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New Insights Into the Mechanism of Alkene Metathesis

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New Insights Into the Mechanism of Alkene Metathesis ACADEMIA ROMÂNĂ Rev. Roum. Chim., Revue Roumaine de Chimie 2011, 56(4), 299-316 http://web.icf.ro/rrch/ Dedicated to Professor Alexandru T. Balaban on the occasion of his 80th anniversary REVIEW NEW INSIGHTS INTO THE MECHANISM OF ALKENE METATHESIS Carmen I. MITAN,* Valerian DRAGUTAN and Ileana DRAGUTAN Institute of Organic Chemistry, Roumanian Academy, Spl. Independentei, 202 B, sect. 6, Bucharest, Roumania Received September 8, 2010 The diversity of alkene metathesis reactions, presently applied to their full potential in synthesis of complex scaffolds and assemblies or as key steps in the total synthesis of natural products, demands a deep understanding of the intricate metathesis mechanism since not all of the catalysts are efficient for all of the substrates, nor do they trigger the identical mechanistic pathways, though they share the same main intermediates (the generally accepted metallacarbene and metallacyclobutane). Beyond that, metathesis processes are occasionally complicated by the occurrence of side reactions resulting in a number of by-products. Unveiling the influence of reaction conditions, and in particular of the catalytic system and the active species generated thereof during metathesis of a chosen substrate is paramount for obtaining high yields in the targeted product, at low costs. This paper focuses on relevant kinetic and mechanistic aspects reported to date for alkene metathesis induced by Ru-alkylidene complexes, concentrating on the interplay ligand dissociation – initiation step – overall catalytic activity, as determined by the catalyst structure. INTRODUCTION∗ Metathesis encompasses a range of well- established synthetic methodologies such as ring- Alkene metathesis is basically a catalytic closing metathesis (RCM), ring-opening metathesis transalkylidenation reaction formally occurring by (ROM), cross-metathesis (CM), enyne metathesis scission of two olefinic carbon-carbon double bonds (EM), acyclic diene metathesis (ADMET) and ring- with formation of two new C=C bonds (Scheme 1).1 opening metathesis polymerization (ROMP). Continuously improved activity and selectivity of Presently alkene metathesis is expanding beyond catalysts (especially those based on W, Mo and Ru), these traditional reactions towards less conventional, and the availability of a number of commercial highly innovative and promising pathways such as initiators, have revolutionized the metathesis field asymmetric ring-closing metathesis (ARCM), during the past two decades promoting this reaction asymmetric ring-opening metathesis (AROM), ring- to its current status of a prime mover in organic opening cross metathesis (ROCM), ring-closing synthesis, polymer chemistry, materials science etc., enyne metathesis (RCEYM), ring-rearrangement as largely illustrated in authoritative books,2 book metathesis (RRM), ring-closing alkyne metathesis chapters3 and excellent reviews.4-6 (RCAM), alternating ring-opening metathesis polymerization (AROMP). A B X In the context of the intense progress in A B M organometallic chemistry and catalysis a great deal + + of transition metal complexes have been employed A B as metathesis catalysts.7 Starting primarily with ill- A B defined systems (based on W, Mo),8 this class Scheme 1 – General Representation of Alkene Metathesis. moved quickly to the more efficient metal ∗ Corresponding author: [email protected] 300 Carmen I. Mitan et al. alkylidenes of which Schrock’9 and Grubbs’2a olefin metathesis catalysts is essentially influenced catalysts have gained unanimous recognition. More by the choice of the metal and ligands.35 specific tasks could be additionally achieved with a host of finely elaborated ruthenium-based precursors recognized either by the name of their THE MECHANISM OF ALKENE 10,11 12,13 14 promoters (Blechert, Grela, Nolan, METATHESIS CATALYZED Verpoort15 or by the particular ligands (actor or 16-20 BY RUTHENIUM ALKYLIDENE ancillary) they incorporate, e.g. NHC, Schiff CATALYSTS base,21-25 arene,26 indenylidene,27,28 allenylidene29,30 etc. Most developed representatives soon saw The Hérisson-Chauvin olefin metathesis promotion through several generations (e.g. Grubbs st rd mechanism involves the formation of a 1 to 3 generation), which parallel changes in metallacyclobutane intermediate by coordination of ligands and correspond to an improvement in their the olefinic substrate onto a transition catalytic performance in view of commercialization. metallacarbene complex (Scheme 2).31b The The metal-catalyzed formation of a new C=C generally accepted catalytic cycle of transition metal bond between two olefins occurs under mild catalyzed the formation of a new double bond reaction conditions with high control over factors consists in a reversible sequence of [2+2] such as chemo-, region-, and stereoselectivity cycloadditions – cycloreversion, i.e.:36 