Enantioenriched Molybdenum Dearomatization: Dissociative

Mar 8, 2018 - Enantioenriched Molybdenum Dearomatization: Dissociative Substitution with Configurational Stability. Philip J. Shivokevich , Jeffery T...
0 downloads 0 Views 3MB Size
Download PDF
Article Cite This: Organometallics XXXX, XXX, XXX−XXX

Enantioenriched Molybdenum Dearomatization: Dissociative Substitution with Configurational Stability Philip J. Shivokevich,† Jeffery T. Myers,† Jacob A. Smith, Jared A. Pienkos, Steven J. Dakermanji, Emmit K. Pert, Kevin D. Welch, Carl O. Trindle, and W. Dean Harman* Department of Chemistry, University of Virginia, Charlottesville, Virginia 22904, United States S Supporting Information *

ABSTRACT: The preparation and properties of the complex (RMo,R)MoTp(NO)(DMAP)(η2-α-pinene) are described (∼10 g scale; DMAP = 4-(dimethylamino)pyridine; Tp = hydridotris(pyrazolyl)borate). This complex undergoes exchange of the pinene with a wide range of other π ligands including acetone, ethyl acetate, N,N-dimethylformamide, acetonitrile, and naphthalene. Treatment of the α-pinene complex with iodine results in the complex (S)-MoTp(NO)(DMAP)(I), which is recovered in enantioenriched form (er = 99:1; yield >90%; scale 4.6 g). Reduction of this molybdenum(I) precursor results in enantioenriched molybdenum(0) complexes, including (R)-MoTp(NO)(DMAP)(η2-trifluorotoluene). Sequential treatment of this arene complex with acid, a masked enolate, and iodine regenerates MoTp(NO)(DMAP)(I) along with an alkylated 1-(trifluoromethyl)cyclohexa-1,3-diene with an er value as high as 99:1. This process demonstrates the efficient transfer of asymmetry from α-pinene to the diene product. Accompanying studies with (1R)-myrtenal reveal a redox-catalyzed pinene/myrtenal ligand exchange occurring through Mo(I) intermediates.

■

INTRODUCTION Chiral at metal organometallic complexes such as [MnCp(CO)(NO)(PPh3)]+,1 where the only asymmetric element is the geometric arrangement of four or more different ligands around the metal, have fascinated chemists for decades. Brunner’s report describing the resolution of this complex set the stage for the pioneering work of Faller,2 Gladysz,3 Davies,4 Liebeskind,5 and others,6 who were interested in the relevance of metal stereocenters to asymmetric synthesis of organic compounds.7 The ability to prepare resolved forms of such complexes and understand the factors that provide their configurational stability are vital to the design of new or more efficient catalytic systems. Configurational stability is especially challenging when a process involves dissociation of a ligand. For over two decades, Gladysz and co-workers comprehensively investigated the chiral recognition and configurational stability of the Lewis acid [ReCp(NO)(PPh3)]+,3 including substitution reactions that retained the rhenium stereocenter. More recently, a chiral-atmetal Ir(III) complex, prepared from achiral ligands, was also shown to undergo substitution with retention.8 Our own interest in this field arises from our program in η2-coordinate activation of aromatic molecules. Transition metals typically form complexes with arenes in which all six carbons of the ring are coordinated (η6).9 However, complexes with lower hapticities are also known (e.g., η4, η2), and in all cases, the reactivity of the arene is enhanced. Specifically, chiral π-basic complexes of the type {MTpL1L2} (where M = Re, W, Mo; Tp = hydridotris(pyrazolyl)borate) are capable of forming η2-coordinated adducts with © XXXX American Chemical Society

arenes that can undergo electrophile-initiated organic reactions.10−18 Through a combination of chiral recognition in the coordination event and stereoelectronic differentiation in the reaction with the electrophile, the chirality of the metal stereocenter is translated to the organic substrate (Scheme 1). The stereochemistry of subsequent reactions is also guided by the position of the metal. These stereochemical features, along with good regiocontrol, can lead to selective formation of products with multiple stereocenters derived from the aromatic ring (Scheme 2).14−18 The most attractive feature of the synthetic approach outlined in Scheme 1 is the potential to prepare organic products from any aromatic ligand using the same global, optically active precursor, such as compound 1 or 2 in Scheme 2. Our approach to obtaining these enantioenriched aromatic systems has been to prepare and separate diastereomer precursors with chiral alkene derivatives15 or chiral acids.18 In order for this approach to be general, substitution reactions, such as those shown in Scheme 2 must occur for any aromatic substrate with complete retention of the configuration of the metal. Fortuitously, in the case of {ReTp(CO)(MeIm)} (MeIm = N-methylimidazole)14,15 and {WTp(NO)(PMe3)},17−19 we have found this to be the case, Special Issue: Organometallic Complexes of Electrophilic Elements for Selective Synthesis Received: January 15, 2018

A

DOI: 10.1021/acs.organomet.8b00027 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics Scheme 1. Global Approach to Enantioselective Dearomatization

Scheme 2. Examples of Dearomatization Using Enantioenriched Tungsten or Rhenium Precursorsa

despite the fact that ligand substitution for these d6 systems has been shown to occur by a dissociative mechanism. Although the synthesis of a molybdenum-based η2-arene complex, MoTp(NO)(MeIm)(η2-naphthalene), was first reported by our laboratories over a decade ago,13 only recently have dearomatization reactions been systematically investigated for this metal.20,21 In this context, using molybdenum in place of a heavy metal offers several practical advantages. The naphthalene complex MoTp(NO)(DMAP)(η2-naphthalene) (4) is readily formed from MoTp(NO)(DMAP)(I) (3), which can be prepared on a 150 g scale from Mo(CO)6 in three steps with an overall yield of 65% (DMAP = 4-(dimethylamino)pyridine). In addition to improvements in economy and scale, the oxidative removal of the organic product is more efficient for molybdenum. For example, as shown in Scheme 3, dihydronaphthalene compounds (6), derived from the naphthalene complex 4, can be liberated from the metal (5) with iodine, regenerating the molybdenum(I) complex 3 in 87% average yield.20 By a similar process, α,α,αtrifluorotoluene (TFT) can be bound (7), elaborated to a diene (8), and removed from the molybdenum (9), with good recovery of the molybdenum(I) precursor (3; 89%).22 Until now, organic products derived from the procedures in Scheme 3, such as 6 and 9, have been obtained only in racemic form. The following account describes some of the challenges and advances in developing an enantioenriched dearomatization process for this second-row transition metal.

a

Substitution reactions that form the aromatic complexes (blue) occur with configurational stability of the metal stereocenter.

Scheme 3. Molybdenum-Promoted Dearomatization of Naphthalene and Trifluorotoluene (a)

■

RESULTS AND DISCUSSION The terpene α-pinene is a sterically hindered alkene that is readily available as either enantiomer. Earlier work from our group demonstrated that racemic ReTp(CO)(MeIm)(η2-benzene) exchanges with (R)-α-pinene to form two diastereomers,15 differing in the

a

E.g., Nu = enolate, pyrrole.

configuration of the stereogenic metal center (Figure 1). These isomers have widely differing substitution characteristics:15 the “matched” isomer features the alkene methyl group of the pinene B

DOI: 10.1021/acs.organomet.8b00027 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics

on a large scale (11 g). Furthermore, when (RMo,R)-10 was generated via ligand exchange in THF from a racemic mixture of the trifluorotoluene analogue 7,22 the yield detected in solution was virtually quantitative (>90%, 1H NMR spectrum of solution aliquot in acetone-d6). Presumably, the lower yield reflects the inefficiency of the sodium reduction, which generates a highly reactive [MoTp(NO)(DMAP)(I)]− intermediate. This moderate yield has been observed with other complexes of the form MoTp(NO)(DMAP)(η2-L) prepared from Mo(I) precursors.20−22 While the high efficiency for this asymmetric transfer process23 was welcome news, it foreshadowed a weakness with the second-row metal system: the high yield and diastereoselectivity observed for the α-pinene complex required that the {MoTp(NO)(DMAP)} stereocenter epimerize (Scheme 4), and such an event could thwart the ability to prepare resolved complexes with aromatic molecules (vide supra). Attempts to elucidate the structure of 10 via crystallography were unsuccessful. However, the powerful π-acidic nature of the nitrosyl ligand in {MoTp(NO)(DMAP)} dictates that the CC bond of the pinene ligand in (RMo,R)-10 is oriented parallel to the Mo−DMAP bond axis.12,24 In this manner, the pinene π* orbital can overlap with the HOMO of the {MoTp(NO)(DMAP)} fragment, maximizing the back-bonding interaction. Thus, eight diastereomers (10A-H) are possible for the (R)-α-pinene complex, as shown in Figure 2. The bulky gem-dimethyl group of the

