Regarding a Persisting Puzzle in Olefin Metathesis with Ru

Feb 3, 2016 - Regarding a Persisting Puzzle in Olefin Metathesis with Ru ... Catalysts for Olefin Metathesis: Anionic Ligand Exchange and Ease of Init...
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Regarding a Persisting Puzzle in Olefin Metathesis with Ru Complexes: Why are Transformations of Alkenes with a Small Substituent Z‑Selective? Sebastian Torker,* Ming Joo Koh, R. Kashif M. Khan, and Amir H. Hoveyda* Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467, United States S Supporting Information *

ABSTRACT: An enduring question in olefin metathesis is that reactions carried out with widely accessible Ru dichloro complexes, which typically favor E alkenes, generate Z isomers preferentially when substrates bearing a smaller substituent are used; Z enol ethers, alkenyl sulfides, 1,3-enynes, alkenyl halides, or alkenyl cyanides can be prepared reliably with reasonable efficiency and selectivity. Transformations thus proceed via the more hindered syn-substituted metallacyclobutanes, which is mystifying because catalyst features implemented in the more recently developed and broadly applicable Z-selective catalysts are absent in the Ru dichloro systems. Herein, we describe experimental and computational investigations that offer a plausible rationale for these puzzling selectivity trends. The following will be demonstrated. (1) Kinetic Z selectivity depends on the relative barrier for olefin association/dissociation versus metallacyclobutane formation/cleavage. There can be appreciable stereochemical control when metallacyclobutane formation/ breakage is turnover-limiting. (2) Stereoelectronicnot purely stericeffects are central: achieving the p-orbital overlap needed for alkene formation while minimizing steric repulsion between the incipient olefin substituent and a catalyst’s anionic ligand during the cycloreversion step is crucial. We show that similar stereoelectronic factors are probably operative in the more recently introduced Z-selective (and enantioselective) olefin metathesis transformations promoted by stereogenic-at-Ru complexes containing a bidentate aryloxide ligand.

1. INTRODUCTION A key recent advance in olefin metathesis1 is the development of catalysts that generate Z alkenes. The origin of the kinetic selectivity in different systems has been shown to be largely due to steric differentiation imposed by suitably disposed ligands that can differentiate between the two faces of the metallacyclobutane (mcb) plane (Scheme 1a).2 However, these advances occurred nearly 20 years before the recent examples of catalyst-controlled Z-selective olefin metathesis were reported (details below). Specifically, it was demonstrated that with alkenes containing a relatively small substituent, such as an alkyne, an alkoxy or aryloxy, a sulfide, or a halide, crossmetathesis (CM) and ring-opening/cross-metathesis (ROCM) processes reliably afford Z olefin products. What has been baffling is that these observations do not involve a specially designed catalyst (Scheme 1a)reactions were performed with the now commonly utilized Ru dichloro complexes (Scheme 1b). Despite the fact that these reactions have been known for two decades, a rationale for these observations has remained elusive. The heart of the problem is that reactions facilitated by Ru dichloro catalysts probably involve anti-to-phosphine or anti-to-NHC metallcyclobutane (mcb) intermediates3−5 where there is minimal steric differentiation (Scheme 1b). While there is a clear preference for E isomers with aryl- or alkyl-substituted substrates, which may be attributed to lowering of steric repulsion between the mcb substituents, it is difficult to explain © XXXX American Chemical Society

how and why a syn-substituted metallacycle would be preferred. The structural features that render syn-substituted mcb complexes favorable in the more recent kinetically Z-selective catalysts (Scheme 1a) do not exist in the Ru dichloro systems (Scheme 1b); the unexpected selectivities with the more traditional catalysts must therefore be due to other factors. A substrate’s diminutive substituents might lower the amounts of the E product formed but certainly not favor, and at times substantially, the higher energy Z isomer. There are several reasons why understanding the reason that Ru dichloro complexes promote kinetically controlled olefin metathesis is important. These reactions afford synthetically valuable organic molecules with commonly used and commercially available carbenes.6,7 What is more, attempts to design Z-selective olefin metathesis catalysts8 have led to structural alterations (i.e., replacement of one or both chloride ligands with alternative anionic units) with the loss of some of the prized attributes of the initial Ru dichloro complexes. For example, a species might contain a Ru−alkyl bond, rendering them unstable to aldehydes or carboxylic acids;9 others are constitutionally less stable and, at least in some circumstances, suffer from short life spans.9 In short, none of the more recently developed Z-selective catalysts offer the same substrate Received: November 25, 2015

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Scheme 1. A Longstanding Puzzle Regarding Olefin Metathesis Catalyzed by Ru Dichloro Complexes: Why Is There Selectivity Reversal with Alkenes That Contain a Relatively Small Substituent?

