Amidate Complexes of Tantalum and Niobium for the

Research Article pubs.acs.org/acscatalysis

Amidate Complexes of Tantalum and Niobium for the Hydroaminoalkylation of Unactivated Alkenes Jean Michel Lauzon, Patrick Eisenberger, Sorin-Claudiu Roşca, and Laurel L. Schafer* Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia, Canada V6T 1Z1 S Supporting Information *

ABSTRACT: A series of mono(amidate) Ta and Nb complexes with varying steric and electronic properties were synthesized. These complexes were screened as precatalysts for the hydroaminoalkylation of alkenes with secondary amines. Sterically demanding mono(amidate) Ta complexes were determined to be the most effective precatalysts. Isotopic labeling and kinetic studies were undertaken in an effort to elucidate the mechanism. The reaction was shown to be dependent upon catalyst and alkene concentration while being zero order in amine concentration. Mechanistic probes for radical species support a two-electron mechanism. Bis(amidate) species of Ta and Nb were also synthesized, with metallaaziridine formation observed for both metals. Insertion of acetonitrile into the reactive M−C bond yielded a representative five-membered metallacycle. Off-cycle equilibria and catalyst dormant states have been identified as areas for future catalyst development efforts. KEYWORDS: hydroaminoalkylation, tantalum, niobium, metallaaziridine, amidates, amine synthesis, kinetics

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INTRODUCTION Selective catalytic processes for the rapid synthesis of Ncontaining small molecules are the subject of intense current academic and industrial research.1 Specifically, the catalytic αalkylation of amines, or hydroaminoalkylation, via C(sp3)−H bond activation α to N and subsequent C−C bond formation has recently emerged as a promising tool for the synthesis of selectively substituted amines (Scheme 1).2,3 This process is

hydroaminoalkylation. Specifically, Sc(III) is useful for hydroaminoalkylation with 3° amines.4 Ti (IV) and Zr(IV) complexes have demonstrated potential for intramolecular αalkylation of 1° amines5,6 and intra- and intermolecular αalkylation of 2° amines with alkenes.5b,c,7−9 Furthermore, inspired by the pioneering studies of Clerici and Maspero10 and later Nugent and co-workers,11 Herzon and Hartwig conducted a detailed study using Ta(V) amido complexes as catalysts to promote hydroaminoalkylation, resulting in a broadened substrate scope and a more efficient catalytic system.12,13 Using deuterium labeling experiments,12 a mechanism (Scheme 2) has been proposed for such group 5 catalysts. During the course of previous investigations, an extensive screen of commonly used ancillary ligand motifs combined with Ta(NMe2)5 did not provide an efficient catalyst formulation.14 Notably, trends in auxiliary ligand design to promote desirable reactivity have not yet been established and features required to promote effective catalysis remain ill-understood for this transformation. To address these limitations, a number of Ta amidate complexes with the composition TaV(amidate)n(amido)5−n (n = 1, 2) have been identified as promising precatalysts, including enantioselective reactions.15,16 Hultzsch reported the use of axially chiral, silylated binaphtholate group 5 complexes as precatalysts for hydroaminoalkylation with ee values as high as 98%.17 Amidates as ancillary ligands have proved promising in supporting a number

Scheme 1. α-Alkylation of Amines: Formal Addition of an C(sp3)−H Bond α to N across a CC Double Bond

comprised of the formal addition of an C(sp3)−H bond α to an amine across a CC bond, resulting in the α-alkylation of amines. This process offers access to N-containing molecules with 100% atom economy and the use of common olefinic feed stock chemicals and unprotected amines. Notably this method avoids the use of stoichiometric coreagents (bases, oxidants) or additive cocatalysts or photocatalysts. However, this reaction demands a high degree of chemo-, regio-, and stereocontrol for it to become a valuable and reliable tool for synthesis. Thus, we have identified this little explored transformation as a desirable target for effort in catalyst development.2 To this end, several early-transition-metal complexes based on group 3−5 elements have been identified to catalyze © XXXX American Chemical Society

Received: April 21, 2017 Revised: June 28, 2017

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DOI: 10.1021/acscatal.7b01293 ACS Catal. 2017, 7, 5921−5931

Research Article

ACS Catalysis Scheme 2. Proposed Mechanism for Hydroaminoalkylation Using a Group 5 Metal Catalyst