Figure 1. Observed diastereomers for ReTp(CO)(MeIm)(α-pinene). The “matched” isomer is thermodynamically favored and features a pinene methyl group in the Tp pocket (green).

oriented in a Tp pocket and is kinetically stable even at elevated temperatures. In contrast, the “mismatched” diastereomer is destabilized from the interaction of the same pinene methyl group with the pyrazole ring trans to the CO. In this case, the pinene readily undergoes displacement by other unsaturated hydrocarbons, with complete retention of the metal stereocenter (e.g., (S)-1).15 Given the similar topology between the {ReTp(CO)(MeIm)} and the {MoTp(NO)(DMAP)} systems, it seemed reasonable to explore the ability of α-pinene to resolve the latter complex. When the racemic Mo(I) precursor 3 is reduced with sodium in the presence of (R)-α-pinene (2.1 M), the complex (RMo,R)MoTp(NO)(DMAP)(η2-α-pinene) ((RMo,R)-10) was synthesized as a single stereoisomer in 43% isolated yield. As a solid, (RMo,R)-10 shows no decomposition after 30 days of storage at room temperature under nitrogen, making its synthesis practical Scheme 4. Asymmetric Transfer from (R)-α-Pinene to a Molybdenum Stereocenter of (RMo,R)-10

Figure 2. Quadrant perspective of the eight stereoisomers 10A−H for the (R)-α-pinene complex.

terpene effectively eliminates the possibility of coordination to one face of the alkene, and this feature reduces the number of possible diastereomers to four (A, B, E, F). Considering this, along with the assumption that the bulk of the bicyclic terpene would be near the unimposing nitrosyl group, we initially predicted that only 10A and F would be viable isomers, analogous to those observed for the rhenium system in Figure 1.15 For the complex ReTp(CO)(MeIm)(η2-propene), the steric strain between the methyl group of the propene and a pyrazole ring has been determined to be >9 kcal/mol,25 and apparently in 10F a similar C

DOI: 10.1021/acs.organomet.8b00027 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics

Scheme 5. Ligand Exchange Reactions for (R)-α-Pinene Complex (R,R)-10Aa

a

Figure 3. Quadrant perspective and calculated structures for the matched and mismatched isomers (RMo,R)-10A and (RMo,R)-10F.

Reaction conditions: benzene-d6; ∼2 M ligand, 48 h.

Table 1

steric interaction of the pinene methyl group (shown in red in Figures 2 and 3) renders this isomer too unstable to be isolated for the weaker π-base {MoTp(NO)(DMAP)}. The assigned stereochemistry of 10A (Figure 1) is supported by NOESY data and the unusual chemical shift (0.6 ppm) of the alkene methyl substituent, which comes about from its being nested between two pyrazole rings (Figure 3, shown in green).15 DFT calculations confirm the location of the methyl group in a Tp pocket for the matched isomer (10A; green highlight in Figure 3), and indicate that the mismatched isomer (10F) is 3.4 kcal/mol higher in energy. Calculations for other isomers in Figure 2 failed to converge. Ligand Exchange. In contrast to what was observed for rhenium15 or tungsten,17 the “matched” α-pinene isomer (RMo,R)-10A undergoes ligand exchange with a wide range of unsaturated ligands under ambient conditions (Scheme 5). Stirring a benzene-d6 solution of this complex with the desired ligand (Table 1) affords the corresponding product in moderate yields. Notable examples include η2-naphthalene (4), η2-acetone (11), η2-ethyl acetate (12), and η2-acetonitrile (13) complexes. These compounds show spectroscopic characteristics similar to those of their {MoTp(NO)(MeIm)} and {WTp(NO)(PMe3)} analogues.12,26,27 In addition, η2-coordinate complexes of DMF (14) and α,α,α-trifluorotoluene (7) were formed from the α-pinene complex (RMo,R)-10A, but were too labile to be isolated in pure form. While using deuterated solvents allowed us to readily collect rate data, in general we have found that complexes such as 11−16 (as well as the α-pinene complex 10A) are best prepared using the previously reported trifluorotoluene derivative 7 (Scheme 6).22 Half-lives were determined for many of the displacement reactions shown in Scheme 5, and these values are collected in Table 1. The deuterated ligands were used as the solvent where practical, and in other cases, a 0.1 M solution of the ligand in benzene-d6 was used. In most cases, half-lives were found to range from 10 to 15 h at 25 °C, regardless of the nature of the ligand or concentration (e.g., neat or as a 0.1 M benzene solution). This narrow range of half-lives provides strong support for a dissociative

L

compound

half-life deuterated solvent (h)

ΔG⧧(25 °C) (kcal/mol)

acetone (neat) acetone (0.1 M benzene-d6) naphthalene (0.1 M benzene-d6) ethyl acetate (0.1 M benzene-d6) acetonitrile (neat) DMF (neat)

11 11 4 12 13 14

10.3 16.3 15.6 15.5 11.5 15.0

23.9 24.2 24.1 24.1 24.0 24.1

ligand substitution mechanism, analogous to that observed with Os, Re, and W analogues.10−12,28,29 Assuming a two-step mechanism with pinene dissociation as the rate-determining step, the half-lives in Table 1 correspond to a free energy of activation for ligand dissociation of 24.0 ± 0.2 kcal/mol at 25 °C. Stereochemical Retention. With both ReTp(CO)(MeIm)(η2-α-pinene) and WTp(NO)(PMe3)(η2-α-pinene) systems, substitution of the pinene for another ligand takes place with retention of the stereogenic metal configuration. This indicates that the putative square-pyramidal intermediates in this process, {ReTp(CO)(MeIm)} and {WTp(NO)(PMe3)}, do not racemize during the substitution process. The stereochemical stability of {MoTp(NO)(DMAP)} was probed by the attempted exchange of (R)-α-pinene with the chiral “reporter ligand” (S)β-pinene: the kinetic stability of the square-pyramidal {MoTp(NO)(DMAP)} intermediate should result in a different diastereomer ratio of the β-pinene products in comparison to that which would occur starting with a racemic source of {MoTp(NO)(DMAP)}. Disappointingly, when the α-pinene complex (RMo,R)-10A was dissolved in a THF solution of (S)-β-pinene (∼0.6 M; 10 equiv), the isolated β-pinene product (15) formed as a mixture of four stereoisomers (∼2:2:2:1). This outcome was then compared to the synthesis of 15 from racemic starting materials: the preparation of 15, either via the exchange from the D

DOI: 10.1021/acs.organomet.8b00027 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics Scheme 6. Ligand Exchange Reactions for the α,α, α-Trifluorotoluene Complex 7a

in a THF solution and allowed to stand, just two diastereomers were formed, in a 1:1 ratio (Figure 5, 16A,B). Alkene resonances

Figure 5. Quadrant perspective of the proposed diastereomers of myrtenal complex 16.