Scheme 2. Z-Selective Complexes Containing Differentiated Anionic Ligands and the Corresponding Favored Metallacyclobutane Intermediates

robustness and scope as before. A firmer grasp of the principles that cause a Ru dichloro complex to deliver high Z selectivity can be the key step toward development of more broadly

applicable stereoselective olefin metathesis catalysts. Additionally, mechanistic hypotheses that explain these unanticipated Z B

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Scheme 3. Unexpected Observations in Ring-Opening Cross-Metathesis: Why Are Reactions of Heteroatom-Substituted Alkenes Z-Selective?

Scheme 4. A Longstanding Mechanistic Issue: Why Are Cross-Metathesis Reactions of Alkenes That Have a Small Substituent and Are Promoted by Ru Dichloro Complexes Uncharacteristically Z-Selective?

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Organometallics Table 1. Stereoselectivity in ROCM of Oxabicycle 2 with Different Ru Complexes and Enol Ethersa

a Reactions performed under a N2 atmosphere. bConversion (based on the disappearance of 2) was determined by analysis of 400 MHz 1H NMR spectra of product mixtures prior to purification. cYield of products (±5%) after purification by silica gel chromatography. See the Supporting Information for details.

metathesis reactions involved Ru dichloro complexes and was revealed by Ozawa:19 high Z/E ratios were attained in an ROCM process performed with dichloride complex Ru-4a and an enol ether (1, Scheme 3a). These data are not consistent with thermodynamic ratios expected to favor the more stable Eβ-substituted enol ethers (∼65/35 E/Z).20 A more recent and similarly unexpected set of data relates to transformations with stereogenic-at-Ru carbene Ru-5b (Scheme 3a).21 Reactions with aryl- or alkyl-substituted α-alkenes, such as conversion of 2 to pyran 3, deliver E isomers with high selectivity (often 98/2 E/Z for 3). Depending on the cross partner, the sense of enantioselectivity is reversed as well. We have provided an explanation for the enantiomeric ratio (er) variations.22,23 The unforeseen Z selectivity, however, left us bewildered. The findings represented by those in Scheme 3a were surprising because, according to a steric model, appreciable Z selectivity would demand the involvement of energetically unfavorable mcb intermediates (vi or ix, Scheme 3b).15,16 Under such circumstances, the requisite syn-to-NHC approach of alkene substrates would bring about electron−electron and dipolar repulsion involving the polarized Ru−Cl bonds. Thus, if transformations proceed via trans-to-NHC (or phosphine) mcb species,4,5 then why would the reaction be channeled through a more sterically demanding syn-substituted metallacycle (i.e., vii or x vs viii or xi, respectively, Scheme 3b)? 2.3. Z-Selective CM with Dichloro Ru Complexes. Many Z-selective CM reactions catalyzed by a Ru dichloro complex have been reported (Scheme 4a). Among these are those with acrylonitrile24 and an enyne25 promoted by NHCRu complexes Ru-4b−d (5−7, Scheme 4a). Again, Z selectivities are distinct from what is expected on the basis of the thermodynamic product stability of β-substituted acrylonitriles (≥50/50 E/Z).26 There are instances relating to halogensubstituted olefins (8 and 9) generated by reactions with

selectivities can help us understand the surprising behavior of other types of catalysts. Herein, we detail studies that shed light on the basis for the high Z selectivity observed in olefin metathesis reactions promoted by Ru-based catalysts that typically favor the thermodynamically favored E isomers. We also provide a rationale for why stereogenic-at-Ru complexes, which furnish E ROCM products with aryl- or alkyl-substituted olefins, give Z olefins of the alternative enantiomers when enol ethers or vinyl sulfides are utilized.

2. BACKGROUND AND KEY QUESTIONS 2.1. Recent Development of Broadly Applicable ZSelective Olefin Metathesis Catalysts. The primary advance in catalyst-controlled Z-selective olefin metathesis arrived in the form of Mo-based monoaryloxide pyrrolide (MAP) complexes10 (e.g., Mo-1; Scheme 2). High stereoselectivity was achieved presumably due to preferential approach of the alkene trans to the pyrrolide ligand;11 the substituents within the mcb can then be oriented toward the smaller imido unit (vs the more sizable aryloxide; cf. i, Scheme 2). Related W species promote Z-selective ring-closing metathesis (RCM)12 or CM10c with unhindered olefins. ZSelective Ru carbenes were subsequently introduced. In the case of Ru-1,13 the incoming olefin may approach (cf. ii, Scheme 2) with the substituent oriented away from the larger N-heterocyclic carbene (NHC), giving rise to all-syn mcb intermediates.14 With Ru-2 it is a catechothiolate ligand15 that forces a metallacycle to be formed syn to the N-heterocyclic moiety, allowing steric effects to control the stereochemical outcome (via iii).16 A large sulfonate ligand has been shown to influence the Z/E ratio in ring-opening metathesis polymerization with phosphine-based Ru carbenes Ru-3a by favoring reaction through iv.17 Finally, thiolate complex Ru-3b has been employed in Z-selective homocoupling of α-olefins (via v).18 2.2. Z-Selective ROCM with Ru Dichloro and Halo Aryloxide Complexes. The first example of Z-selective olefin D

