Petasis reagent

Abstract

(A) Adehydes and ketones can be selectively methylenated in the presence of less electrophilic carbonyls groups such as esters1a,5 and amides. [Chemical equation presented] (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. [Chemical equation presented] (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 group11 can also be efficient when an excess of the reagent is used. [Chemical equation presented] (D) The selectivity of this reaction has been extended to unsymmetrical oxalates12 and oxalate monoesters or monoamides. Improvement of the methylenation can be promoted by microwave irradiation.13 [Chemical equation presented] (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 [Chemical equation presented] (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. [Chemical equation presented] (G) The Petasis reagent has been utilized in a tandem methylenation-claisen rearrangement to give ring extension16 or contraction.17 [Chemical equation presented] (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 [Chemical equation presented] (I) A one-pot methylenation-RCM procedure has been developed by Nicolaou20 using Petasis reagent as both methylenation reagent and RCM catalyst. [Chemical equation presented] (J) A one-carbon homologation was achieved using Petasis methylenation followed by acid hydrolysis. 21 [Chemical equation presented] © Georg Thieme Verlag Stuttgart.