Scheme 3. Synthesis of Nb- and Ta(amidate)(tetrakisdimethylamido) Complexes 1−6 via Protonolysis

hexanes at −30 °C. In the absence of air and moisture these materials are stable at ambient temperature, and after several months, no change in appearance and spectroscopic behavior is observed. The synthetic accessibility of a large variety of group 5 mono(amidate) complexes allows for the systematic exploration of reactivity. For group 5, the steric congestion about the metal center with four amido ligands, in addition to the amidate ligand, rationalizes the ease of formation and isolation of group 5 mono(amidate) systems. The reaction of N-(2,6-diisopropylphenyl)pivalamide with Ta- or Nb(NMe2)5 results in the clean formation of isostructural mono(amidate) complexes 115 and 2 (Figure 1).

of mono- and dinuclear complexes of catalytically competent high-oxidation-state early-transition-metal centers.18 Specifically, bis(amidate) complexes of Ti(IV) and Zr(IV) have been shown to efficiently catalyze the intermolecular hydroamination19,20 of alkynes and allenes and more recently the corresponding intramolecular hydroaminoalkylation reaction.5 In the coordination sphere of such transition metals, amidate ligands can adopt a number of bonding motifs ranging from chelating to bidentate (κ2-N,O), monodentate (κ1-O or -N), and bridging (μ-amidate).17,21,22 More recently, related Ta complexes have been prepared that exhibit increased enantioselectivity for select substrates.15,16,23 Notably, piperidine and protected alcohols have only been reported as substrates for our Ta amidate catalytic systems,14 demonstrating the ability of group 5 mono(amidate) precatalysts to perform challenging transformations. Here we report mechanistic insights to guide efforts in catalyst development. A series of group 5 amidate amido complexes have been prepared and characterized, and their activity as catalysts for hydroaminoalkylation and their behavior in stoichiometric reactions has been explored. Favorable ligand steric properties that exhibit enhanced reactivity have been identified. The solution-phase behavior of select complexes offers the opportunity to probe the hemilability of amidate ligands. Preliminary reaction kinetics, including labeling studies, are presented.

Figure 1. ORTEP representation of 2 drawn with 50% probability thermal ellipsoids. Hydrogen atoms are omitted for clarity. Metrical data for 1 and 2 are presented for comparison.15 Select bond lengths (Å) and angles (deg): 1, Ta−O1 2.099(3), Ta−N1 2.447(3), O1− Ta−N1 56.90(10), ∑∠(N3) 360; 2, Nb−O1 2.1133(8), Nb−N1 2.4651(9), O1−Nb−N1 56.59(3), N3−Nb−N5 101.06(4), ∑∠(N5) 360.

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RESULTS AND DISCUSSION Synthesis and Characterization of Group 5 Monoamidate Complexes. Early-transition-metal amidate complexes are synthesized efficiently using a protonolysis approach, in which a metal amido moiety is converted to a metal amidate species with concomitant neutral amine elimination.17 The reaction of equimolar amounts of M(NMe2)5 (M = Nb,24 Ta) and a corresponding organic amide at ambient temperature under an inert atmosphere in hexanes results in the highyielding synthesis of mono(amidate) tetrakis(dimethylamido) complexes 1−6 (Scheme 3) These materials are highly crystalline and are easily purified by recrystallization from

The metrical parallels between 1 and 2 can be explained by the ionic radii of the Nb and Ta centers (Nb(V), 0.78 Å; Ta(V), 0.78 Å).25 Bond distances and angles for the amidate ligand motif are found to lie in the range typical for early-transitionmetal amidates.26,27 Both complexes exhibit short M−Oamidate and long M−Namidate bonds. The amido ligands exhibit planar nitrogen, with sums of bond angles close to 360°. The axial M− Namido bonds are longer (2.047(4) Å average) than those in the equatorial plane of the chelating atoms, with the amido pseudotrans to Oamidate (1.974(3) Å average) having a shorter M−N 5922