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Organometallics carbenes Ru-4e and Ru-4b.27 Although Z-1,2-disubstituted haloalkenes are slightly favored thermodynamically, the selectivities are too high for significant amounts of E-to-Z equilibration to be taking place.28 Finally, there is an indication that factors leading to kinetic Z selectivity in the types of CM processes represented above may be more general. As an example, in the reaction of allylbenzene and cis-1,4-diacetoxy-2butene E/Z ratios of ∼75/25 have been observed at low conversion (10, Scheme 4a), which is a Z content higher than that expected from thermodynamic product ratios (>87/13 E/ Z),29 which were attained only in the later stages of the process (>75% conversion).29 It has remained unclear why CM proceeds preferentially by means of a more congested synsubstituted mcb (xiii vs xiv, Scheme 4b).

origin of Z alkene formation when the phosphine-Ru complex is utilized. As will be shown, such trends are indicative of a change in turnover-limiting event, likely at the root of the stereoselectivity variations between reactions with Ru-4b and Ru-4f. 3.1.2. Olefin Coordination vs mcb Formation As the Stereochemistry-Determining Event: Origin of Stereoselectivity Variations. In this section, we analyze factors that give rise to Z/E variations (Table 1) observed with achiral Ru-4f vs phosphine-free Ru-4b. The rationale for the stereochemical preferences will be presented in the ensuing segment. The generally accepted principle that reactions involving Ru dichloro complexes such as Ru-4f and Ru-4b proceed through intermediates wherein the mcb is positioned anti to the sizable PCy3 or NHC ligand (cf. Scheme 3b) is supported by extensive experimental evidence.3−5 As such, the differences in the stereochemical outcome are not likely to be caused by steric effects induced by these large moieties (cf. Scheme 1). Kinetic studies in solution3a and in the gas phase3b demonstrate that a more strongly Lewis basic NHC allows the complex to react more quickly with alkenes (i.e., more favorable cycloaddition/ cycloreversion transition states).3d,g Further, the results in Table 1 are in line with experiments performed in the gas phase, which exhibit less pronounced substituent effects when the more reactive Ru complexes are involved (e.g., Ru-4b).31 Accordingly, whereas olefin coordination/dissociation steps may be rate determining with NHC-Ru systems (e.g., Ru-4b), mcb formation/cycloreversion is almost certainly turnover limiting when a phosphine-Ru species is present (e.g., Ru-4f). The relevance of distinctions in kinetic characteristics of the catalytic cycle (i.e., alkene association vs mcb formation as turnover limiting) to the changes in stereoselectivity (cf. Table 1) is illustrated in Figure 1. A more facile alkene binding, as with Ru-4b (red pathway), results in a more stable π complex (pc) followed by the formation of the derived mcb via ts1,

3. RESULTS AND DISCUSSION 3.1. Z-Selective Ring-Opening/Cross-Metathesis (ROCM) with Ru Dichloro Complexes. 3.1.1. Comparative Data Underscoring Chemo- and Stereoselectivity Preferences of Different Ru Dichloro Systems. Since there are not many cases of Z-selective ROCM with Ru dichloro systems (Scheme 3a), we first examined the performance of representative Ru complexes in the context of reactions with a collection of electronically altered aryl enol ethers (Table 1). Transformations with Ru-4f afforded enol ethers 11a−f in 59− 70% yield with appreciable Z selectivity (76/24−83/17 Z/E). When phosphine-free Ru-4b was used, reactions proceeded to >98% conversion (vs 62−94% for Ru-4f) and 11a−f were isolated in 58−63% yield. In contrast to ROCM with Ru-4f, the Z/E ratios correlated closely with the thermodynamic stability of product stereoisomers when Ru-4b was used (i.e., 40/60− 45/55 Z/E).20 Equally noteworthy is that the minimal stereochemical control in the ROCM processes with Ru-4b is unlike the CM examples shown in Scheme 4a, where NHC-Ru complexes deliver appreciable Z selectivity (up to >95/5 Z/E); this suggests a disparity in the energetics of the two types of transformations (see the discussion below). The analysis of efficiency (i.e., yield/conv values) in Table 1 indicates that, distinct from when Ru-4b is used, with Ru-4f, there is a dependence on the electronic attributes of the enol ether substituents. With Ru-4f conversion increased (62−94%) as the enol ether became more electron deficient, but with Ru4b there was complete consumption of the cyclic alkene regardless of the cross partner. The lower efficiencies with Ru4b (0.58−0.63) (vs Ru-4f (0.74−0.95)) are due to oligomerization of 2, which occurs to a greater extent with the NHC-Ru species involved. It is possible that all traces of kinetic Z selectivity disappear rapidly, as made evident by the swift Z-to-E equilibration (but without lowering of er) in the experiment performed with Ru4b (eq 1).22 However, in the case of dichloride carbene Ru-4b,

