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METATHESIS

INTRODUCTION

Since its discovery in the 1960’s, olefin metathesis has been developed to a well established and powerful synthetic tool in organic chemistry and polymer science (1). In contrast, the related alkyne metathesis that involves the breaking and making of carbon-carbon triple instead of double bonds, has been much less investigated, although its mechanism has been proven similar to that of olefin metathesis (Scheme 1) (2). To date only a limited number of species are known to catalyze alkyne metathesis reactions efficiently, despite the high potential for the application of alkyne metathesis in areas such as organic synthesis, pharmaceuticals and materials science (1a, 1l, 3). Therefore, the development of n e w a l k y n e m e t a t h e s i s catalysts with high efficiencies and adequate functional group tolerance is sti l l an important target. In contrast to olefin metathesis catalysts, the homogeneous catalysts for alkyne metathesis are mainly based on two metals – molybdenum (Mo) and tungsten (W) – and can be categorized into three types (Figure 1): The first type,

which is also the first homogeneous catalyst system for alkyne metathesis reactions, was discovered by Mortreux in the mid-1970’s (4). The Mortreux system consists of two components: Mo(CO)6 and phenol additives. Since the active species generated in situ are unknown, this catalytic system must be considered as ill-defined, preventing a rational catalyst design and improvement. Nevertheless, these Mo-based systems are currently widely used for alkyne metathesis reactions because of the high stability and commercial availability of the pre-catalysts. As a drawback, however, these systems can only be employed for the transformation of robust and thermally stable substrates, since high reaction temperatures are generally required. The second type developed by Cummins and Fürstner (5, 6) is also based on molybdenum. In this system, the molybdenum(III) triamido complex [Mo{N(tBu)Ar}3] is activated by treatment with dichloromethane producing [HC:Mo{N(tBu)Ar}3] and [ClMo{N(tBu)Ar}3], whereby the latter one, the chloro complex, was considered to be the active species. Moore has isolated similar complexes such as [EtC:Mo{N(tBu)Ar}3], which can be activated for efficient alkyne metathesis by treatment with phenol derivatives or by capture on silica (7). The nature of the catalytically active species has not yet been fully uncovered. Finally, the third catalyst type comprises well-defined tungsten alkylidyne complexes (8, 9). Catalysts

belonging to this category exhibit high activities in alkyne metathesis reactions; in particular, the neopentylidyne complex [Me3CC:W(OCMe3)3]

represents the most widely used catalyst for alkyne metathesis reactions to date (3a). Until recently, this classical alkylidyne

Development of alkyne metathesis catalystsIt’s a game of give and takeMATTHIAS TAMM*, XIAN WU

*Corresponding authorTechnische Universität Braunschweig, Institut für Anorganische und Analytische Chemie Hagenring 30, 38106 Braunschweig, Germany

ABSTRACT: New Schrock type tungsten alkyl idyne complexes were designed and synthesized through high and low oxidation state routes. In particular, the tungsten alkylidyne complexes 2 and 4 bearing the 1,3-di-tert-butylimidazolin-2-iminato group (ImtBuN) exhibit very high catalytic activities in alkyne metathesis reactions such as alkyne cross metathesis and ring-closing alkyne metathesis. Through the combination of the strong electron-donating imidazolin-2-iminato ligand and the electron-withdrawing fluorinated alkoxide groups, a “Push-Pull-Situation” is established, which is considered to be responsible for the observed high catalytic efficiency. DFT calculations have been used to explain the experimental results and to uncover even more active catalysts.

KEYWORDS: Alkyne metathesis, homogeneous catalysis, catalysts design.

Scheme 1. Olefin metathesis and alkyne metathesis. Figure 1. Different alkyne metathesis catalysts.

It’s a game of give and take

Matthias Tamm

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METATHESIS

(one mol% catalyst loading) was investigated; 2 is able to catalyze this reaction efficiently at both ambient and elevated temperatures (Figure 3) (14, 15). In addition, the catalytic performance of 2 proved to be clearly superior in comparison with the established catalyst system [Me3CC:W(OCMe3)3] (14). The same catalytic reaction was also studied using the tungsten neopentylidyne complexes 5 and 6 (15), which

complex could be regarded as the only catalytically active, well-defined tungsten-based species among all the alkyne metathesis catalysts that have been utilized.

