Petasis Reagent

Carine Vaxelaire

doi:10.1055/s-0029-1218382

Synlett 2009(19): 3221-3223
DOI: 10.1055/s-0029-1218382

SPOTLIGHT

Petasis Reagent

Carine Vaxelaire
Faculté des Sciences Pharmaceutiques et Biologiques, Avenue de l′Observatoire 4, 75270 Paris, France
e-Mail: carine.vaxelaire@univ-paris5.fr;

Abstract

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Biographical Sketches

Carine Vaxelaire was born in Remiremont, France, in 1982. She studied chemistry at the engineering school CPE-Lyon and at the University of Lyon, France. Currently, she is pursuing her Ph.D. under the supervision of Professor Janick Ardisson and Dr. Ange Pancrazi at the Paris Descartes University, France. Her research is focused on the total synthesis of a natural molecule using multistep synthesis.

Introduction

<P>The Petasis reagent [¹] (dimethyl titanocene, Cp₂TiMe₂) is readily prepared by the reaction of methylmagnesium chloride [²] or methyllithium [³] with titanocene dichloride. It is used for transforming carbonyl groups to terminal alkenes, [4] like the Tebbe reagent or Wittig reaction. Unlike the Wittig reaction, the Petasis reagent can react with a wide range of carbonyls, such as aldehydes, ketones, esters, and lactones including enolizable and acid-labile substrates. The Petasis reagent is also non-pyrophoric, relatively air- and water-stable, and can be used directly as a solution in toluene-THF.</P><P>The active olefinating reagent, Cp₂TiCH₂, can be prepared by heating the Petasis reagent in toluene or THF to 60-75 ˚C. The Petasis reaction can also be promoted by microwave irradiation.</P>

Scheme 1

Abstracts

<TD VALIGN="TOP"> (A) Adehydes and ketones can be selectively methylenated in the presence of less electrophilic carbonyls groups such as esters [¹a] [5] and amides. [6] </TD><TD VALIGN="TOP">

</TD><TD VALIGN="TOP"> (B) Reaction of dimethyl titanocene with heteroatom-substituted carbonyls, [¹b] such as silylesters, lactones, [7] thioesters, selenoesters, and acylsilanes gives the corresponding heteroatom-substituted alkenes. </TD><TD VALIGN="TOP">

</TD><TD VALIGN="TOP"> (C) Petasis methylenation can be accomplished in the presence of many protecting groups, like silyl ethers, [8] benzyl ethers, [9] and acetals. [¹0] The reaction in the presence of an unprotected hydroxyl group [¹¹] can also be efficient when an excess of the reagent is used. </TD><TD VALIGN="TOP">

</TD><TD VALIGN="TOP"> (D) The selectivity of this reaction has been extended to unsymmetrical oxalates [¹²] and oxalate monoesters or monoamides. Improvement of the methylenation can be promoted by microwave irradiation. [¹³] </TD><TD VALIGN="TOP">

</TD><TD VALIGN="TOP"> (E) The reaction of β-lactams with Cp₂TiMe₂ can be realized in good yields as long as the lactams are properly activated by N-protection. [¹4] </TD><TD VALIGN="TOP">

</TD><TD VALIGN="TOP"> (F) Homologue dialkyltitanocene derivatives of the Petasis reagent can be prepared from titanocene dichloride and alkyllithium or Grignard reagents, [¹5] with the exception of compounds that undergo facile β-hydride elimination. </TD><TD VALIGN="TOP">

</TD><TD VALIGN="TOP"> (G) The Petasis reagent has been utilized in a tandem methylenation-claisen rearrangement to give ring extension [¹6] or contraction. [¹7] </TD><TD VALIGN="TOP">

</TD><TD VALIGN="TOP"> (H) One application of the Petasis reagent is the Petasis-Ferrier rearrangement, [¹8] which involves methylenation of a 1,3-dioxan-4-one to give an enol ether which yields in the presence of a trialkylaluminium reagent a 2,6-syn-disubstitued tetrahydropyranone. This method has been utilized as an exceptional powerful tool for the total synthesis of complex natural product. [¹9] </TD><TD VALIGN="TOP">

</TD><TD VALIGN="TOP"> (I) A one-pot methylenation-RCM procedure has been developed by Nicolaou [²0] using Petasis reagent as both methylenation reagent and RCM catalyst. </TD><TD VALIGN="TOP">

</TD><TD VALIGN="TOP"> (J) A one-carbon homologation was achieved using Petasis methylenation followed by acid hydrolysis. [²¹] </TD><TD VALIGN="TOP">

</TD>

References

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Few examples:

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Scheme 1