Figure 1. Depending on catalyst−substrate complex formation (14e → ts0 → pc) or mcb formation (pc → ts1 → mcb) being turnover limiting, an olefin metathesis reaction might be subject to kinetic control of stereoselectivity (schematic representation only). Abbreviations: 14e, 14-electron complex; ts, transition state; pc, π complex; mcb, metallacyclobutane.

after a relatively brief period (33% consumption of 2 after 1 h), there is no Z selectivity.30 Therefore, overall, comparison of the data obtained with Ru-4f and Ru-4b likely points to the kinetic E

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Organometallics which in turn is energetically more accessible than ts0. In consequence, with ts0 as the most elevated energy point involving a somewhat early transition state, different modes of olefin association become indistinguishable due to inherently longer Ru···C distances (∼3.5−4.0 Å in ts0) and diminished stereochemical control results. Conversely, the pre-equilibrium involving 14e and pc in the alternative scenario (blue pathway, representative of Ru-4f) may bring about appreciable kinetic stereoselectivity, since shorter Ru···C distances (∼2.0−2.5 Å) render steric factors more dominant and transformation via the less sterically encumbered intermediates becomes more favored. On account of similar mechanistic principles, we have demonstrated that Ru-catecholate species (irreversible formation of low-energy Ru−π complex (pc)) promote olefin metathesis nonselectively, whereas the processes with the corresponding catechothiolate system (turnover-limiting mcb generation) are highly Z selective (typically, 98/2 Z/E, Scheme 4a).27a 3.3.3. Homocoupling of Propene To Generate (E)- and (Z)2-Butene. Examination of CM between two aliphatic alkenes is M

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4. CONCLUSIONS The investigations described here provide a reason why Ru catalysts that promote reactions which are either E- or nonselective catalyze Z-selective olefin metathesis when the alkene substituent is relatively small. It is illustrated that the unexpected Z selectivities originate from stereoelectronic effects that affect the energetics of turnover-limiting mcb cleavage. This explanation is different from the largely steric factors that have been proposed for high Z/E ratios obtained in the recently developed Mo, W, and Ru systems. In summary, the following principles have emerged from the present study. (a) With olefin substrates bearing an alkoxy, a sulfide, a cyano, an alkynyl, or a halide, the role of steric factors that favor E product isomers (i.e., preference for intermediate transsubstituted mcb) is less important. This allows stereoelectronic effects to be in control. (b) Since reactions probably proceed via anti-to-phosphine or anti-to-NHC mcb complexes, steric interactions imposed by the Lewis basic ligands are not as significant. This is unlike the more recent Z-selective Ru-based as well as Mo- or W-based complexes. (c) In ROCM, the nature of the Lewis basic ligand of a Ru carbene (i.e., a monodentate phosphine or a monodentate NHC) determines whether catalyst−substrate association or mcb formation/cleavage is turnover limiting/stereochemistry determining. With a more strongly electron donating NHC, there is tighter alkene association (more Lewis acidic metal center and stronger back bonding),3d,g but in the case of phosphine−Ru systems the formation and cleavage of the metallacyclic intermediate is energetically most costly. (d) When olefin binding is turnover limiting in ROCM (i.e., with NHC-Ru complexes), because of the relatively long Ru···C distances, steric factors play a minimal role and kinetic control of stereochemistry becomes more challenging.32 This is not the same when transition states for mcb formation/cleavage represent the highest energy points; in such instances, a more intimate substrate−catalyst interaction means greater influence by steric factors and higher stereoselectivity. (e) Productive collapse of syn-substituted mcb is faster because achieving maximum overlap of the p orbitals that generate the product alkene is unhampered by steric repulsion between the catalyst’s chloride ligands and the substituents of the incipient olefin, which can therefore rotate in the same direction. With an anti-substituted mcb, to lower steric strain with the catalyst’s anionic ligands as the E alkene is being formed, the mcb substituents must move in the opposite direction, reducing overlap between the p orbitals of the incipient C−C double bond, rendering its formation more difficult. (f) Catalytic ROCM with enol ethers and vinyl sulfides, promoted by stereogenic-at-Ru complexes (e.g., Ru5b), are highly Z-selective since mcb cleavage is the stereochemistrydetermining step of the process. This is probably because of the added strain associated with the resulting spirocyclic mcb, courtesy of the bidentate chiral ligand. (g) In CM or homocoupling processes of terminal olefins catalyzed by “second-generation” Ru dichloro complexes that contain an NHC ligand, mcb cleavage is turnover limiting (vs olefin binding in ROCM). This may partially be because metallacycle cleavage releases a high-energy methylidene species. In consequence, the aforementioned stereoelectronic

effects control the stereochemical outcome and Z alkenes are favored. (h) The stereoelectronic effects described above likely apply to other olefin metathesis reactions, but their influence is masked with larger substrates where steric factors dominate (e.g., an aryl or an alkyl). As a result, anti-substituted mcb complexes that generate E product isomers become preferred. This investigation offers a new model for achieving high stereoselectivity in catalytic olefin metathesis. Thus, various other catalytic Z-selective reactions, designed to proceed through turnover limiting mcb cleavage, may be developed. The knowledge gained offers a deeper mechanistic understanding of one of the most important transformations in modern chemistry, facilitating future studies aimed at the development of more efficient and stereoselective catalysts.