at 5.22 and 5.05 ppm, and proton signals at 4.16 and 4.04 ppm associated with an η2-bound aldehyde (cf. WTp(NO)(PMe3)(η2-acetaldehyde); 4.30 ppm),26 confirmed that the metal is coordinated through the carbonyl in both of these diastereomers. Further, NOESY data indicated that the oxygen is oriented toward the DMAP ligand in both cases (16A,B, Figure 5). When the (R)-α-pinene complex (RMo,R)-10A was dissolved in a 0.3 M THF solution of (1R)-myrtenal (8 equiv), and the solution was allowed to stand for several days, the resulting diastereomer ratio was 0.9:1. When the concentration of myrtenal was raised to 3.3 M, the ratio only marginally improved to 0.6:1. Just as was the case with the (S)-β-pinene reporter, extensive epimerization of {MoTp(NO)(DMAP)} had occurred. In contrast to that observed for the third-row metal complexes, these results suggested that the square-pyramidal Mo(0) intermediate {MoTp(NO)(DMAP)} is highly susceptible to racemization via a trigonal-bipyramidal transition state.7,30 Apparently, racemization of this intermediate is significantly faster for molybdenum, but this begged the question: compared to what? Given that epimerization was almost certainly occurring on the five-coordinate intermediate and not the octahedral product,7,31,32 racemization of {MoTp(NO)(DMAP)} was preempting association of the incoming myrtenal ligand. As seen in Scheme 7, dissociation of the α-pinene (rate = kD[10A]) results in an intermediate that can either isomerize (rate = kI[SP]) or react with the incoming ligand (L). However, unlike racemization, the rate of ligand association (rate = kA[SP][L]) should depend on the concentration of L. Gratifyingly, when this experiment was repeated in NEAT (1R)-myrtenal, a 1H NMR spectrum (Figure 6) of the reaction mixture indicated that 16 was formed in a > 20:1 diastereomer ratio, favoring (RMo,1R)-16A. Repeating the experiment using the (S)-α-pinene complex (SMo,S)-10A resulted in the other diastereomer of the myrtenal complex (SMo,1R)-16B as the major product (dr < 1:20). These observations demonstrate that the stereochemistry of {MoTp(NO)(DMAP)} can be largely conserved through the substitution process, provided that the incoming ligand is kept in high concentration. Most studies concerning racemization of pseudooctahedral “chiral-at-metal” systems have understandably focused on dissociation of a ligand, which is the rate-limiting step that exposes the fluxional square-pyramidal intermediate.7 However, our goal of a universal chiral precursor to enantioenriched molybdenum aromatic complexes depends on the stability of this intermediate, similar to studies by Gladysz32,33 or Meggers.8 Earlier reports from our group with rhenium indicated that ligand substitution with stereochemical retention of {ReTp(CO)(MeIm)} could occur on either Re(I) or Re(II).15 We questioned whether a higher oxidation state of molybdenum could more effectively inhibit epimerization. To test this theory, we repeated the

a Reaction conditions: THF solvent, ∼2 M ligand or neat ligand; 3−5 h, 25 °C.

trifluorotoluene complex 7, or by sodium reduction of racemic MoTp(NO)(DMAP)(I) in a THF solution of (S)-β-pinene (∼6 M; 15 equiv), produced the same ratio of diastereomers (15A−D), as did the exchange from the enantiopure (R)-α-pinene complex (RMo,R)-10A. Just as is the case with (R)-α-pinene, eight stereoisomers are possible for the (S)-β-pinene complex 15. Again, ruling out the isomers with the gem-dimethyl group pointing in toward the metal, β-pinene is able to coordinate through only one face of the alkene, reducing the number of viable stereoisomers from eight to four (Figure 4, 15A−D). However, in contrast to the α-pinene

Figure 4. Quadrant perspective of the four proposed diastereomers of the (S)-β-pinene complexes 15A−D.

isomer, coordination of the β-isomer occurs with only modest steric differentiation. To aid in our interpretation, we performed DFT calculations, which supported the notion that the energies of all four isomers are similar (Figure 4). Given the complex mixture of isomers that was obtained from β-pinene, we shifted our focus to (1R)-myrtenal, the naturally occurring aldehyde derivative of the pinenes. When a racemic mixture of the TFT complex 7 was combined with (1R)-myrtenal E

DOI: 10.1021/acs.organomet.8b00027 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics Scheme 7. Mechanism of Ligand Substitution for α-Pinene Complex (RMo,R)-10A

(RMo,1R)-16A. Remarkably, similar results were obtained when [Co(Cp)2]Tf2N was used as the catalyst, even though the latter metallocenium salt is a much weaker oxidant (−0.78 V; cf. 0.55 V for FeCp2+). We postulate that the improved retention results from the substitution event occurring on Mo(I), rather than Mo(0) (Scheme 7), and that the higher oxidation state improves the stereochemical stability of the purported square-pyramidal intermediate {MoTp(NO)(DMAP)}+. A detailed investigation into the mechanism of this redox-catalyzed substitution process is underway, but for the present study, these findings provide a simple assay to interrogate the configuration of the molybdenum stereocenter for complexes of the form MoTp(NO)(DMAP)(η2-L) (see Figure 6). Unfortunately, the myrtenal assay confirmed what we had feared: while exchange of α-pinene for myrtenal could be carried out with complete retention, when the trifluorotoluene complex 7 was prepared from the pinene complex 10A via ligand exchange at 25 °C, the product was completely racemized. DFT calculations (Supporting Information) support the hypothesis that the intermediate {MoTp(NO)(DMAP)} has a square-pyramidal geometry (SP), and find that the trigonalbipyramidal transition state (TBP) is only 7.2 kcal/mol higher in energy (ΔH(I)*) (Figure 7). However, calculations also indicate

Figure 7. Square-pyramidal (SP; left, right) ground states and transition state (TBP; center) for the isomerization of {MoTp(NO)(DMAP)}.

that the enthalpic barrier to ligand association (ΔH(A)* calculated for L = benzene) is negligible. Hence, we postulated that the main factor contributing to the activation free energy barrier for ligand association likely comes from the entropy of activation (ΔS(A)*), which is expected to be negative for an associative process. Meanwhile, the isomerization of the square-pyramidal intermediate {MoTp(NO)(DMAP)} is likely to have a more modest activation entropy (ΔS(I)*), given that it is an intramolecular process. If these assumptions hold true, the degree to which the configuration of the metal stereocenter is conserved should depend strongly on temperature: As the temperature is lowered, the rate of isomerization should decrease to a greater degree than the rate of ligand association. More specifically, using the Eyring equation, one can show that if ΔH(I)* > ΔH(A)* and ΔS(A)* < ΔS(I)*, then the ratio kA/kI increases as the temperature is decreased (Supporting Information). To get a better sense of this temperature dependence, we modeled rates for isomerization and association from −55 to 45 °C at [L] = 1, 3 M, using the value 7.2 kcal/mol for ΔH(I)* and −24 eu for ΔS(A)*. Values for ΔH(A)* and ΔS(I)* were held to zero. While these numbers are only approximations, the graph in Figure 8 illustrates how the extent of epimerization (kI/(kA[L])) can be highly sensitive to temperature. If reduced temperatures were needed to prevent epimerization of {MoTp(NO)(DMAP)} (SP), an alternative chiral precursor would be required with a leaving group more labile than α-pinene; the dissociation rate of the pinene ligand in 10A would be impractically slow much below ambient temperature. Hence, we considered a new strategy in which the conversion of the α-pinene

Figure 6. 1H NMR signals of the Tp ligand (H4) for the two diastereomers of (1R)-myrtenal complex (RMo,1R)-16A and (SMo,1R)16B, as prepared from α-pinene complexes (SMo,S)-10A (top) and (RMo,R)-10A (bottom) and racemic CF3Ph complex 7 (middle).

substitution outlined in Scheme 7 with a 3.3 M myrtenal solution, but this time with the addition of 0.1 equiv of [Fe(Cp)2]Tf2N to the reaction mixture. In the control reaction, the pinene complex (RMo,R)-10A was dissolved in a 3.3 M solution of (1R)-myrtenal in THF. After several hours, a 0.6:1 ratio of diastereomers 16A,B was obtained. When this reaction was repeated with addition of the Fe(III) catalyst, not only was the reaction dramatically accelerated (from hours to minutes), but also a 1H NMR spectrum of the resulting solution now showed a 20:1 ratio favoring F

DOI: 10.1021/acs.organomet.8b00027 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics

of this purportedly enantioenriched material (S)-3 in neat trifluorotoluene at 15 °C to minimize the chances of either (S)-[MoTp(NO)(DMAP)(I)]− or the desired arene complex (R)-7 isomerizing (see Scheme 7). Once the TFT complex (R)-7 was in hand, a myrtenal assay (preparation of 16 from 7) revealed virtually complete retention of the metal stereocenter (er = 99:1). As discussed at the onset of this report (see Scheme 1), preparation of enantioenriched products from aromatic substrates requires not only the enantioenriched metal complex, but also either high chiral recognition for aromatic binding, or stereoelectronic differentiation in the subsequent reaction with an electrophile. We recently reported that, while the trifluorotoluene complex fails to show any stereoselectivity in binding the prochiral arene, the highly asymmetric electronic structure of {MoTp(NO)(DMAP)} results in a highly selective protonation (Scheme 8).22 Thus, we carried out the conversion of (R)-7 to diene complex (RMo,R)-18 via protonation, followed by addition of the masked enolate 1-methoxy-2-methyl-1-(trimethylsiloxy)propene (MMTP) (63%). Upon liberation from the metal (71%), analysis of the organic diene (R)-19 with chiral HPLC revealed that the diene (er = 99:1) was enantioenriched at levels similar to that for the original pinene source (er ≥ 98:2). When these steps were repeated with the opposite hand of α-pinene, (S)-19 was isolated in 57% with er = 97:3. Finally, we wanted to see if the same modest reduction of temperature used for the preparation of TFT complex (R)-7 would allow the preparation of other complexes in enantioenriched form. Returning to (S)-β-pinene, recall that when a solution of either α-pinene complex (RMo,R)-10A or racemic TFT complex 7 is allowed to stand at 25 °C for 3 days in solution with (S)-β-pinene, the outcome is a 2:2:2:1 mixture of four isomers (15A−D). However, when (S)-3 is reduced at 15 °C in the presence of (S)-β-pinene, the final 1H NMR spectrum of the reaction mixture showed that two of the four isomers are practically absent (Scheme 9 and Figure 9). Presumably, these two