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little effect on the Ta−Namido contacts in the plane of the amidate chelate but does cause a change of the axial amido bonds. The complexes also show a propensity to adopt an idealized trigonal geometry, on the basis of the increasing Neq− Ta−Neq bond angle, as the steric demand of the amidate ligand decreases (Table 1). In the extreme case of the N-supermesityl benzamidate 5, a κ1-O coordination mode with a very short Ta−Oamidate bond distance of 2.0586(15) Å is observed. This is accompanied by a decreased Camidate−Namidate distance and an obtuse O−C−N bond angle (127.34(18)°) in comparison to the chelating amidates (113.5(2)° average). The large C−O−Ta bond angle of 152.33(12)° and the data presented above suggest that the amidate in 5 is best described as an κ1-O-coordinated iminoalkoxide ligand occupying an axial position. Furthermore, the 13C{1H} NMR data for the amidate carbonyl carbon in 5 (δC 160.3) support κ1-O coordination in solution (δC 167.3− 180.4 for κ2-N,O species). In contrast to altering the Namidate substituent, varying the moiety bound to the Camidate has little effect on the metrical parameters of these mono(amidate) complexes. Of particular note is the Camidate−Namidate−Cipso bond angle, which is within experimental error for complexes 1 and 6 (125.1(3) and 124.7(2)°, respectively). Catalytic Reactivity and Selectivity of Group 5 Amidate Amido Complexes in Hydroaminoalkylation. The homoleptic group 5 amido complexes used for early αalkylation studies were found to catalyze the reaction between terminal olefins and short-chain dialkyl amines, in modest yields (20:1 are observed by 1H NMR spectroscopy. For example, the hydroaminoalkylation product of N-methylbenzylamine and allylbenzene is observed as a single diastereomer in the solution phase (δH 4.88, doublet) and can be isolated after N-tosylation (product 8, Scheme 4).32 The exclusive diastereoselectivity arises from the insertion of allylbenzene into the tantalaaziridine Ta−C bond (Scheme 4, I) with the phenyl group on the opposite face of the intermediate metallacyclic product (Scheme 4, II), thereby minimizing steric interactions. Once the five-membered metallacycle intermediate is formed, the relative stereochemistry of the product is defined. By varying reaction conditions (including catalyst loading, temperature, and reaction time), some known challenging substrates, such as unactivated 1,2-disubstituted alkenes (Table 5924


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Scheme 4. Synthesis of syn-N,4-Dimethyl-N-(2-methyl-1,3-diphenylpropyl)benzenesulfonamide (8) and Catalytic Intermediate II That Gives Rise to the Observed Diastereoselectivity

3, entries 1 and 2) and heterocycles (entries 3 and 4), can undergo this reaction.33 To date, no other catalyst system has been reported that uses fully saturated heterocycles, such as piperidine, as substrates for hydroaminoalkylation (product 12). Importantly, amines bearing an N-(p-methoxyphenyl) moiety can be used as substrates (entries 5 and 6), giving access to 1° amines after oxidative deprotection. Similarly, alkenes that bear a terminal protected alcohol are also efficient substrates (product 14). Probing Mechanism in Ta Amidate Catalyzed Hydroaminoalkylation. In order to further expand the substrate scope and improve catalyst TOF and TONs, a deeper understanding of the reaction mechanism is required. To this end, both stoichiometric and kinetic investigations, including deuterium labeling studies, using precatalyst 1 have been carried out. During the course of these investigations, byproducts 15 and 16 were identified (Scheme 5). These byproducts arise from

Scheme 6. Proposed Mechanism for Tantalum Catalyzed Hydroaminoalkylation Including Reactions off the Catalytic Pathway

Scheme 5. Byproducts 15 and 16 Formed from the Hydroaminoalkylation of 1-Octene and Dimethylamine Liberated from the Precatalyst

substantial H incorporation into the methyl group of the labeled amine, indicating reversible tantalaaziridine formation at subcatalytic temperatures. In addition to the scrambling of isotopes at the methyl position, the integration of the signal corresponding to the ortho protons of the phenyl ring of aniline decreases slightly, showing that ortho metalation is a competing side reaction that also occurs at mild temperatures. These results are consistent with intermediate D undergoing reversible ortho metalation. To date, 1 has not demonstrated any catalytic reactivity at these lower temperatures. Despite the observed deuterium-scrambling consistent with ortho metalation, under the reaction conditions no productive hydroarylation of olefins has been observed. To this end, [D3]-N-methylaniline can be reacted with 1octene in the presence of group 5 precatalysts to yield the deuterated product 7-d (Scheme 7). When Ta(NMe2)5 is used as the precatalyst, only 45% of the deuterium label is retained α to N with 46% deuterium incorporation into the ortho positions.11 In contrast, when [Cl3Ta(NMePh)2]2 or silylated binaphtholate niobium complexes are employed, >90% of the methylene group remains labeled.13,17 These contrasting results suggest that reversible tantalaaziridine formation and ortho metalation are more facile in the homoleptic system, whereas [Cl3Ta(NMePh)2]2 has a strong preference for alkene insertion (pathway B) over reversible tantalaaziridine formation (pathway D). When the Ta amidate 1 is subjected to these catalytic reaction conditions, the deuterated product 7-d is isolated in excellent yield (93%) with 60% of the deuterium label