5. EXPERIMENTAL SECTION 5.1. General Procedures. Unless otherwise noted, all reactions were performed with distilled and degassed solvents under an atmosphere of dry N2 in oven-dried (135 °C) or flame-dried glassware with standard drybox or vacuum-line techniques. Butyl vinyl ether (Aldrich), 2-chloroethyl vinyl ether (Aldrich), and cyclohexyl vinyl ether (Aldrich) were distilled from CaH2 under vacuum prior to use. Ru-4b (Aldrich), Ru-4f (Materia), cis-5-norbornene-exo-2,3-dicarboxylic anhydride (Aldrich), and 5-norbornene-2-exo,3-exo-dimethanol (Aldrich) were used as received. Ru-5a and Ru-5b were prepared according to a previously reported procedure.21d Oxabicyclic alkene 222 and N-tosyl-2,3-benzo-7-azabicyclo[2.2.1]hepta-2,5-diene16b were prepared in analogy to previously reported procedures. Enol ethers a−f were prepared according to previously published procedures and distilled from CaH2 under vacuum prior to use.52 Solvents (CH2Cl2, pentane, benzene) were purified under a positive pressure of dry Ar by a modified Innovative Technologies purification system. Tetrahydrofuran was distilled under a nitrogen atmosphere from Na/ benzophenone. All purification procedures of ROCM products were carried out with reagent grade solvents (purchased from Fisher) under benchtop conditions. Infrared (IR) spectra were recorded on a Bruker FTIR Alpha (ATR Mode) spectrometer, with νmax in cm−1. Bands are characterized as broad (br), strong (s), medium (m), or weak (w). 1H NMR spectra were recorded on a Varian Unity INOVA 400 (400 MHz) or a Varian Unity INOVA 500 (500 MHz) spectrometer. Chemical shifts are reported in ppm relative to tetramethylsilane with the solvent resonance resulting from incomplete deuterium incorporation as the internal standard (CDCl3: δ 7.26 ppm). Data are reported as follows: chemical shift, integration, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, br = broad, m = multiplet), and coupling constants (Hz). 13C NMR spectra were recorded on a Varian Unity INOVA 400 (100 MHz) or Varian Unity INOVA 500 (125 MHz) spectrometer with complete proton decoupling (denoted as 13C{1H}). Chemical shifts are reported in ppm from tetramethylsilane with the solvent resonance as the internal standard (CDCl3: δ 77.16 ppm). High-resolution mass spectrometry was performed on Micromass LCT ESI-MS and JEOL Accu TOF Dart (positive mode) instruments at the Boston College Mass Spectrometry Facility. Values for product Z/E ratios were determined by analysis of 1H NMR spectra. Enantiomeric ratios were determined by HPLC (Chiral Technologies Chiralpak OD-H, OJ-H, and OZ-H columns) in comparison with authentic N