Figure 8. Eyring modeling of the specific rate (y-axis, s−1) of isomerization (kI) and association (kA[L]) as a function of temperature (x-axis, °C) and concentration of L.

complex 10A to an arene complex would be carried out in two steps: the pinene complex would first be oxidized with iodine to provide an enantioenriched form of MoTp(NO)(DMAP)(I) (3), which then would be reduced in the presence of an arene. The purported intermediate [MoTp(NO)(DMAP)(I)]− would be expected to have a much faster rate of dissociation than the α-pinene analogue 10A, and could still be labile at reduced temperatures. However, would the molybdenum stereocenter be conserved through both oxidation and reduction steps? DFT calculations indicate that the square-pyramidal intermediate is indeed more kinetically stable for Mo(I) than for Mo(0) (cf. 10.2 kcal/mol for Mo(I) and 7.2 kcal/mol for Mo(0)), and this increased stability appears to play a key role in the high stereoretention observed for the redox-catalyzed substitution of pinene by myrtenal (vide supra). When a solution of the pinene complex (RMo,R)-10A was treated with iodine, a compound was obtained in >90% yield (4.6 g recovered; Scheme 8) whose spectroscopic and electrochemical features were consistent with MoTp(NO)(DMAP)(I) (3).20 We then carried out the reduction Scheme 8. Conversion of α-Pinene Complex (RMo,R)-10A to Arene Complex 7 and Subsequent Elaboration to an Enantioenriched Diene ((R)-19)

Scheme 9. Selective Formation of (S)-β-Pinene Complex (RMo,S)-15A and (RMo,S)-15C

isomers (15A,C) could only be made from the configuration of the original molybdenum stereocenter in (S)-3, and these observations suggest that even a modest drop in the reaction temperature could allow other enantioenriched complexes to be G

DOI: 10.1021/acs.organomet.8b00027 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics

alkene with dramatic differences in the steric profile of the alkene diastereofaces. The stark difference in how α-pinene interacts with Tp for a given metal configuration (see Figure 3) will likely translate to other transition-metal complexes with scorpionate ligands.34 As part of these studies, an unusual mechanism for ligand substitution with aldehydes and ketones was revealed in which a catalytic amount of a mild one-electron oxidant (e.g., FeCp2+, CoCp2+) rapidly accelerates exchange of α-pinene for (1R)myrtenal, with complete retention of the metal stereocenter. We hypothesize that the addition of the catalyst effectively transfers the substitution event to Mo(I), where isomerization of {MoTp(NO)(DMAP)} is minimized. Efforts continue in our laboratory to investigate this mechanism and to evaluate the potential of redox catalysis to prepare enantioenriched Mo(0) arene, alkene, and carbonyl complexes directly from MoTp(NO)(DMAP)(η2-α-pinene). More broadly, this study highlights the strategic use of redox catalysts and stable neighboring oxidation states as tools for exploring asymmetric reactions in organometallic chemistry.6,7

Figure 9. 1H NMR signals of the DMAP methyl groups for the four isomers of (S)-β-pinene complex 15A−D, as prepared from enantioenriched (S)-3: (top) t = 15 °C; (bottom) t = 25 °C.

■

prepared from (S)-3 as long as the ligand concentration is kept high during reduction.

■

EXPERIMENTAL SECTION

General Methods. NMR spectra were obtained on a 600 or 800 MHz spectrometer. All chemical shifts are reported in ppm, and proton and carbon shifts are referenced to tetramethylsilane (TMS) utilizing residual 1 H or 13C signals of the deuterated solvents as an internal standard. Fluorine chemical shifts are referenced to a solution of hexafluorobenzene in acetone-d6 (−164.9 ppm relative to CFCl3) contained in a capillary tube. Coupling constants (J) are reported in hertz (Hz). Infrared spectra (IR) were recorded as a glaze on a spectrometer fitted with a horizontal attenuated total reflectance (HATR) accessory or on a diamond anvil ATR assembly. Electrochemical experiments were performed under a dinitrogen atmosphere. Cyclic voltammetry data were taken at ambient temperature (∼25 °C) at 100 mV/s in a standard three-electrode cell with a glassy-carbon working electrode, N,N-dimethylacetamide (DMA) or acetonitrile (CH3CN) solvent (unless otherwise specified), and tetrabutylammonium hexafluorophosphate (TBAH) electrolyte (approximately 0.5 M). All potentials are reported versus NHE (normal hydrogen electrode) using cobaltocenium hexafluorophosphate (E1/2 = −0.78 V), ferrocene (E1/2 = +0.55 V), or decamethylferrocene (E1/2 = +0.04 V) as internal standard. The peak-to-peak separation was less than 100 mV for all reversible couples. Unless otherwise noted, all synthetic reactions were performed in a glovebox under a dry nitrogen atmosphere. Deuterated solvents were used as received. Pyrazole (Pz) protons of the hydrido tris(pyrazolyl)borate (Tp) ligand were uniquely assigned (e.g., “Pz3B”) using a combination of two-dimensional NMR data and (dimethylamino)pyridine−proton NOE interactions. When unambiguous assignments were not possible, Tp protons were labeled as “Pz3/5 or Pz4”. All J values for Pz protons are 2(±0.2) Hz. BH peaks (around 4−5 ppm) are not identified due to their quadrupole broadening; IR data are used to confirm the presence of a BH group (around 2500 cm−1). Compounds 3,20 4,20 7,22 18,22 and 1919,22 were previously reported. (S)-MoTp(NO)(DMAP)(I) ((S)-3). (RMo,R)-10A (5.23 g, 8.76 mmol) and THF (20 mL) were placed in a 125 mL filter flask charged with a stir bar. A solution of I2 (1.11 g, 4.38 mmol) dissolved in Et2O (20 mL) was placed in the flask. The green mixture was stirred for 15 min and then evaporated to dryness in vacuo. The resulting green solid was dissolved in CH2Cl2 (5 mL) and added to stirring hexanes (200 mL), yielding a green precipitate. This solid was collected on a 150 mL fine-porosity fritted disk, washed with hexanes (3 × 50 mL), and desiccated for 1 h to yield (S)-3 (4.60 g, 93%). (R)-MoTp(NO)(DMAP)(I) ((R)-3). (SMo,S)-10A (4.01 g, 6.72 mmol) and THF (5 mL) were placed in a 125 mL filter flask charged with a stir bar. A solution of I2 (852 mg, 3.35 mmol) dissolved in Et2O (20 mL) was placed in the flask. The green mixture was stirred for 15 min and then evaporated to dryness in vacuo. The resulting green solid was dissolved