the hydroaminoalkylation of 1-octene with the dimethylamine liberated from the precatalyst upon transamination with the Nmethylaniline substrate. However, diagnostic signals cannot be distinguished by 1H NMR spectroscopy, due to overlap with 1octene and product 7. Over the course of catalytic hydroaminoalkylation with 1, byproduct 16 is produced in quantities large enough to be tosylated and isolated by chromatography.34 This byproduct formation impedes quantitative monitoring of alkene consumption as the reaction progresses, thereby limiting the possibility of a complete kinetic analysis. However, early research into transition-metal-catalyzed hydroaminoalkylation has used deuterium-labeled substrates to provide insight into reaction kinetics via isotope effects and labeling studies. These reports disclosed side reactions such as reversible tantalaaziridine formation (Scheme 6, D) and ortho metalation of an aryl substrate (E).11,12 To investigate amido ligand exchange in Ta amidate species (Scheme 6), 1 was exposed to excess [D3]-N-methylaniline in a Teflon-sealed NMR tube. Complex 1 eliminates dimethylamine, detectable by 1H NMR (δH 2.21), at room temperature over a 24 h period, suggesting that ligand exchange and/or tantalaaziridine formation is facile for these systems, even at room temperature. Gentle heating to 65 °C results in 5925


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ACS Catalysis Scheme 7. Comparison of Deuterium Incorporation or Retention in 7-d for Ta Catalysts

remaining in the methylene group α to N and 23% D incorporation observed in the ortho positions. These results confirm that tantalaaziridine formation is rapid and reversible for precatalyst 1. Comparison of the relative initial rates (up to 20% consumption of amine) of the reaction of 1-octene with [D3]- and [D4]-N-methylaniline and its unlabeled congener using 10 mol % of 1 revealed a small kinetic isotope effect (kH/ kD = 1.4(1) and 1.5(1), respectively). These small effects may arise from the extensive equilibria that we have shown to be prevalent in this system and further corroborate a mechanism where the tantalaaziridine formation is not involved in the turnover-limiting step.17 In addition to labeling experiments, a preliminary kinetic study using precatalyst 1, N-methylaniline, and 1-octene in [D8]toluene at 130 °C was performed in Teflon-cap-sealed NMR tubes with monitoring by 1H NMR spectroscopy using 1,3,5-trimethoxybenzene as an internal standard. First, under pseudo-first-order conditions (10-fold excess of 1-octene and 10 mol % of catalyst), a linear plot was observed for over 2 halflives (75% consumption) of N-methylaniline before a sharp decrease in rate (Figure S5 in the Supporting Information). This observation suggests a zero-order dependence on amine concentration and contrasts with other catalysts that display a first-order dependence in amine.17 Next, the reaction was carried out with various catalyst loadings (1, 1.5, 2, 2.5, 3, 4, 5, and 7.5 mol %, 4.3−32.2 mM), using a 1:1.5 ratio of N-methylaniline to 1-octene in a constant volume of [D8]-toluene, while the consumption of Nmethylaniline was monitored. Figure 3 shows a linear behavior vs reaction time, consistent with the reaction being zero order in amine. However, when the observed initial rates derived from the linear models are plotted as a function of catalyst concentration, two different regimes are observed over the concentration range (Figure S6b in the Supporting Information). Analysis of the data obtained with up to 5 mol % catalyst loading revealed a linear correlation, suggesting first-order behavior.17 However, increasing the loading above this threshold, up to 20 mol % (85.9 mM), does not increase the rate of reaction, indicative of the formation of dormant states and/or unfavorable equilibria off the catalytic cycle. These species are proposed to be inactive multimetallic species, as recently proposed for the homoleptic titanium catalyst Ti(NMe2)4.5d With 1, it is proposed that these catalytically inactive species are formed at catalyst loadings above 5 mol %. To confirm this hypothesis, a series of five catalytic reactions was performed

Figure 3. Consumption of amine as a function of time for the hydroaminoalkylation of N-methylaniline with 1-octene catalyzed by varying concentrations of 1.

