Reaction Mechanisms DOI: 10.1002/anie.201307745 The Pauson–Khand Mechanism Revisited: Origin of CO in the Final Product** Denis Lesage, Anne Milet, Antony Memboeuf, JØrôme Blu, Andrew E. Greene, Jean- Claude Tabet, and Yves Gimbert* Dedicated to Professor GØrard Buono Abstract: The mechanism of the Pauson–Khand reaction has been studied by mass spectrometry and it has been found, through ion-molecule reaction with 13 CO, that the carbon monoxide incorporated into the product cyclopentenone is one that has been retained within the complex. Theoretical and kinetic calculations support this finding, which provides a complementary explanation for the effect of Pauson– Khand promoters. The Pauson–Khand reaction (PKR), a dicobalt-octacar- bonyl-mediated process for joining an alkene, an alkyne, and carbon monoxide to form a cyclopentenone, is a powerful tool for accessing complex molecules. [1] Given the importance of this transformation and the recent advances in theoretical chemistry, it is not surprising that considerable effort has been made over the past few years to establish its mechanism. In their pioneering paper in 2001, Yamanaka and Nakamura [2] presented a mechanistic pathway for the reaction using ethylene and acetylene as model organic partners (Scheme 1, R = R’ = H). This work provided the first theo- retical support for the now widely accepted proposal made by Magnus and Principe in 1985. [3] In their mechanistic pathway, the initially formed and often isolated alkyne dicobalt hexacarbonyl complex of type CP1, after loss of CO and coordination of the alkene, gives a complex of type CP3. The latter undergoes insertion of the alkene to give the key cobaltacycle of type CP4. After the return of the missing CO ligand (complex of type CP5) and insertion, the cobalt acyl complex of type CP6a is produced. The cyclopentenone is finally obtained after extrusion of a [Co(CO) 3 ] fragment from the cobaltacycle and cleavage of [Co 2 (CO) 6 ]. In 2003, we reported the first confirmation, by mass spectrometry, of the existence of the proposed intermediate of type CP4. [4] For that study, the easily deprotonated bridging ligand bis(diphenylphosphino)methane was placed on the neutral dicobalt species to enable facile observation of species in mass spectrometry ion-molecule experiments. A somewhat different approach has now been undertaken to delve into the apparently unquestioned, yet to us quite questionable, return of CO (CP4 !CP5) in the postulated Magnus mechanism. We envisioned a novel study in which the putative incorporation of an external CO at this stage would be examined with 13 CO, again in mass spectrometry ion-molecule experiments. Herein, we disclose the results of this study, which has led to a new, more plausible interpretation of an important facet of the Pauson–Khand transformation. To be able to observe the cyclopentenone final product in ion-molecule experiments, the cationic alkyne salt N-methyl- N-propargylpyrrolidinium hexafluorophosphate [5] appeared ideally suited. The positive ESI mass spectrum [6] of the complex MSCP1 displayed an ion at m/z 410, accompanied by an abundant peak at m/z 382 (100 %), MSCP2, corresponding to the reactive intermediate complex [MSCP1-CO] (Scheme 2). The ion at m/z 382, submitted to a collision activated reaction (CAR) with norbornene, introduced into the modified transfer hexapole H0, yielded an adduct ion at m/z 476, corresponding to [MSCP1-CO + norbornene] . After selection by Q1, this adduct was submitted to a second CAR with CO in the H2 collision cell (see the Supporting Information for experimental details). Scheme 1. Proposed mechanistic pathway for the Pauson–Khand reac- tion (CP designation of Yamanaka and Nakamura [2] ). [*] Prof. A. Milet, J. Blu, Dr. A.E. Greene, Dr. Y. Gimbert UniversitØ Grenoble Alpes (DCM), UMR CNRS-UJF 5250 BP 53, 38041 Grenoble cedex 9 (France) E-mail: Yves.Gimbert@ujf-grenoble.fr Dr. D. Lesage, Prof. J.-C. Tabet UPMC Univ Paris 06 (IPCM), UMR CNRS-7201 4 place Jussieu, 75005 Paris (France) Dr. A. Memboeuf UniversitØ de Brest, CNRS, UMR 6521 6 Av. Le Gorgeu, 29200 Brest (France) [**] Financial support from the CNRS and the UniversitØ Joseph Fourier, and calculation resources provided by CIMENT/CECIC are gratefully acknowledged. Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/anie.201307745. A ngewandte Chemi e 1 Angew. Chem. Int. Ed. 2014, 53,1–5  2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim These are not the final page numbers! Ü Ü