CONCLUDING REMARKS MoTp(NO)(DMAP)(I) (3) is a direct precursor to a broad family of complexes containing unsaturated organic molecules of the form MoTp(NO)(DMAP)(η2-L). We have demonstrated that 3 can be resolved in two steps (er = 99:1) via an α-pinene intermediate, available as either enantiomer, on a large scale (4.6 g recovered; 93−98%). When a solution of this compound was reduced with sodium at 15 °C in the presence of either α,α, α-trifluorotoluene or β-pinene, the configuration of the metal stereocenter in the resulting compound was conserved. The enantioenriched form of the trifluorotoluene analogue was then elaborated into an enantioenriched cyclohexadiene product to demonstrate proof of concept. One can envision that such a strategy could lead to a diverse range of enantioenriched organic compounds, derived from a diverse family of aromatic substrates, with chirality originating from a single, universal precursor.28 While enantioenriched η6-arene complexes have been used as precursors to enantioenriched organics,9 an approach involving a universal chiral-at-metal precursor has not been realized. As was the case with its rhenium and tungsten predecessors, the only stereochemical element in MoTp(NO)(DMAP)(I) is the arrangement of ligands about the metal. As such, its configurational stability during the process of reduction followed by replacement of iodide with an aromatic substrate depends on the stereochemical retention of the square-pyramidal intermediate {MoTp(NO)(DMAP)}. In this regard, the second-row element presents a special challenge, as its barrier to epimerization is lower than that encountered with the heavy-metal analogues {ReTp(CO)(MeIm)} and {WTp(NO)(PMe3)}. However, reduced temperatures, high concentration of incoming ligand, and increased oxidation state of the metal appear to minimize racemization. How broadly these concepts apply to other systems is an open question, but the implications to asymmetric catalysis are clear, especially in those systems that pass through fivecoordinate intermediates. Chiral-at-metal systems avoid the synthesis of special ligands and put the asymmetric element directly at the metal, where key bond-forming reactions occur.6,7 We also note the special role that α-pinene has played in this chemistry, as well as that with Tp complexes of rhenium and tungsten.15,17 α-Pinene represents a completely rigid, trisubstituted H

DOI: 10.1021/acs.organomet.8b00027 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics

(1H, d, J = 10.1, H5), 2.50 (2H, m, H3) 2.24, (1H, t, J = 5.7, H6), 2.18 (2H, m, H2 and H5), 1.80 (1H, m, H4), 1.36 (3H, s, α-pinene Me), 1.13 (3H, s, α-pinene Me), 0.60 (3H, s, α-pinene vinyl Me). 13C NMR (acetone-d6, δ): 159.0 (DMAP C4), 151.3 (DMAP C2, C6), 145.0 (Pz3A), 143.1 (Pz3C), 141.5 (Pz3B), 137.2 (Pz5A/C), 136.3 (Pz5A/C), 135.2 (Pz5B), 108.3 (DMAP C3, C5), 106.6 (Pz4), 106.1 (Pz4), 106.0 (Pz4), 82.2 (pinene quat, sp2), 68.4 (C2), 55.9 (C6), 42.9 (C4), 42.3 (pinene quat, sp3), 39.1 (DMAP Me), 32.1 (C3), 31.1 (C5), 27.9 (pinene gem Me), 27.8 (pinene alkene Me), 23.3 (pinene gem Me). Anal. Calcd for C26H36BMoN9O: C, 52.27; H, 6.07; N, 21.10. Found: C, 52.46; H, 6.03; N, 21.20. (SMo,S)-MoTp(NO)(DMAP)(η2-α-pinene) ((SMo,S)-10A). Sodium dispersion (30−35% by weight, 3.12 g, 0.046 mol) and hexanes (200 mL) were placed in a 250 mL round-bottom flask charged with a stir egg. The gray mixture that formed was vigorously stirred for 18 h, after which the hexanes was decanted away. THF (50 mL), (S)-α-pinene (12.5 g, 0.092 mol, ee = 97%), and 3 (6.09 g, 0.010 mol) were added. The resulting green mixture was stirred at 25 °C for 1 h, and then Et2O (175 mL) was added to the reaction mixture. This blue solution was chromatographed through a 150 mL fine-porosity fritted disk threefourths full with SiO2, and the product was eluted with Et2O (250 mL). This orange filtrate was concentrated in vacuo to ∼10 mL and added to stirred hexanes (100 mL), yielding an orange precipitate. This solid was collected on a 60 mL fine-porosity fritted disk, washed with hexanes (3 × 60 mL), and desiccated for 1 h to yield (SMo,S)-10A (3.05 g, 50% yield). MoTp(NO)(DMAP)(η2-acetone) (11). 7 (0.543 g, 0.894 mmol), THF (4 mL), and acetone (0.500 g, 8.61 mmol) were placed in a 4 dram vial charged with a stir pea. The resulting red solution was stirred at 25 °C for 3 h. The reaction mixture was then slowly added to 30 mL of stirred pentane, yielding a white precipitate. The precipitate was isolated on a 15 mL fine-porosity fritted disk, washed with chilled pentane (2 × 10 mL), and dried under vacuum for 2 h to yield 11 (0.401 g, 86%).22 MoTp(NO)(DMAP)(η2-ethyl acetate) (12). 7 (0.490 g, 0.79 mmol), THF (3 mL), and ethyl acetate (0.730 g, 8.29 mmol) were placed in a 4 dram vial charged with a stir pea. The resulting red solution was stirred at room temperature for 3 h. The reaction mixture was then slowly added to 30 mL of stirred pentane, yielding a white precipitate. The precipitate was isolated on a 15 mL fine-porosity fritted disk, washed with chilled pentane (2 × 10 mL), and dried under vacuum for 2 h to yield 12 (0.283 g, 64%). CV: Ep,a = +0.72 V. IR: νNO 1540 cm−1; νBH 2487 cm−1. 1H NMR (acetone-d6, δ): 8.07 (1H, d, Pz3/5), 8.02 (1H, d, Pz3/5), 7.99 (1H, d, Pz3/5), 7.95 (1H, d, Pz3/5), 7.62 (2H, m, DMAP H2, H6), 7.45 (1H, d, Pz3/5), 7.09 (1H, d, Pz3/5), 6.69 (2H, m, DMAP H3, H5), 6.39 (1H, t, Pz4), 6.34 (1H, t, Pz4), 6.20 (1H, t, Pz4), 3.84 (1H, m, EtOAc CH2), 3.77 (1H, m, EtOAc CH2), 3.00 (6H, s, DMAP Me), 1.20 (3H, t, J = 5.2, EtOAc Me), 0.78 (3H, s, EtOAc Me). 13 C NMR (acetone-d6, δ): 170.8 (carbonyl), 151.9 (DMAP C4), 151.6 (DMAP C2, C6), 143.5 (Pz3/5), 143.2 (Pz3/5), 143.0 (Pz3/5), 137.0 (Pz3/5), 136.4 (Pz3/5), 136.1 (Pz3/5), 107.4 (DMAP C3, C5), 107.0 (Pz4), 106.8 (Pz4), 106.3 (Pz4), 60.5 (EtOAc CH2), 39.0 (DMAP Me) 25.8 (EtOAc Me), 16.7 (EtOAc Me). Attempts to further purify for elemental analysis led to decomposition. MoTp(NO)(DMAP)(η2-acetonitrile) (13). 7 (0.300 g, 0.494 mmol) and acetonitrile (3.93 g, 95.7 mmol) were placed in a 4 dram vial charged with a stir pea. The resulting orange mixture was stirred at room temperature for 5 h. The resulting brown reaction mixture was then evaporated in vacuo to a film. The resulting film was dissolved in CH2Cl2 (2 mL) and slowly added to stirred pentane (30 mL), yielding a light green precipitate. The precipitate was isolated on a 15 mL fine-porosity fritted disk, washed with a 4/1 pentane/diethyl ether mixture (4 × 30 mL), and dried under static vacuum for 2 h to yield 13 (0.165 g, 67%). CV: Ep,a = +0.03 V. IR: νNO 1566 cm−1; νBH 2470 cm−1. 1H NMR (CD3CN, δ): two isomers present in a ratio of 1:0.3, major isomer, 7.97 (1H, d, Pz5A), 7.87 (1H, d, Pz3A), 7.84 (1H, d, Pz3B), 7.75 (1H, d, Pz3C), 7.68 (2H, m, DMAP H2, H6), 7.44 (1H, d, Pz5B), 6.92 (1H, d, Pz5C), 6.51 (2H, m, DMAP H3, H5), 6.36 (1H, t, Pz4A), 6.25 (1H, t, Pz4B), 6.12 (1H, t, Pz4C), 2.99 (6H, s, DMAP Me), 2.18 (3H, s, Me); minor isomer, 7.98 (1H, d, Pz3/5), 7.85 (1H, d, Pz3/5), 7.84 (1H, d, Pz3/5), 7.76 (1H, d, Pz3/5), 7.70 (2H, bs, DMAP H2, H6), 7.16 (1H, d, Pz3/5), 6.99 (1H, d, Pz4), 6.57 (2H, bd, DMAP H3, H5), 6.32 (1H, t, Pz4), 6.22 (1H, t, Pz4),