with the relative molar ratios of N-methylaniline, 1-octene, and 1 (1:1.5:0.05) held constant while the absolute concentration of the reaction mixtures in 0.5 mL of [D8]-toluene was varied. Interestingly, the initial rates (up to 30% amine consumption) were found to be indistinguishable for all concentrations measured (2, 1, 0.5, 0.25, and 0.125 M in amine) within 2 standard deviations. This suggests that increases in catalyst concentration relative to the substrates, rather than the absolute concentration of the catalytic species present in the reaction mixture, are the determining factors for the formation of offcycle catalytic species. Regrettably, pseudo-first-order conditions could not be employed for elucidation of the alkene reaction order. The large excess of N-methylaniline causes an overlap in substrate and product signals (δH 6.40 and 6.48, respectively), making quantitative analysis impossible. Alternatively, in attempts to employ initial rate methods, monitoring of alkene consumption is complicated by the formation of byproducts 15 and 16 and is thus unreliable. Therefore, in order to probe reaction order in alkene, a series of experiments was conducted in which the initial concentration of alkene was varied while catalyst loading, amine concentration, and reaction volume were held constant. Under these conditions, a positive, linear relationship between both the initial rate of consumption of N-methylaniline and the initial rate of formation of 7 was observed. Though byproduct formation continues to plague the quantitative analysis of this data, as noted by the different rates of substrate consumption and product formation (Table 4), it can be stated that the rate of hydroaminoalkylation catalyzed by mono(amidate) 1 is dependent on the initial concentration of alkene. These combined preliminary kinetic data suggest an empirical rate law at low catalyst loadings that is zero order in amine, is first order in catalyst, and has a nonzero dependence on alkene concentration. Labeling experiments have demonstrated that the turnover-limiting step does not involve tantalaaziridine formation and that ortho metalation is a competing nonproductive side reaction. To date, the possibility of a mechanism for the hydroaminoalkylation with early transition metals involving oneelectron radical processes has not been explored in the 5926


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ACS Catalysis Table 4. Initial Rate of Consumption of N-Methylaniline and Initial Rate of Formation of 7 as a Function of Initial Alkene Concentration c(t0)alkene (M)

rate of N-methylaniline consumption (M h−1)

rate of formation of 7 (M h−1)

0.25 0.50 0.75 1.00

0.045(5) 0.070(5) 0.090(3) 0.127(2)

0.043(2) 0.067(3) 0.090(6) 0.106(9)

(amidate) complexes were synthesized. Indeed, these complexes were found to be catalytically competent (vide infra) but significantly less reactive than their mono(amidate) counterparts. This decrease in catalytic efficiency suggests that bis(amidate) complexes could be used as model systems to characterize products relevant to catalytic intermediates. To this end, the reaction of 2 equiv of N-phenylpivalamide and Ta(NMe 2 ) 5 formed tantalum(V) bis(amidate)tris(dimethylamido) complex 18 (Scheme 9). This complex Scheme 9. Synthesis of 18 and ORTEP Representation of the Solid-State Molecular Structure Drawn with 50% Probability Thermal Ellipsoidsa

literature. However, the redox couple is accessible between d0 Ta(V) and d1 Ta(IV) and has been reported to occur between 0.31 and 0.74 V in traditional organic solvents.35 Synthetically, Ta(V) centers can be efficiently reduced to d1 species with nucleophilic reagents such as n-butyllithium.36 On the basis of this ease of reduction, the possibility of radical participation from a Ta(IV) center during catalysis is plausible and should be considered. In our work, the absence of ambient light, which can initiate radical processes, does not affect the rate of hydroaminoalkylation catalyzed by mono(amidate) tantalum complexes. Furthermore, a cyclopropyl moiety was built into an alkene substrate (17) in order to probe the possibility of one-electron processes in hydroaminoalkylation. The radically induced ring opening of cyclopropyl rings has been used extensively to study radical mechanisms in a variety of systems.37 Assuming a radical process for the insertion of the alkene into the Ta−C bond of the tantalaaziridine, instead of the expected hydroaminoalkylation product, a ring-opened alkene containing linear αalkylation product could be formed. When the hydroaminoalkylation of N-methylaniline with substrate 17 was performed under catalytic conditions (Scheme 8), complete consumption of the cyclopropyl-containing alkene Scheme 8. Hydroaminoalkylation of N-Methylaniline with Substrate 17

a

Hydrogen atoms are omitted for clarity. Select bond lengths (Å) and angles (deg): Ta1−N1 2.2746(15), Ta1−O1 2.1510(12), Ta1−O2 2.0035(12), Ta1−N3 1.9602(16), Ta1−N4 1.9698(17), Ta1−N5 1.9872(16), N1−C1 1.300(2), C1−O1 1.289(2), O2−C12 1.317(2), C12−N2 1.273(2); N1−Ta1−O1 58.27(5), N1−C1−O1 112.89(15), O2−C12−N2 125.81(15).