DESIGN AND PREPARATION OF NEW SCHROCK TYPE ALKYNE METATHESIS CATALYSTS

Since the abovementioned catalyst systems still leave substantial room for improvement with regard to their stability towards moisture and oxygen, functional group tolerance and required reaction temperature, new strategies for a rational catalyst design are still required in order to boost the recognition of alkyne metathesis and to overcome the prevalence of olefin metathesis. Recently, our group has introduced imidazolin-2-iminato ligands of type I (Figure 2), which can be used as anci l lary l igands in various homogeneous catalysts (10). These ligands can be described by the two resonance structures IA and IB (Figure 2), indicating that the ability of the imidazolium ring to stabilize a positive charge leads to highly basic ligands with a strong electron-d o n a t i n g c a p a c i t y towards early transition metals. Owing to their abi l i ty to act as 2σ , 4π-electron donors, these ligands can be regarded a s m o n o a n i o n i c analogues of dinegative imido ligands, that are also present as ancillary ligands in some of the m o s t a c t i v e o l e f i n metathes is catalysts , stable molybdenum and t u n g s t e n a l k y l i d e n e complexes of type II. Accordingly, substitution of the imido ligand by mononegative imidazolin-2-imides allows the concurrent conversion of the metal-carbon double bond into a triple bond, affording alkylidyne complexes of type III with well-preserved structural and electronic integrity and therefore with potentially undiminished catalytic activity (Figure 2). Two different preparative routes have been developed, a high oxidation state route starting from WCl6 and a low oxidation state route employing W(CO)6 (Scheme 2). Starting from WCl6, the tungsten neopentylidyne complex [Me3CC:W{OCMe(CF3)2}3 (dme)] (1) can be synthesized as a key intermediate in four steps (11). However, this route requires the delicate use of six equivalents of neopentyl magnesium chloride, three of which are subsequently sacrificed by treatment with HCl. Alternatively, the preparation of the corresponding tungsten benzylidyne complex [PhC: W{OCMe(CF3)2}3(dme)] (3) can be achieved with better atom economy by reaction of W(CO)6 with phenyl lithium, followed by decarbonylation, oxidation with bromine and introduction of the hexafluoro-tert-butoxide ligands (12, 13). Finally, the reaction of 1 and 3 with the lithium reagent ImtBuNLi, which can be obtained from 1,3-di-tert-butylimidazolin- 2-imine (ImtBuNH) and methyl lithium (MeLi), furnishes the alkylidyne complexes 2 and 4 in high yields (14, 15). Both complexes should be equally active in catalytic alkyne metathesis, since the alkylidyne moiety is lost during the initiation step.

CATALYTIC REACTIONS AND THEORETICAL CALCULATIONS

In order to test the catalysts for preparative alkyne metathesis, the homodimerization of 1-phenylpropyne in the presence of 2

Figure 2. Design strategy for alkyne metathesis catalysts.

Scheme 2. Synthesis of catalysts 2 and 4, structures of catalysts 5 and 6.

Figure 3. Metathesis of 1-phenylpropyne using catalysts 2, 5 and 6.

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METATHESIS

This “bottom” approach affords a square-pyramidal metallacyclobutadiene with the alkylidene carbon atom in the apical position and a trans-orientation of the two alkoxides (see Figure in Table 1). These theoretical predictions could be confirmed by structural characterization of the metallacyclic product [(C3Et3)W(NImtBu){OCMe(CF3)2}3], obtained from the reaction of 2 with an excess of 3-hexyne (14).

The following conclusions can be drawn based on data in Table 1:1. In agreement with the experimental results, a significantly

higher barrier is calculated for the classical [Me3CC:W (OCMe3)3] system in comparison with 2 (∆G≠

298 = 32.92 kcal·mol-1 versus ∆G≠

298 = 26.05 kcal·mol-1, entries 1 and 3).2. The introduction of electron-withdrawing ligands such as

hexafluoro-tert-butoxide groups is clearly beneficial for achieving high catalytic activities as indicated by comparison with the corresponding tert-butoxide complex (∆G≠

298 = 33.84 kcal·mol-1 versus ∆G≠298 = 26.05 kcal·mol-1,

entries 2 and 3).3. Substitution of ImtBuN by ImDippN affords a significant

increase of the activation barrier and consequently a decrease of catalytic activity (∆G≠

298 = 26.05 kcal·mol-1 versus ∆G≠

298 = 37.55 kcal·mol-1, entries 3 and 4). 4. In agreement with the relative catalytic performance, the

calculated barrier for the amido N(tBu)Ar complex (Ar = 3,5-dimethylphenyl) adopts an intermediate position between those determined for the ImtBuN and ImDippN systems (∆G≠

298 = 31.22 kcal·mol-1, entry 5).

Furthermore, the theoretical calculations allow the following predictions:1. Substitution of ImtBuN in 2 by sterically less hindered ImMeN

should hardly change the catalytic activity, since the calculated activation barrier does not decrease significantly (∆G≠

298 = 26.05 kcal·mol-1 versus ∆G≠298 = 25.03 kcal·mol-1,

entries 2 and 6).2. Phosphoraneiminato ligands R3PN should be promising

ancillary ligands for designing efficient alkyne metathesis catalysts, since the activation barrier is lowered by substitution of ImtBuN in 2 for Me3PN (∆G≠

298 = 26.05 kcal·mol-1 versus ∆G≠

298 = 24.66 kcal·mol-1, entries 2 and 7). 3. Int roduct ion of b i s ( t r i f luoromethy l )benzy lox ide,

OCPh(CF3)2, or nonafluoro-tert-butoxide, OC(CF3)3, affords lower activation barriers (∆G≠