in CH2Cl2 (5 mL) and added to stirring hexanes (250 mL), yielding a green precipitate. This solid was collected on a 30 mL fine-porosity fritted disk, washed with hexanes (3 × 50 mL), and desiccated for 1 h to yield (R)-3 (3.90 g, 99%). MoTp(NO)(DMAP)(η2-naphthalene) (4). 7 (0.524 g, 0.863 mmol), THF (5 mL), and naphthalene (1.05 g, 8.25 mmol) were placed in a 4 dram vial, and the resulting brown solution was stirred at room temperature for 4 h. This reaction mixture was then slowly added to stirring pentane (50 mL), yielding a yellow precipitate. This precipitate was isolated on a 15 mL fine-porosity fritted disk, washed with chilled pentane (2 × 15 mL), and dried under static vacuum for 2 h to yield 4 (0.399 g, 78%). (R)-MoTp(NO)(DMAP)(η2-α,α,α-trifluorotoluene) ((R)-7). Sodium dispersion (30−35% by mass, 5.10 g, 0.067 mol) and hexanes (100 mL) were placed in a 100 mL round-bottom flask charged with a stir pea. The gray mixture was vigorously stirred for 18 h, at which point the hexanes were decanted off. Next, α,α,α-trifluorotoluene (50 mL) was placed in the flask, which was chilled to 15 °C for 15 min. (S)-3 (4.50 g, 7.65 mmol) was added, and the green mixture was stirred at 15 °C for 24 h. The resulting red mixture was then chilled to −30 °C, filtered through a 60 mL medium-porosity fritted disk, and washed with Et2O (3 × 60 mL). The resulting precipitate, containing sodium, was then transferred to a 50 mL beaker charged with a stir bar, suspended in Et2O (20 mL), and stirred rapidly. Next, the stirring was stopped, and the mixture was decanted into a 125 mL Erlenmeyer flask, taking care to prevent the sodium from being transferred. Et2O (20 mL) was placed in the beaker containing the sodium, and the red mixture was transferred to the aforementioned 125 mL Erlenmeyer flask. While the box was purged with nitrogen, MeOH (5 mL) was added to the red mixture dropwise, yielding a red precipitate. This precipitate was then collected on a 30 mL fine-porosity fritted disk, washed with Et2O (4 × 30 mL), and desiccated for 2 h to yield the solid (R)-7 (3.02 g, 65%). (S)-MoTp(NO)(DMAP)(η2-α,α,α-trifluorotoluene) ((S)-7). Sodium dispersion (30−35% by mass, 3.12 g, 0.041 mol) and hexanes (100 mL) were placed in a 100 mL round-bottom flask charged with a stir bar. The gray mixture was vigorously stirred for 18 h, at which point the hexanes were decanted off. Next, α,α,α-trifluorotoluene (30 mL) was placed in the flask, which was chilled to 15 °C for 15 min. (R)-3 (3.02 g, 5.13 mmol) was added, and the green mixture was stirred at 15 °C for 24 h. The resulting red mixture was then chilled to −30 °C, filtered through a 60 mL medium-porosity fritted disk, and washed with Et2O (3 × 30 mL). The resulting precipitate, containing sodium, was then transferred to a 50 mL beaker charged with a stir bar, suspended in Et2O (20 mL), and stirred rapidly. Next, the stirring was stopped, and the mixture was decanted into a 125 mL Erlenmeyer flask, taking care to prevent the sodium from being transferred. Et2O (20 mL) was placed in the beaker containing the sodium, and the red mixture was placed in the Erlenmeyer flask. While the box was purged with nitrogen, MeOH (5 mL) was added to the red mixture dropwise, yielding a red precipitate. This precipitate was then collected on a 30 mL fine-porosity fritted disk, washed with H2O (30 mL) and Et2O (4 × 30 mL), and desiccated for 2 h to yield the solid (S)-7 (1.41 g, 45%). (RMo,R)-MoTp(NO)(DMAP)(η2-α-pinene) ((RMo,R)-10A). Sodium dispersion (30−35% by mass, 12.23 g, 0.159 mol) and hexanes (500 mL) were placed in a 1 L round-bottom flask charged with a stir egg. The gray mixture was vigorously stirred for 18 h, after which the hexanes was decanted away. THF (200 mL), (R)-α-pinene (25 g, 0.427 mol; ee = 97%), and 3 (25.10 g, 0.043 mol) were added, and the resulting green mixture was stirred at 25 °C for 1.5 h; then Et2O (775 mL) was added to the reaction mixture. This blue solution was chromatographed through a 600 mL fine-porosity fritted disk three-fourths full with SiO2, and the product was eluted with Et2O (1 L). The orange filtrate was concentrated in vacuo to 25 mL and then added to stirred hexanes (400 mL), which resulted in an orange precipitate. This solid was collected on a 150 mL fine-porosity fritted disk, washed with hexanes (3 × 150 mL), and desiccated for 1 h to yield (RMo,R)-10A (11.02 g, 43% yield). CV: Ep,a = −0.17 V. IR: νNO 1548 cm−1; νBH 2441 cm−1. 1H NMR (acetoned6, δ): 8.21 (2H, m, DMAP H2, H6), 7.90 (1H, d, Pz5A/C), 7.85 (1H, d, Pz5A/C), 7.77 (1H, d, Pz3C), 7.73 (1H, d, Pz5B), 7.66 (1H, d, Pz3A), 7.11 (1H, d, Pz3B), 6.69 (2H, m, DMAP H3, H5), 6.31 (2H, t, Pz4A and Pz4C), 6.10 (1H, t, Pz4B), 3.08 (6H, s, DMAP Me), 2.61 I