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138.4, 129.1, 116.7, 115.7, 112.4, 76.3, 70.2, 68.1, 41.3, 40.7, 28.2, 15.9. HRMS: [M + H]+ calcd for C17H21O3 273.1491, found 273.1491. [α]D20.0 −55.4 (c = 0.36, CHCl3) for an enantiomerically enriched sample of 97/3 er. Enantiomeric purity was determined by HPLC analysis in comparison with authentic racemic material (Daicel Chiralpak OD-H column, 97/3 hexanes/i-PrOH, 0.5 mL/min, 220 nm). 5.2.3. (2R,4S,6S)-2-((Z)-2-Phenoxyvinyl)-6-vinyltetrahydro2H-pyran-4-ol (11c). Following the general procedure, a solution of Ru-5b (5.6 mg, 5.8 μmol, 5.0 mol %) in benzene (600 μL) was transferred by syringe to a vial containing oxabicyclic alkene 2 (15.0 mg, 0.119 mmol, 1.00 equiv) and enol ether c (286 mg, 2.38 mmol, 20.0 equiv). The resulting mixture was stirred for 12 h at 22 °C. Analysis of the unpurified mixture revealed 82% conversion of the substrate, and the ROCM product was obtained in a 93/7 Z/E ratio. The resulting brown oil was purified by silica gel chromatography (10% Et2O in hexanes to 50% Et2O in hexanes) to afford product 11c (21.7 mg, 0.0881 mmol, 74% yield) as a colorless oil. IR (CH2Cl2): 3368 (br), 2942 (w), 2919 (w), 2850 (w), 1675 (m), 1594 (m), 1489 (s), 927 (m). 1H NMR (400 MHz, CDCl3): Z isomer (major), δ 7.36−7.28 (2H, m), 7.11−7.04 (1H, m), 7.03−6.97 (2H, m), 6.40 (1H, dd, J = 6.2, 1.0 Hz), 5.90 (1H, ddd, J = 17.2, 10.5, 5.7 Hz), 5.28 (1H, dt, J = 17.3, 1.4 Hz), 5.14 (1H, dt, J = 10.6, 1.3 Hz), 4.96 (1H, dd, J = 8.0, 6.2 Hz), 4.62−4.50 (1H, m), 4.02−3.87 (2H, m), 2.10 (1H, ddt, J = 12.3, 4.4, 2.1 Hz), 2.03 (1H, ddt, J = 12.4, 4.3, 2.0 Hz), 1.45−1.23 (3H, m). 13C{1H} NMR (100 MHz, CDCl3): δ 157.3, 141.4, 138.4, 129.8, 123.2, 116.7, 115.7, 112.9, 76.3, 70.2, 68.0, 41.3, 40.7. HRMS: [M + H]+ calcd for C15H17O3 245.1178, found 245.1174. [α]D20.0 +104.0 (c = 0.48, CHCl3) for an enantiomerically enriched sample of 96/4 er. Enantiomeric purity was determined by HPLC analysis in comparison with authentic racemic material (Daicel Chiralpak OJ-H column, 95/5 hexanes/i-PrOH, 0.5 mL/min, 220 nm). 5.2.4. (2R,4S,6S)-2-((Z)-2-(4-Bromophenoxy)vinyl)-6-vinyltetrahydro-2H-pyran-4-ol (11d). Following the general procedure, a solution of Ru-5b (5.6 mg, 5.8 μmol, 5.0 mol %) in benzene (600 μL) was transferred by syringe to a vial containing oxabicyclic alkene 2 (15.0 mg, 0.119 mmol, 1.00 equiv) and enol ether d (473 mg, 2.38 mmol, 20.0 equiv). The mixture was stirred for 12 h at 22 °C. Analysis of the unpurified mixture revealed 90% conversion of the substrate, and the ROCM product was obtained in a 93/7 Z/E ratio. The resulting brown oil was purified by silica gel chromatography (10% Et2O in hexanes to 60% Et2O in hexanes) to afford product 11d (30.6 mg, 0.0941 mmol, 79% yield) as a colorless oil. IR (CH2Cl2): 3376 (br), 2918 (w), 2849 (w), 1674 (m), 1585 (m), 1483 (s), 924 (m), 820 (m); 1H NMR (400 MHz, CDCl3): Z isomer (major): δ 7.42 (2H, d, J = 8.9 Hz), 6.88 (2H, d, J = 9.0 Hz), 6.33 (1H, dd, J = 6.2, 1.0 Hz), 5.89 (1H, ddd, J = 17.3, 10.6, 5.7 Hz), 5.28 (1H, dt, J = 17.3, 1.4 Hz), 5.14 (1H, dt, J = 10.6, 1.3 Hz), 4.99 (1H, dd, J = 8.0, 6.2 Hz), 4.58− 4.41 (1H, m), 4.00−3.82 (2H, m), 2.11−2.00 (2H, m), 1.41− 1.24 (3H, m). 13C{1H} NMR (100 MHz, CDCl3): δ 156.3, 140.9, 138.3, 132.7, 118.5, 115.7, 115.7, 113.7, 76.3, 70.0, 68.0, 41.1, 40.7. HRMS: [M + Na]+ found for C15H17O3NaBr 347.0247. [α]D20.0 +69.9 (c = 1.0, CHCl3) for an enantiomerically enriched sample of 96/4 er. Enantiomeric purity was determined by HPLC analysis in comparison with authentic racemic material (Daicel Chiralpak OD-H column, 97/3 hexanes/i-PrOH, 0.5 mL/min, 220 nm).