alkene (Scheme 1).31 While Schrock type catalysts,32 Mo- coordination to the metallacarbene complex, imido alkylidenes, offer advantages of their high cycloaddition, and cycloreversion to the/a new activity and enantioselectivity, Grubbs type alkene and metallacarbene by breaking of two catalysts,33 Ru-alkylidene, offer high tolerance of different bonds. The newly formed metallacarbene functional groups, air stability and are easy to complex, after coordination with a new olefin handle. Ruthenium-alkylidene complexes with molecule, metallacyclobutane formation, and double general formula [(PR )(L)Cl Ru=CHR’] require bond reordering, gives the metathesis product and 3 2 re-forms the ruthenium carbene initiator which one ligand loss, respectively the trialkyl phosphine restarts the cycle. As the product no longer PR3, to generate the catalytic “active species” participates in the catalytic cycle, the equilibrium is [(L)Cl2Ru=CHR’] with a vacant coordination site thus shifted towards formation of further product able to interact with an olefin substrate. The active molecule (Scheme 2). According to the principle of 6 species, of the d -Ru(II)-based catalyst are detailed balance (PDB),37 at equilibrium the reverse d4-Ru(IV) metal complexes with basic ligands and forward rates of all chemical reactions or all which display a preference for soft Lewis bases elementary steps involved are identical, and the and π-acids (olefins) over hard bases (oxygen reverse reaction proceeds through the same series of containing compounds: alcohols, amides, elementary steps as the forward reaction. aldehydes, carboxylic acids).34 The efficiency of 1 3 1 1 R R 1 3 R R 2 R R R LnM 4 3 2 R 2 R R R R 2 R4 LnM 4 3 + R H R H H LnM 4 LnM R R R H R R 1 1 R R R H R 3 2 R 2 R R R4 1 1 1 1 R R 1 2 R R R R LnM LnM 2 2 2 R 2 R R 1 R R LnM R 1 R 3 + R 3 R 2 LnM 4 4 R 2 R 1 3 R R 3 R 4 R R 4 R 2 R Scheme 2 – General Mechanism of Metathesis Catalyzed by Transition Metal Carbenes. New insights into the mechanism of alkene metathesis 301 PR 3 Cl path 4 Cl Ru PR 3 (Da)cis PR 3 Cl PR PR 3 Cl Ru 3 Cl Cl Ru path 5 Ru path 1 PR3 Cl (C )cis Cl (D2)cis + olefin (Ba)cis 2 - PR 3 PR PR PR 3 Cl PR 3 Cl 3 Cl 3 Cl path 2 Ru Ru path 6 Cl Ru Cl Ru Cl - PR3 + olefin PR Cl (C1)cis 3 (D1)cis (B) path 9 (A) PR path 3 3 Cl path 7 PR3 Cl + olefin Ru PR Ru 3 Cl Cl Cl (C) (D) Ru path 8 Cl - PR3 + PR PR3 3 PR3 Cl PR3 (Ba)trans Cl R3P Ru R3P Ru Cl Cl (C )trans (D )trans a a Scheme 3 – Postulated Mechanisms for Olefin Metathesis with Grubbs-type. Ruthenium Carbene Complexes (J. Am. Chem. Soc. 2004, 126, 3496). As can be seen in Scheme 3, in the case of complexes (C). The calculated activation energies diphosphane ruthenium carbene complexes ∆E# indicate as favorable two reaction pathways: [(PR3)2Cl2Ru=CHR’], two competing pathways (1) the dissociative pathway 2 proceeding through were proposed for the first step of the mechanism: formation of the 14 electron complex (B) with (i) a dominant one (“dissociative”) proceeds by an subsequent coordination of the olefin trans to the initial loss of PR3 to generate a 14-electron phosphane ligand (C), and (2) olefin metathesis is intermediate (B), followed by coordination of the initiated by a trans associative exchange of the olefinic substrate (path 2), or else first coordination phosphane ligand by the olefin (path 3). For both of the olefinic substrate followed by loss of PR3 possibilities, metallacyclobutane formation (path ligand (path 1, and path 3), and (ii) a minor 7) leads to the trigonal bipyramidal pathway (“associative”) in which the olefin metallacyclobutane intermediate (D).39 The barrier coordinates to the catalyst to form an 18-electron difference for the intramolecular cycloaddition olefin π complex (Ba), followed by [2+2] reaction was connected to carbene ligand rotation. cycloaddition (path1/4).38,39 In an early study on Diamagnetic complexes of transition metals with mechanism performed by Grubbs and Sanford, the partially occupied d-orbitals (d2 to d8) generally first step of the second dissociative pathway (path maintain their geometry upon ligand removal. The 1, and path 3) was also named associative.40 The Ru(II) intermediate in metathesis catalysis can be rate determining step, metallacycle formation, is a classified as pseudo-octahedral, with a free 14-electron complex in the “dissociative” pathway coordination site occupying the sixth vertex, and and a 16-electron complex in the “associative” Ru(IV) as a pentagonal bipyramid with two free pathway.38 The coordination of olefin may occur coordination sites in the pentagon close to the cis (path 5 and 6) or trans (path 7) relative to the spectator ligand L (Fig. 1).41 phosphane ligand in the 16-electron olefin π 302 Carmen I. Mitan et al. L L H Ru X Ru X H L ' Ru(II), d6-ML 4 5 Ru(IV), d -ML5 16-valence electrons 14-valence electrons one formally two formally coordination site coordination sites Structure derived Structure derived from from octahedron pentagonal bipyramid Fig.
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