DOI: 10.1021/acs.organomet.8b00027 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics 6.15 (1H, t, Pz4), 3.00 (6H, s, DMAP Me), 2.37 (3H, s, Me). 13C NMR (CD3CN, δ): 174.2, 174.2, 155.3, 155.3, 152.1, 145.9, 144.7, 144.7, 143.2, 143.0, 142.5, 142.1, 137.2, 136.7, 136.6, 136.5, 136.4, 108.4, 106.9, 106.7, 106.4, 39.4, 15.2, 15.2. Anal. Calcd for C18H23BMoN10O·H2O: C, 41.54; H, 4.84; N, 26.92. Found: C, 41.71; H, 4.61; N, 26.44. (S)-MoTp(NO)(DMAP)(η2-β-pinene) (15). Sodium dispersion (30−35% by mass, 6.07 g, 0.079 mol) and hexanes (100 mL) were placed in a 100 mL round-bottom flask charged with a stir bar. The gray mixture was stirred at 1150 rpm for 18 h, at which point the hexanes were decanted off. THF (50 mL), (S)-β-pinene (50 mL, 0.317 mol), and 3 (12.13 g, 0.020 mol) were placed in the reaction flask, and the resulting green mixture was stirred at room temperature for 24 h. The reaction mixture was loaded onto a 150 mL fine-porosity fritted disk three-fourths full with SiO2, and was washed with hexanes (200 mL), which was discarded. The product was eluted with Et2O (400 mL) as a yellow fraction, which was concentrated in vacuo to 20 mL. Hexanes (100 mL) was added, and the resulting yellow precipitate was collected on a 60 mL fine-porosity fritted disk, washed with hexanes (3 × 150 mL), and desiccated for 1 h, to yield 15 as a mixture of four isomers (1.70 g, 14%). CV: Ep,a = −0.20 V. IR: νNO 1557 cm−1; νBH 2425 cm−1. Anal. Calcd for C26H36BMoN9O·1/ 3C6H14: C, 53.71; H, 6.55; N, 20.13. Found: C, 53.55; H, 6.20; N, 20.26. (R Mo ,1R)-MoTp(NO)(DMAP)(η 2 -myrtenal) ((R Mo ,1R)-16). (RMo,R)-10A (500 mg, 0.837 mmol), a solution of CH2Cl2 (5 mL), FeCp2PF6 (25 mg, 0.075 mmol), and (1R)-myrtenal (300 mg, 1.99 mmol) was placed in a 4 dram vial charged with a stir bar. The resulting mixture was stirred at room temperature for 45 min. The reaction mixture was then evaporated in vacuo to a green film. The film was dissolved in THF (1 mL), and the resulting solution was loaded onto a 30 mL fine-porosity fritted disk three-fourths full with SiO2. The product was eluted as a yellow-green band with Et2O (50 mL). This filtrate was evaporated to dryness in vacuo. The solid was dissolved in CH2Cl2 (1 mL) and added to stirred hexanes (50 mL), yielding a green precipitate. The precipitate was isolated on a 15 mL fine-porosity fritted disk, and the filtrate was evaporated to dryness in vacuo to yield (RMo,1R)-16 as a beige solid (32 mg, 6%). CV: Ep,a = +0.27 V. IR: νNO 1577 cm−1; νBH 2481 cm−1. 1H NMR (acetoned6, δ): 8.06 (1H, d, Pz5A), 7.95 (1H, d, Pz3B), 7.86 (2H, 2 d, Pz3A and Pz3C), 7.65 (2H, m, DMAP H2, H6), 7.53 (1H, d, Pz5B), 7.37 (1H, d, Pz5C), 6.58 (2H, m, DMAP H3, H5), 6.29 (1H, t, Pz4B), 6.27 (1H, t, Pz4A), 6.18 (1H, t, Pz4C), 5.05 (1H, bs, C2), 4.04 (1H, s, COH), 3.08 (6H, s, DMAP Me), 2.75 (1H, m, myrtenal H5b), 2.60 (2H, m, myrtenal H6, H5b), 2.54 (1H, m, myrtenal H3), 2.14 (1H, m, myrtenal H4), 1.52 (1H, d, J = 9.3 myrtenal H3), 1.38 (3H, s, myrtenal C5a Me), 0.97 (3H, 2, myrtenal C5a Me). 13C NMR (acetone-d6, δ): 155.2 (C1), 154.7 (DMAP C4), 150.6 (DMAP C2, C6), 142.3 (PzB5), 141.9 (Pz5A), 141.1 (Pz5C), 135.8 (Pz3C), 135.5 (Pz3A), 135.3 (PzB3), 115.7 (C2), 106.6 (DMAP C3, C5), 105.8 (Pz4B), 105.2 (Pz4C), 105.0 (Pz4A), 98.5 (aldehyde), 41.2 (C4), 40.9 (C6), 38.3 (DMAP Me), 37.1 (C5a), 31.9 (C3), 31.5 (C5b), 26.2 (C5a Me), 20.9 (C5a Me). Anal. Calcd for C26H34BMoN9O2·1/2CH2Cl2: C, 48.68; H, 5.40; N, 19.28. Found: C, 49.39; H, 5.59; N, 19.50. (S Mo ,1R)-MoTp(NO)(DMAP)(η 2 -myrtenal) ((S Mo ,1R)-16). (SMo,S)-10A (500 mg, 0.837 mmol), CH2Cl2 (5 mL), FeCp2PF6 (25 mg, 0.0755 mmol), and (1R)-myrtenal (300 mg, 1.997 mmol) were placed in a 4 dram vial charged with a stir pea. The resulting mixture was stirred at 25 °C for 45 min. The reaction mixture was evaporated in vacuo to a green film. The film was dissolved in THF (1 mL) and loaded onto a 30 mL fine-porosity fritted disk three-fourths full with SiO2. The product was eluted as a yellow-green band with Et2O (50 mL), and the fraction was evaporated to dryness in vacuo. The solid was dissolved in CH2Cl2 (1 mL) and added to stirred hexanes (50 mL), yielding a green precipitate. This precipitate was isolated on a 15 mL fine-porosity fritted disk, and the filtrate was evaporated in vacuo to yield (SMo,1R)-16 as a beige solid (34 mg, 6%). CV: Ep,a = +0.27 V. IR: νNO 1573 cm−1; νBH 2480 cm−1. 1H NMR (acetone-d6, δ): 8.25(1H, d, Pz5A), 7.96 (1H, d, Pz3B), 7.86 (1H, d, Pz3C), 7.84(1H, d, Pz3A), 7.61 (1H, d, Pz5B), 7.57 (2H, m, DMAP H2, H6), 7.38 (1H, d, Pz5C), 6.57 (2H, m, DMAP H3, H5), 6.32 (1H, t, Pz4B), 6.27 (1H, t, Pz4A), 6.16 (1H, t, Pz4C), 5.22 (1H, bs, C2), 4.16 (1H, s, aldehyde proton), 3.08 (6H, s, DMAP Me), 2.75 (1H, d, myrtenal H5b), 2.66 (1H, d, myrtenal H6), 2.56 (1H, d, myrtenal H5b), 2.47 (1H, d, J = 9.3 myrtenal H3), 2.15

(1H, d, myrtenal H4), 1.38 (3H, s, myrtenal C5a Me), 1.29 (1H, d, myrtenal H3), 1.20 (3H, s, myrtenal C5a Me). 13C NMR (acetone-d6, δ): 156.8, (C1) 155.5 (DMAP C4), 151.4 (DMAP C2, C6), 144.1 (Pz5A), 143.1 (PzB5), 142.1 (Pz5C), 136.6 (PzB3), 136.4 (Pz3A/C), 136.2 (Pz3A/C), 116.8 (C2), 107.4 (DMAP C3, C5), 106.8 (Pz4B), 106.1 (Pz4C), 106.0 (Pz4A), 100.0 (aldehyde), 42.2 (C4), 42.0 (C6), 39.2 (C5a), 38.7 (C3), 32.6 (C3), 32.4 (C5b), 26.9 (C5Me), 22.1 (C5Me). (S M o ,S)-MoTp(NO)(DMAP)(η 2 -methyl 2-methyl-2-(5(trifluoromethyl)cyclohexa-2,4-dien-1-yl)propanoate) ((SMo,S)18). (S)-7 (400 mg, 0.659 mmol) and CH3CH2CN (5 mL) were placed in a test tube, and the resulting orange mixture was cooled for 15 min at −60 °C. A −60 °C, 1 M solution of HOTf in CH3CH2CN (246 mg, 1.64 mmol) was added to the reaction mixture, and the resulting red solution was left standing at −60 °C for 15 min. MTDA (0.8 mL, 3.92 mmol) was added to the reaction mixture, and the resulting red solution was stirred at −60 °C for 18 h. A −60 °C solution of triethylamine (1.0 mL, 7.2 mmol) was added to the reaction mixture, and the resulting brown solution was chromatographed through a 60 mL medium-porosity fritted disk three-fourths full with SiO2. The product was eluted with 1/1 Et2O/benzene (100 mL) as a yellow band, and the resulting fraction was concentrated in vacuo. The resulting yellow oil was dissolved in CH2Cl2 (1 mL), and the product was precipitated in stirred pentane (20 mL). The precipitate was collected on a 15 mL fineporosity fritted disk, washed with pentane (3 × 50 mL), and desiccated for 15 min, yielding the light yellow solid (SMo,S)-18 (200 mg, 42%). (R M o ,R)-MoTp(NO)(DMAP)(η 2 -methyl 2-methyl-2-(5(trifluoromethyl)cyclohexa-2,4-dien-1-yl)propanoate) ((RMo,R)18). (R)-7 (1.52 g, 2.47 mmol), CH3CH2CN (15 mL), and a stir bar were placed in a 25 mL round-bottom flask, and the resulting orange mixture was cooled for 15 min at −60 °C. A −60 °C, 1 M solution of HOTf in CH3CH2CN (6.0 mL, 6.0 mmol) was added to the reaction mixture, and the resulting red solution was left standing at −60 °C for 15 min. Then a −60 °C solution of MTDA (3.0 mL, 14.8 mmol) was added to the reaction mixture, and the resulting red solution was stirred at −60 °C for 18 h. A −60 °C solution of triethylamine (3.0 mL, 21.5 mmol) was added to the reaction mixture, and the resulting brown solution was chromatographed through a 150 mL medium-porosity fritted disk three-fourths full with SiO2. The product was eluted with 1/1 Et2O/benzene (500 mL) as a yellow band, and the resulting fraction was concentrated in vacuo. The resulting yellow oil was dissolved in CH2Cl2 (1 mL), and the product was precipitated in stirred pentane (50 mL). The precipitate was collected on a 15 mL fine-porosity fritted disk, washed with pentane (3 × 15 mL), and desiccated for 15 min, yielding the light yellow solid (RMo,R)-18 (1.11 g, 63%). (S)-Methyl 2-Methyl-2-(5-(trifluoromethyl)cyclohexa-2, 4-dien-1-yl)propanoate ((S)-19). (SMo,S)-18 (50 mg, 0.073 mmol), THF (3 mL), and a 0.06 M solution of I2/Et2O (0.6 mL, 0.036 mmol) were placed in a 50 mL filter flask charged with a stir pea. The resulting green solution was stirred at room temperature for 5 min and concentrated in vacuo. The oil was dissolved in CH2Cl2 (1 mL), and the subsequent solution was added to stirred pentane (25 mL). The green precipitate was collected on a 15 mL fine-porosity fritted disk, washed with pentane (3 × 10 mL), and desiccated to recover 3 (31 mg, 76%). The filtrate was removed from the glovebox and evaporated in vacuo to a brown oil to yield methyl (S)-19 (12.5 mg, 71%). (R)-Methyl 2-Methyl-2-(5-(trifluoromethyl)cyclohexa-2, 4-dien-1-yl)propanoate ((R)-19). (RMo,R)-18 (1.00 g, 1.41 mmol), THF (5 mL), I2 (178 mg, 0.70 mmol), and Et2O (10 mL) were placed in a 50 mL filter flask charged with a stir pea. The resulting green solution was stirred at room temperature for 5 min and then evaporated to dryness in vacuo. The solid was dissolved in CH2Cl2 (2 mL), and the subsequent solution was added to stirred hexanes (100 mL). The green precipitate was collected on a 15 mL fine-porosity fritted disk, washed with hexanes (3 × 10 mL), and desiccated to recover 3 (621 mg, 75%). The filtrate was removed from the glovebox and concentrated in vacuo. The resulting brown oil was loaded onto a 250 μm silica preparatory plate (4 × 0.3 mL of CH2Cl2) and was eluted with 10% EtOAc/hexanes (HPLC grade, 200 mL). A KMnO4 positive band at Rf = 0.71−1.00 was isolated and sonicated in EtOAc (HPLC grade, 50 mL) for 10 min. The silica was then filtered off on a 30 mL fine-porosity fritted disk and was J

