Synlett 2009(19): 3221-3223  
DOI: 10.1055/s-0029-1218382
SPOTLIGHT
© Georg Thieme Verlag Stuttgart ˙ New York

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;

Further Information

Publication History

Publication Date:
13 November 2009 (online)

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

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.

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.

Scheme 1

Abstracts

(A) Adehydes and ketones can be selectively methylenated in the presence of less electrophilic carbonyls groups such as esters [¹a] [5] and amides. [6]

(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.

(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.

(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]

(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]

(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.

(G) The Petasis reagent has been utilized in a tandem methylen­ation-claisen rearrangement to give ring extension [¹6] or contraction. [¹7]

(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]

(I) A one-pot methylenation-RCM procedure has been developed by Nicolaou [²0] using Petasis reagent as both methylenation reagent and RCM catalyst.

(J) A one-carbon homologation was achieved using Petasis methylenation followed by acid hydrolysis. [²¹]

Scheme 1