catalyzed isomerization of a double bond and a chiral phosphoric acid (127)-catalyzed aza-Petasis-Ferrier rearrangement in a highly dia-stereo- and enantioselective manner (Scheme 39). ... 

Figure 6.75 Examples of anomeric assistance to reactivity, (s.) MOM deprotection (b) Petasis-Ferrier rearrangement...

Smith utilized Petasis-Ferrier rearrangement [17] in the total syntheses of zampanoUde (Sect. 3.2.1) and phorboxazole [18,19]. The l,3-dioxan-4-ones 11 are transformed into 4-methylene-1,3-dioxanes 12, which are treated with Lewis acids to give oxonium intermediates 13. like the Prins reaction described above, the cfs-2,6-disubstituted tetrahydropyran-3-ones 14 are preferentially synthesized via the C - C bond formation (Scheme 5). 

Scheme 5 Preparation of tetrahydropyran via Petasis-Ferrier rearrangement...

The retrosynthetic analysis is outlined in Scheme 22. The amide was introduced by the Curtius rearrangement, and the macrolide 117 was formed by Horner-Emmons macrocyclization at the C2-C3 bond. The C17-C18 bond was constructed by the ring-opening of epoxide 118. 119 was formed via the Kocienski-Julia olefination at the C8-C9 bond. The cis-2,6-disubstituted tetrahydropyran in 120 was constructed by the Petasis-Ferrier rearrangement. The C4-C5 (Z)-trisubstituted alkene in 121 was formed by carbomet-allation to an alkyne. 

The key skeleton of 120 was constructed via the Petasis-Ferrier rearrangement [17], established by Smith as a powerful, stereocontrolled entry to ci5-2,6-disubstituted tetrahydropyran (Scheme 24) [18,19]. Brown asymmetric allylation of the known aldehyde 124 [69] installed the C-11 asymmetric center in 91% ee to give 125 after silylation. Oxidative cleavage of the terminal alkene, followed by silylation, delivered the /8-hydroxy ester 126, which was condensed with aldehyde 127 mediated by TMSOTf (but the actual catalyst was found to be TfOH) to furnish an inseparable mixture of the... 

The catalytic cycle and stereochemical preferences of a stoichiometric variant of the Petasis-Ferrier rearrangement were recently thoroughly studied computationally This enabled the computational study of the reaction catalyzed by chiral BlNOL-based phosphoric acids. ... 

Scheme 7.58 Tandem isomerisation-aza-Petasis-Ferrier rearrangement reaction catalysed by nickel catalysis and chiral phosphoric acid catalysis followed by reduction.

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