298 = 24.00 kcal·mol-1

contain the 1,3-bis(2,6-diisopropylphenyl)imidazolin-2-iminato (ImDippN) or the Ar(tBu)N (Ar = 3,5-dimethylphenyl) amido ligand, respectively (Scheme 2). The catalytic activit ies of these two complexes are clearly inferior, although the amido complex 6 performs satisfactorily at elevated temperature (80° C). To explain the differences of the experimentally observed catalytic activit ies and to uncover suitable structures for future optimization of our catalyst system, we have performed theoretical calculations using density functional theory (DFT). The symmetric metathesis of 2-butyne (MeC:CMe) was chosen as the model reaction (14, 15), and based on the conventional [2+2]-cycloaddition-cycloreversion mechanism, the first three relevant stationary points – catalyst plus 2-butyne, transition state (TS) and metallacyclobutadiene intermediate (IN) – of the rate-determining step were characterized for each of the nine selected catalysts (Table 1). It is interesting to note that, in contrast to calculations on d0-olefin metathesis catalysts (16), our results suggest that the incoming alkyne is approaching the tetrahedral alkylidyne complex through the triangular face, which is opposite to the imidazolin-2-iminato ligand.

Table 1. Relative B3LYP energies in kcal mol-1 for the reaction of selected catalysts with 2-butyne.a) Figure 4. Ring-closing metathesis reactions using catalyst 2.

To date only a limited number of species are known to

catalyze alkyne metathesis reactions efficiently, despite the

high potential for the application of alkyne metathesis

in areas such as organic synthesis, pharmaceuticals and

materials science

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REFERENCES AND NOTES

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2. T.J. Katz, J. McGinnis, J. Am. Chem. Soc., 97, pp. 1592-1594 (1975).3. For reviews on alkyne metathesis, see: (a) W. Zhang, J.S. Moore,

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8. (a) R.R. Schrock, D.N. Clark et al., Organometallics, 1, pp. 1645–1651 (1982); (b) J.H. Wengrovius, J. Sancho et al., J. Am. Chem. Soc., 103, pp. 3932–3934 (1981).

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and ∆G≠298 = 19.47 kcal·mol-1,

entries 8 and 9), indicating that these species could have high activities in catalytic alkyne metathesis reactions.

In addition to alkyne cross metathesis, we have also investigated ring-closing metathesis using catalytic amounts of 2 (Figure 4). Ring-closing metathesis of 6,15-dioxaeicosa-2,18-diyne employing two mol% of 2 under similar conditions as described above produced 5,14-dioxacyclohexadecyne within 120 min in 95 percent yield (14). We also studied the activity of our catalyst towards cyclization of other diynes such as o-, m- and p-bis-(3-pentynyloxymethyl)benzenes (17). Surprisingly, different reaction pathways depending on the substitution pattern of the substrates were observed: The m- and p-diynes selectively form the [10]metacyclophane or the [10.10]paracyclophane, respectively, whereas a mixture of monomeric and dimeric cycloalkynes is obtained in the case of the o-diyne. Again, theoretical calculations using DFT methods were employed to explain the different selectivities (17). In analogy to olefin metathesis (18), we supposed that catalyst 2 is able to establish an equilibium between monomeric and dimeric products by reversible r ing-opening and r ing-clos ing metathesis (RORCM) reactions. Accordingly, the relative standard Gibbs free energies ∆Go of the [10]- or [10.10]cyclophanes should dictate the product ratios, and in fact, an excellent agreement between the experimental and theoretical results was observed (17).

CONCLUSION AND PERSPECTIVE

Drawing on a new design concept, novel tungsten-based alkyne metathesis catalysts have been developed and successfully prepared by following different high and low oxidation state routes. In analogy to Schrock type olefin metathesis catalysts, excellent catalytic performance seems to rely on the combination of an electron-donating imidazolin-2-iminato ligand with electron-withdrawing alkoxides – it’s a game of give and take. The prototypical catalyst 2 exhibits high activity in alkyne cross metathesis and ring-closing alkyne metathesis reactions even at room temperature. So far, variation of the ligands in 2 afforded complexes with decreased catalytic activities, and these differences could be rationalized by comparative theoretical DFT studies. However, these calculations should also allow to reliably predict the catalytic performance of future catalyst systems and to uncover even more active species. Thus, a rational design of highly active alkyne metathesis catalysts seems to be possible through variation and optimization of the underlying push-pull situation. Furthermore, DFT calculations were also able to successfully predict the distribution of different products occurring in ring-closing metathesis reactions. The catalytic activitiy of 4, which is the benzylidyne analogue of 2, is currently investigated in our laboratory; initial results show that apart from sometimes slightly different induction periods, the catalytic performances of 2 and 4 are identical. New substrates and other types of alkyne metathesis reactions are also under exploration. Finally, it should be noted that the design concept for tungsten alkylidyne complexes can be fully transferred to the corresponding molybdenum-based catalysts, and recent results indicate that these systems are also highly promising candidates for applications in alkyne metathesis and should provide a new playground for chemists working in this exciting realm of homogeneous catalysis.

METATHESIS

New strategies for a rational catalyst design are still required in order to boost the recognition of

alkyne metathesis and to overcome the prevalence of olefin metathesis