was observed after 24 h. On the basis of the 1H NMR spectrum the cyclopropyl ring remained intact even after the alkene substrate was consumed. The four distinct signals were shifted slightly upfield to δH 0.62, 0.72, 1.37, and 1.53, respectively, and retained the diagnostic coupling patterns associated with cyclopropyl moieties. Additionally, whereas 17 has three distinct multiplets (δH 4.88, 5.02, 5.35) assignable to alkene protons, there were no signals in the region between 3.5 and 6.0 ppm, suggesting no alkene functionality in the product. This result suggests that hydroaminoalkylation catalyzed by tantalum amidate complexes proceeds via a two-electron mechanism as previously postulated (Scheme 2). Synthesis and Characterization of Model Systems for Catalysis. In an effort to investigate the mechanistic proposal in Scheme 2, attempts to isolate catalytic intermediates were carried out using mono(amidate) complex 1. Unfortunately, none of the target compounds (Scheme 2A−C) could be identified while the catalytic reaction was monitored by NMR spectroscopy. In an effort to isolate intermediates by using less reactive complexes,15 more sterically bulky group 5 bis-

exhibits a pseudo-trigonal-bipyramidal coordination geometry about Ta, with one amidate ligand coordinated in a κ1-O fashion and the other κ2-N,O. Notably, the monodentate κ1-Obound amidate fragment shows considerable CN doublebond character (C12−N2 1.273(2) Å) and an obtuse bond angle (O2−C12−N2 125.81(15)°) in comparison to the chelating amidate ligand (N1−C1 1.300(2) Å, N1−C1−O1 112.89(15)°). In solution at ambient temperature, a species consistent with the solid-state coordination mode is observed by NMR spectroscopy. Two different amidate environments, monodentate (κ1-O) and chelating, bidentate (κ2-N,O), are observed with carbonyl resonances at δC 168.1 and 184.5, respectively. Two broad, overlapping methyl amido resonances are observed in both 1H and 13C{1H} NMR spectra (δH 3.42 and 2.84, δC 45.2 and 48.7), consistent with two equatorial and one axial amido ligand slowly exchanging on the NMR time scale. At low temperature (T = −81 °C) these broad resonances start to sharpen and eventually six distinct (although broad) signals for 5927


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with simultaneous release of dimethylamine. New signals at δH 1.03 and 1.11 accompany the dimethylamine signal, suggestive of two additional tBu environments other than the broad signal attributed to 18 (δH 1.27, T = 101 °C). Additional signals at δH 2.16 an 2.26 and at δH 3.22, 3.35, and 3.38 can be assigned as the diastereotopic Ta−CH2 protons and amido-N−CH3 environments generated during tantalaaziridine formation, respectively.14 When a constant temperature of 101 °C is maintained, numerous amido and tBu CH3 signals emerge that cannot be assigned to 18 or the corresponding tantalaaziridine. These signals persist even after the sample has been cooled to room temperature, suggesting that new species are being formed that are not in equilibrium with complex 18. Such undefined species may be dormant multimetallic Ta complexes. In an effort to hinder these dynamic processes, steric bulk could be added to the ortho positions of the amidate N substituent. To this end, the reaction of Ta(NMe2)5 and 2 equiv of N-(2,6-dimethylphenyl)pivalamide gave a product with magnetically inequivalent amidate ligand resonances (Scheme 11). In this case, in

each of the amido CH3 groups are observed. Figure 4 shows the aliphatic region (0.0−4.0 ppm) of the temperature-dependent

Scheme 11. Synthesis of Stable, Crystalline Nb and Ta Aziridines Supported by Two Amidate Ligands

Figure 4. Variable temperature (−80.9 to +101.3 °C) 400 MHz 1H NMR study of 18.

H NMR spectra of 18 from −81 to 101 °C, which reveals several dynamic processes occurring in the Ta coordination sphere. The dynamic processes observed in the cold regime, from −81 to −6 °C, are completely reversible and are unaffected by repeated cooling and warming of the sample within this range. At temperatures above 41 °C, the amido methyl signals coalesce, suggesting fast exchange on the NMR time scale. Further upfield, two distinct amidate ligand tBu signals also coalesce at elevated temperatures (73.3 °C), indicative of a dynamic exchange between the κ1-O and the κ2N,O binding modes (Scheme 10). At temperatures above 25 °C, a doublet corresponding to the methyl substituents of neutral dimethylamine appears at δH 2.21, presumably originating from tantalaaziridine formation 1