racemic materials. Optical rotations were measured on a Rudolph Research Analytical Autopol IV Polarimeter. 5.2. General Procedure for ROCM. In an N2-filled glovebox, an oven-dried 4 mL vial equipped with a magnetic stir bar was charged with the strained cyclic alkene (1.0 equiv) and the terminal olefin cross partner (20 equiv). In this vial, a solution of catalyst (Ru-4b, Ru-4f, Ru-5a, or Ru-5b; 5.0 mol %) in benzene/tetrahydrofuran was placed. The resulting mixture was stirred for 4−24 h at 22 °C, after which the reaction was concentrated in vacuo (percent conversion determined by 400 or 500 MHz 1H NMR analysis). Purification was performed through silica gel chromatography. 5.2.1. (2R,4S,6S)-2-((Z)-2-(4-Butoxyphenoxy)vinyl)-6-vinyltetrahydro-2H-pyran-4-ol (11a). Following the general procedure for ROCM, a solution of Ru-5b (5.6 mg, 5.8 μmol, 5.0 mol %) in benzene (600 μL) was transferred by syringe to a vial containing oxabicyclic alkene 2 (15.0 mg, 0.119 mmol, 1.00 equiv) and enol ether a (457 mg, 2.38 mmol, 20.0 equiv). The resulting mixture was stirred for 12 h at 22 °C. Analysis of the unpurified mixture indicated substrate 66% conversion, and the product was obtained in 92/8 Z/E ratio. The resulting brown oil was purified by silica gel chromatography (10% Et2O in hexanes to 50% Et2O in hexanes) to afford 11a (24.3 mg, 0.0763 mmol, 64% yield) as a colorless oil. IR (CH2Cl2): 3383 (br), 2936 (w), 2871 (w), 1674 (w), 1502 (s), 826 (m). 1H NMR (400 MHz, CDCl3): Z isomer (major), δ 6.92 (2H, d, J = 9.1 Hz), 6.83 (2H, d, J = 9.1 Hz), 6.31 (1H, dd, J = 6.2, 1.0 Hz), 5.90 (1H, ddd, J = 17.3, 10.6, 5.7 Hz), 5.28 (1H, dt, J = 17.3, 1.4 Hz), 5.14 (1H, dt, J = 10.6, 1.3 Hz), 4.87 (1H, dd, J = 8.0, 6.2 Hz), 4.54 (1H, dddd, J = 11.2, 8.0, 2.0, 1.0 Hz), 3.97−3.89 (4H, m), 2.10 (1H, ddt, J = 12.3, 4.4, 2.1 Hz), 2.03 (1H, ddt, J = 12.3, 4.3, 2.1 Hz), 1.79−1.70 (2H, m), 1.53− 1.43 (2H, m), 1.43−1.24 (3H, m), 0.97 (3H, t, J = 7.4 Hz). 13 C{1H} NMR (100 MHz, CDCl3): δ 155.3, 151.3, 142.6, 138.4, 117.9, 115.7, 115.5, 111.7, 76.3, 70.1, 68.4, 68.1, 41.3, 40.7, 31.5, 19.4, 14.0. HRMS: [M + H]+ calcd for C19H26O4 318.1831, found 318.1847. [α]D20.0 +12.8 (c = 0.48, CHCl3) for an enantiomerically enriched sample of 97/3 er. Enantiomeric purity was determined by HPLC analysis in comparison with authentic racemic material (Daicel Chiralpak OD-H column, 97/3 hexanes/i-PrOH, 0.5 mL/min, 220 nm). 5.2.2. (2R,4S,6S)-2-((Z)-2-(4-Ethylphenoxy)vinyl)-6-vinyltetrahydro-2H-pyran-4-ol (11b). Following the general procedure, a solution of Ru-5b (5.6 mg, 5.8 μmol, 5.0 mol %) in benzene (600 μL) was transferred by syringe to a vial containing oxabicyclic alkene 2 (15.0 mg, 0.119 mmol, 1.00 equiv) and enol ether b (352 mg, 2.38 mmol, 20.0 equiv). The resulting mixture was stirred for 12 h at 22 °C. Analysis of the unpurified mixture revealed 74% conversion of the substrate, and the ROCM product was obtained in a 91/9 Z/E ratio. The resulting brown oil was purified by silica gel chromatography (10% Et2O in hexanes to 50% Et2O in hexanes) to afford product 11b (22.5 mg, 0.0820 mmol, 69% yield) as a colorless oil. IR (CH2Cl2): 3375 (br), 2962 (w), 2920 (w), 2850 (w), 1674 (m), 1606 (w), 1506(s), 925 (m), 829 (m). 1H NMR (400 MHz, CDCl3): Z isomer (major), δ 7.14 (2H, d, J = 8.7 Hz), 6.92 (2H, d, J = 8.6 Hz), 6.37 (1H, dd, J = 6.2, 1.1 Hz), 5.90 (1H, ddd, J = 17.3, 10.6, 5.7 Hz), 5.28 (1H, dt, J = 17.3, 1.4 Hz), 5.14 (1H, dt, J = 10.6, 1.3 Hz), 4.92 (1H, dd, J = 8.0, 6.2 Hz), 4.64−4.44 (1H, m), 4.01−3.86 (2H, m), 2.61 (2H, q, J = 7.6 Hz), 2.10 (1H, ddt, J = 12.2, 4.2, 2.0 Hz), 2.03 (1H, ddt, J = 12.3, 4.3, 2.0 Hz), 1.41−1.25 (3H, m), 1.21 (3H, t, J = 7.6 Hz). 13C{1H} NMR (100 MHz, CDCl3): δ 155.4, 141.9, 139.2, O

