Mechanistic and Sterochemical Insights on the Pt-Catalyzed Rearrangement of Oxiranylpropargylic Esters to Cyclopentenones Ada ́ n B. Gonza ́ lez-Pe ́ rez, Bele ́ n Vaz, Olalla Nieto Faza,* and A ́ ngel R. de Lera* Departamento de Química Orga ́ nica, Facultade de Química, Universidade de Vigo, 36310 Vigo, Spain. * S Supporting Information ABSTRACT: A mechanism for the rearrangement of oxiranylpropargylic esters to cyclopentenones catalyzed by PtCl 2 is proposed based on DFT calculations (M06/6-31++G(d,p)). Although the basic steps are coincidental with those proposed by Sarpong et al., who characterized a 2H-pyran as intermediate, calculations have revealed other intricate details of this complex rearrangement. The 2H-pyran is proposed to result from the ring- opening of a bicyclic oxonium ion that follows the nucleophilic capture by the epoxide of a platinum carbene generated by an initial Pt-mediated 1,2-propargylic rearrangement. The key steps in the evolution of this system are the electrocyclic ring-opening of the 2H-pyran to a α-methoxycarbonyl dienone and an iso-Nazarov ring closure. Prior to those, changes in hapticity and in the conformation of the dienone are required in order to produce the helical conformation needed to generate a single diastereomer of the cyclopentenone product obtained experimentally. The metal is needed well beyond the first step of the mechanism, and both electrocyclic reactions are favored by coordination to the metal when compared to their uncomplexed counterparts. Moreover, we have experimentally demonstrated that the rearrangement is stereoconvergent, a feature that is traced back to the initial configuration of the epoxide, which determines the somewhat counterthermodynamic placement of the metal syn to the methyl group of the stereogenic center in the 2H-pyran intermediate. Finally, starting from enantiopure oxiranylpropargylic ester 13, a racemate of cyclopentenone (R*,S*)-16 was obtained. Thus, the sequence does not proceed with memory of chirality, and the absolute stereochemical information is already lost at the stage of the 2H-pyran 14. ■ INTRODUCTION The use of gold and platinum complexes in homogeneous catalysis has experienced an unprecedented development in the past decade. These new synthetic tools exploit the properties of noble metals as activators of carbon-carbon π-bonds func- tioning as soft, carbophilic Lewis acids in reactions that achieve a large increase in molecular complexity under mild conditions, compatible with a wide range of functional groups. 1-14 In parti- cular, their application as catalysts in intramolecular skeletal rearrangements has captured the interest of chemists through the provision of an efficient and atom-economical method of generating cyclic compounds with complex structures and a defined configuration. Propargylic esters have been one of the most studied substrates for reactions with gold or platinum, 15 since they are easily available, can be densely functionalized, and offer the possibility of an initial 1,2- or 1,3-ester migration that opens the way to a rich catalytic manifold involving different paradigms of reactivity, resulting in interesting intramolecular rearrange- ments. 16-19 The dual role of the catalyst in this environment rich in functional groups, as both a simple alkynophilic Lewis acid and an organizing metallic center has been proposed and exploited in a large number of recent contributions. 4,20-25 Upon activation of the alkyne by coordination to the metal, the intramolecular nucleophilic attack of the carbonyl in the carboxylate moiety can occur at either termini of the insatura- tion, and this is followed by the propargylic C-O bond cleavage, which completes the 1,2- or 1,3-ester migration. The barriers for these potentially reversible processes are usually low, and the preference for one or another will depend on the functionalization of the reactant and the further evolution of the allene or carbenoid/ carbocationic intermediate thus generated. 26 The most common evolution of this allene or carbenoid or cationic species 1,26-29 is by nucleophilic attack of an external or internal nucleophile. When the internal nucleophile is an olefin (an 1,n-enyne as a reactant), 4,6,30,31 the alkyne-metal complex usually reacts with the alkene to yield exo or endo cyclopropyl carbenes through either a 5-exo-dig or a 6-endo-dig cyclization, respectively, that can further evolve following different rearrangement patterns. In the presence of other nucleophiles, alternative adducts can be formed, and more complex transformations can be achieved starting from more functionalized enynes. 32 This is the case when the alkene is replaced by an oxirane, 33,34 or an aziridine, 35 opening new mechanistic possibilities. Sarpong et al. recently reported an impressive one-pot transformation of oxiranyl propargylic esters such as i to 2-cyclopentenones iii catalyzed by PtCl 2 which occurs with high regio- and diastereoselectivity (see Scheme 1). 36 Received: August 13, 2012 Published: September 10, 2012 Article pubs.acs.org/joc © 2012 American Chemical Society 8733 dx.doi.org/10.1021/jo301651r | J. Org. Chem. 2012, 77, 8733-8743