addition to the 2 equiv of HNMe2 stemming from the protonolysis by the amide proligands, an extra 1 equiv of HNMe2 was spontaneously eliminated, resulting in the formation of the isolable tantalaaziridine 19. Presumably, the increase in steric bulk at the ligand induces the spontaneous room-temperature elimination of neutral amine from the metal center. The spontaneous C−H bond activation α to N with concomitant amine elimination to yield tantalaaziridine complexes has rarely been documented for d0 systems.6,8f,38 More commonly, mixed alkyl amido systems form metallaaziridines by alkane elimination.39 The resulting complex 19 can be isolated in excellent yield (84%) with analytically pure samples, suitable for single-crystal X-ray analysis.15 The solidstate molecular structure of 19 has been previously reported. In the solution phase the signals corresponding to the diastereotopic protons of the metallaaziridine moieties resonate at δH 2.34 and 2.49 (2JH,H = 3.5 Hz) and δC 59.1 for 19. Interestingly, the amidate bite angles in the mono(amidate) complexes (56.9−57.7°) tend to be slightly more acute in comparison to the bis(amidate) 19 (59.3°). By replacement of Ta(NMe2)5 with the lighter, homologous, homoleptic Nb(NMe2)524 complex the corresponding niobaaziridine 20 could be prepared in quantitative yield. Complex 20 crystallizes in the P21/n space group and exhibits a coordination geometry similar to that of its tantalum analogue 19, as depicted in Figure 5. The two amidate ligands are bound to the metal in a κ2-N,O fashion displaying identical tight bite angles (59°), as found for 19.

Scheme 10. Proposed Equilibrium between Coordination Modes of 18 Illustrating the Dynamic Exchange of Amidate Binding Modes Observed on the NMR Time Scalea

a

Amidate N and O atoms are labeled for illustrative purposes. 5928


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products. However, when complex 19 was reacted with acetonitrile in benzene at room temperature, the CN bond inserted into the Ta−C bond of the metallaaziridine creating a five-membered metallacycle that was ultimately observed as the isomerized product 21 (Scheme 12). Such isomerizations have been previously observed for nitrile insertions into earlytransition-metal−carbon bonds.42 Complex 21 can be isolated as a blood red powder that can be recrystallized from refluxing hexanes to give single crystals suitable for X-ray diffraction. The molecular structure of 21 is shown in Figure 6. The solitary olefinic proton of the metallacycle 21 (δH 5.86 ppm) serves as an informative, diagnostic spectroscopic handle.

Figure 5. ORTEP representation of the solid-state molecular structure drawn with 50% probability thermal ellipsoids of 20. Hydrogen atoms are omitted for clarity. Select bond lengths (Å) and angles (deg): Nb− O1 2.146(4), Nb−N1 1.968(5), Nb−N2 1.926(5), Nb−C1 2.204(6); O1−Nb−N4 59.05(15), C1−Nb−N2 39.5(2), ∑∠(N1) 360, ∑∠(N2) 360.

In the solution phase the formation of metallaaziridine is confirmed by NMR spectroscopy with δH 2.42 and 2.50 (2JH,H = 5.6 Hz) and δC 54.4 for 20 comparing favorably with the data for 19 listed above. These values are in the typical range of known pentavalent group 5 metallaaziridine complexes and are notably different from those observed for the related η2-imine complexes with typical values for δC being >200 ppm.40 While the less bulky complex 18 displays mono- and bidentate binding modes at ambient temperature in both solution and solid phases, at elevated temperatures metallaaziridine formation can be induced. We propose that the hemilabile nature of the amidate ligand allows for coordinationsite variability about the metal center and with suitable steric bulk, as in 19 and 20, can serve to stabilize the typically reactive metallaaziridine moiety as an isolable material. Ligand participation in the H-abstraction mechanism cannot be excluded, considering that hemilabile ligands, such as carboxylates, have been shown to actively participate in C−H activation mechanisms via concerted metalation−deprotonation.41 It has been well documented that tantalaaziridines react with unsaturated fragments such as alkenes, carbonyls, nitriles, and isocyanides in a stoichiometric fashion to give the corresponding organic insertion products after workup.40 Surprisingly, exposing 19 to various alkenes, internal alkynes, and conjugated ketones results in no reaction, even at temperatures of 90 °C. In comparison, reactions with terminal alkynes, acetophenone, benzaldehyde, and phenyl isocyanate yield complex mixtures of

Figure 6. ORTEP representation of the single-crystal X-ray structure of product 21 drawn with 50% probability thermal ellipsoids. Most hydrogen atoms are omitted for clarity. Select bond lengths (Å) and angles (deg): Ta−N1 2.2974(15), Ta−O1 2.1376(13), Ta−N2 2.2223(15), Ta−O2 2.2078(13), Ta−N3 1.9946(16), Ta−N4 2.0623(16), Ta−N5 2.0428(16); N1−Ta−O1 58.56(5), N1−C1− O1 112.77(16), N2−Ta−O2 58.47(5), N2−C2−O2 112.40(16).