DOI: 10.1021/acs.organomet.8b00027 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics washed with EtOAc (3 × 15 mL). The filtrate was concentrated in vacuo and dried for 1 h, yielding the colorless oil (R)-19 (197 mg, 57%). Myrtenal Test of (R)-MoTp(NO)(DMAP)(α,α,α-trifluorotoluene) ((R)-7). (1R)-Myrtenal (25 mg, 0.166 mmol), FeCp2PF6 (2 mg, 0.006 mmol), and (R)-7 (25 mg, 0.041 mmol) were placed in a 4 dram vial. CD2Cl2 (0.7 mL) was placed in the vial, and the resulting brown solution was shaken gently for 5 min. A 0.2 mL portion of the solution was added to acetone-d6 (0.5 mL) and analyzed by 1H NMR.

■

(18) Lankenau, A. W.; Iovan, D. A.; Pienkos, J. A.; Salomon, R. J.; Wang, S.; Harrison, D. P.; Myers, W. H.; Harman, W. D. J. Am. Chem. Soc. 2015, 137, 3649−3655. (19) Wilson, K. B.; Myers, J. T.; Nedzbala, H. S.; Combee, L. A.; Sabat, M.; Harman, W. D. J. Am. Chem. Soc. 2017, 139, 11401−11412. (20) Myers, J. T.; Dakermanji, S. J.; Chastanet, T. R.; Shivokevich, P. J.; Strausberg, L. J.; Sabat, M.; Harman, W. D. Organometallics 2017, 36, 543−555. (21) Myers, J. T.; Shivokevich, P. J.; Pienkos, J. A.; Sabat, M.; Myers, W. H.; Harman, W. D. Organometallics 2015, 34, 3648−3657. (22) Myers, J. T.; Smith, J. A.; Dakermanji, S. J.; Wilde, J. H.; Wilson, K. B.; Shivokevich, P. J.; Harman, W. D. J. Am. Chem. Soc. 2017, 139, 11392−11400. (23) Morrison, J. D. In Asymmetric Synthesis; Academic Press: Orlando, FL, 1983; Vol. 1. (24) Meiere, S. H.; Keane, J. M.; Gunnoe, T. B.; Sabat, M.; Harman, W. D. J. Am. Chem. Soc. 2003, 125, 2024−2025. (25) Meiere, S. H.; Harman, W. D. Organometallics 2001, 20, 3876− 3883. (26) Graham, P. M.; Mocella, C. J.; Sabat, M.; Harman, W. D. Organometallics 2005, 24, 911−919. (27) Mocella, C. J.; Delafuente, D. A.; Keane, J. M.; Warner, G. R.; Friedman, L. A.; Sabat, M.; Harman, W. D. Organometallics 2004, 23, 3772−3779. (28) Liebov, B. K.; Harman, W. D. Chem. Rev. 2017, 117, 13721− 13755. (29) Brooks, B. C.; Meiere, S. H.; Friedman, L. A.; Carrig, E. H.; Gunnoe, T. B.; Harman, W. D. J. Am. Chem. Soc. 2001, 123, 3541−3550. (30) Brunner, H. In Theoretical Inorganic Chemistry; Jørgensen, C. K., Brunner, H., Pignolet, L. H., Vepiek, S., Eds.; Springer Berlin Heidelberg: Berlin, Heidelberg, 1975; p 67. (31) Faller, J. W.; Haitko, D. A.; Adams, R. D.; Chodosh, D. F. J. Am. Chem. Soc. 1979, 101, 865−876. (32) Dewey, M. A.; Gladysz, J. A. Organometallics 1990, 9, 1351−1353. (33) Merrifield, J. H.; Strouse, C. E.; Gladysz, J. A. Organometallics 1982, 1, 1204−1211. (34) Trofimenko, S. Polyhedron 2004, 23, 197−203.

ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.organomet.8b00027. 1 H and 13C NMR spectra for selected compounds and description of DFT calculations (PDF) Cartesian coordinates of calculated structures (XYZ)

■

AUTHOR INFORMATION

Corresponding Author

*E-mail for W.D.H.: [email protected]. ORCID

W. Dean Harman: 0000-0003-0939-6980 Author Contributions †

P.J.S. and J.T.M. contributed equally.

Notes

The authors declare no competing financial interest.

■

ACKNOWLEDGMENTS The authors gratefully acknowledge the National Science Foundation (CHE-1152803), and the valuable assistance of Ms. Nichole A. Schwartz.

■

REFERENCES

(1) Brunner, H. Angew. Chem., Int. Ed. Engl. 1969, 8, 382−383. (2) Faller, J. W.; Lavoie, A. R.; Parr, J. Chem. Rev. 2003, 103, 3345− 3368. (3) Gladysz, J. A.; Boone, B. J. Angew. Chem., Int. Ed. Engl. 1997, 36, 550−583. (4) Davies, S. G. Aldrichchim. Acta 1990, 23, 31−37. (5) Liebeskind, L. S.; Welker, M. E.; Fengl, R. W. J. Am. Chem. Soc. 1986, 108, 6328−6343. (6) Amouri, H. Chirality in transition metal chemistry: molecules, supramolecular assemblies and materials; Wiley: Chichester, U.K., 2008. (7) Bauer, E. B. Chem. Soc. Rev. 2012, 41, 3153−3167. (8) Huo, H.; Fu, C.; Harms, K.; Meggers, E. J. Am. Chem. Soc. 2014, 136, 2990−2993. (9) Kündig, E. P. Transition Metal Arene Complexes in Organic Synthesis and Catalysis; Springer: Berlin, 2004; Vol. 7. (10) Harman, W. D. Chem. Rev. 1997, 97, 1953−1978. (11) Graham, P. M.; Meiere, S. H.; Sabat, M.; Harman, W. D. Organometallics 2003, 22, 4364−4366. (12) Keane, J. M.; Harman, W. D. Organometallics 2005, 24, 1786− 1798. (13) Meiere, S. H.; Brooks, B. C.; Gunnoe, T. B.; Sabat, M.; Harman, W. D. Organometallics 2001, 20, 1038−1040. (14) Friedman, L. A.; You, F.; Sabat, M.; Harman, W. D. J. Am. Chem. Soc. 2003, 125, 14980−14981. (15) Meiere, S. H.; Valahovic, M. T.; Harman, W. D. J. Am. Chem. Soc. 2002, 124, 15099−15103. (16) Ding, F.; Valahovic, M. T.; Keane, J. M.; Anstey, M. R.; Sabat, M.; Trindle, C. O.; Harman, W. D. J. Org. Chem. 2004, 69, 2257−2267. (17) Graham, P. M.; Delafuente, D. A.; Liu, W.; Myers, W. H.; Sabat, M.; Harman, W. D. J. Am. Chem. Soc. 2005, 127, 10568−10572. K

DOI: 10.1021/acs.organomet.8b00027 Organometallics XXXX, XXX, XXX−XXX