This complex can be viewed as a model of the five-membered metallacycle proposed in the catalytic cycle. The difficulty observed in inserting unsaturated molecules into the tantalaaziridine Ta−C bond corroborates the dependence of catalytic rate on alkene concentration. To investigate the effectiveness of bis(amidate) complexes as precatalysts for hydroaminoalkylation, complex 19 was screened in a manner similar to that for the aforementioned mono(amidates) (Table 2). Despite the fact that the proposed catalytically relevant metallaaziridine moiety was preinstalled, 19 displayed sluggish reactivity in comparison to precatalysts 1−5, achieving just 71% conversion even with increased temperatures (130 °C) and

Scheme 12. Insertion of Acetonitrile into Tantalaaziridine 19

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Research Article

ACS Catalysis Notes

longer reaction times (168 h). Notably, no spectroscopic signals consistent with loss of proteo ligand were observed. Thus, if we presume a similar mechanistic profile to the mono(amidate) precatalyst and consider the mechanistic data observed to date, the reduced reactivity may be attributed to sterically hindered alkene insertion.

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The authors gratefully acknowledge Boehringer Ingelheim (Canada) Ltd and the NSERC (Strategic Grants Program) for supporting this work. P.E. thanks the Swiss National Science Foundation for a PDF. J.M.L. thanks the NSERC for a CGS-D scholarship. This research was undertaken, in part, thanks to funding from the Canada Research Chairs program. Dr. Neal Yonson and Mr. Jacky Yim are also acknowledged for their assistance with X-ray structure determination.

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CONCLUSION A series of amides, varying in both steric and electronic properties, have been reacted with group 5 homoleptic dimethylamido starting materials to yield mono- and bis(amidate) complexes. Steric bulk on the Namidate substituent plays a determining role in how the amidate binds to the metal center, while changes in electronic properties evoke minimal variation. During the screening of mono(amidate) complexes 1−6 as precatalysts for hydroaminoalkylation, a positive correlation between steric bulk and reactivity was observed. The tantalum mono(amidate) 1, with isopropyl groups at the 2,6-aryl positions of the amidate, is a promising precatalyst for this reaction and has a broad substrate scope with excellent regio- and diastereoselectivity. The ability to use piperidine (12) and protected alcohols (14) as substrates has yet to be reported for any other system. Experiments involving deuterium-labeled substrates under catalytic conditions gave valuable information on how 1 behaves during catalysis, including off-cycle equilibria. Through reaction kinetics, a preliminary empirical rate law was elucidated which suggests that Ta mono(amidate) catalyzed hydroaminoalkylation is zero order in amine, is first order in catalyst, and exhibits a nonlinear dependence on alkene concentration. The bis(amidate) complexes were found to be less reactive catalysts but offer the opportunity to study models for reactive intermediates proposed in group 5 amidate hydroaminoalkylation catalysis. Complex 18 displays both monodentate (κ1-O) and chelating, bidentate (κ2-N,O) amidate ligands and demonstrates dynamic behavior over a broad temperature range. The bis(amidates) 19 and 20 are formed by the spontaneous elimination of an extra 1 equiv of dimethylamine and reveal stable metallaaziridine moieties which can be reacted with acetonitrile in the case of 19 to give a model system (21) of the five-membered metallacycle proposed in the catalytic cycle. These results offer a more in-depth look into fundamental ligand effects of group 5 amidate complexes on catalytic hydroaminoalkylation and provide key mechanistic insights to aid ongoing catalyst development efforts.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acscatal.7b01293. Detailed experimental information for reported compounds (including NMR spectra), catalytic reactions and products, kinetic investigations, and X-ray data (PDF) Crystallographic data (CIF)

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REFERENCES

AUTHOR INFORMATION

Corresponding Author

*E-mail for L.L.S.: [email protected]. ORCID

Laurel L. Schafer: 0000-0003-0354-2377 5930


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ACS Catalysis

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Amidate Complexes of Tantalum and Niobium for the

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