DOI: 10.1021/acs.organomet.5b00970 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics 5.2.5. (2R,4S,6S)-2-((Z)-2-(4-Chlorophenoxy)vinyl)-6-vinyltetrahydro-2H-pyran-4-ol (11e). Following the general procedure, a solution of Ru-5b (5.6 mg, 5.8 μmol, 5.0 mol %) in benzene (600 μL) was transferred by syringe to a vial containing oxabicyclic alkene 2 (15.0 mg, 0.119 mmol, 1.00 equiv) and enol ether e (368 mg, 2.38 mmol, 20.0 equiv). The resulting mixture was stirred for 12 h at 22 °C. Analysis of the unpurified mixture revealed 93% conversion of the substrate, and the ROCM product was obtained in 93/7 Z/E ratio. The resulting brown oil was purified by silica gel chromatography (10% Et2O in hexanes to 60% Et2O in hexanes) to afford 11e (25.0 mg, 0.0890 mmol, 75% yield) as a colorless oil. IR (CH2Cl2): 3374 (br), 2942 (w), 2918 (w), 2949 (w) 1675 (m), 1592 (m), 1486 (s), 926 (m), 823 (m). 1H NMR (400 MHz, CDCl3): Z isomer (major), δ 7.27 (2H, d, J = 9.0 Hz), 6.93 (2H, d, J = 8.9 Hz), 6.33 (1H, d, J = 6.2 Hz), 5.89 (1H, ddd, J = 16.2, 10.5, 5.7 Hz), 5.28 (1H, dt, J = 17.3, 1.4 Hz), 5.14 (1H, dt, J = 10.6, 1.3 Hz), 4.98 (1H, dd, J = 7.9, 6.3 Hz), 4.57−4.46 (1H, m), 4.01−3.83 (2H, m), 2.14−1.98 (2H, m), 1.41−1.21 (3H, m). 13C{1H} NMR (100 MHz, CDCl3): δ 155.8, 141.1, 138.3, 1298, 128.3, 118.0, 115.7, 113.6, 76.3 70.1, 68.0, 41.2, 40.7. HRMS: [M + Na]+ found for C15H17O3NaCl 303.0749. [α]D20.0 +103.2 (c = 0.58, CHCl3) for an enantiomerically enriched sample of 95/5 er. Enantiomeric purity was determined by HPLC analysis in comparison with authentic racemic material (Daicel Chiralpak OD-H column, 97/3 hexanes/i-PrOH, 0.5 mL/min, 220 nm). 5.2.6. (2R,4S,6S)-2-((Z)-2-(4-(Trifluoromethyl)phenoxy)vinyl)-6-vinyltetrahydro-2H-pyran-4-ol (11f). Following the general procedure, a solution of Ru-5b (5.6 mg, 5.8 μmol, 5.0 mol %) in benzene (600 μL) was transferred by syringe to a vial containing oxabicyclic alkene 2 (15.0 mg, 0.119 mmol, 1.00 equiv) and enol ether f (447 mg, 2.38 mmol, 20.0 equiv). The resulting mixture was stirred for 12 h at 22 °C. Analysis of the unpurified mixture revealed 95% conversion of the substrate, and the ROCM product was obtained in a 93/7 Z/E ratio. The resulting brown oil was purified by silica gel chromatography (10% Et2O in hexanes to 60% Et2O in hexanes) to afford 11f (27.3 mg, 0.0869 mmol, 73% yield) as a colorless oil. IR (CH2Cl2): 3374 (br), 2922 (w), 2852 (w), 2949 (w) 1677 (w), 1613 (m), 1515 (m), 929 (m), 837 (m). 1H NMR (400 MHz, CDCl3): Z isomer (major), δ 7.59 (2H, d, J = 8.8 Hz), 7.08 (2H, d, J = 8.7 Hz), 6.41 (1H, dd, J = 6.2, 1.1 Hz), 5.89 (1H, ddd, J = 17.3, 10.6, 5.7 Hz), 5.28 (1H, dt, J = 17.3, 1.4 Hz), 5.15 (1H, dt, J = 10.6, 1.3 Hz), 5.08 (1H, dd, J = 8.2, 6.2 Hz), 4.63− 4.47 (1H, m), 4.03−3.83 (2H, m), 2.11−2.00 (2H, m), 1.40− 1.28 (3H, m). 13C{1H} NMR (100 MHz, CDCl3): δ 140.1, 138.2, 127.3, 127.3, 116.6, 115.8, 114.9, 76.4, 70.0, 68.0, 41.1, 40.7, 29.9. HRMS: [M + Na]+ found for C16H17O3NaF3 337.1017. [α]D20.0 −10.5 (c = 0.95, CHCl3) for an enantiomerically enriched sample of 96/4 er. Enantiomeric purity was determined by HPLC analysis in comparison with authentic racemic material (Daicel Chiralpak OD-H column, 97/3 hexanes/i-PrOH, 0.5 mL/min, 220 nm). 5.2.7. (3aS,4S,6R,6aR)-4-((Z)-2-Butoxyvinyl)-6-vinyltetrahydro-1H-cyclopenta[c]furan-1,3(3aH)-dione (12). Following the general procedure, a solution of Ru-5b (4.4 mg, 4.6 μmol, 5.0 mol %) in benzene (460 μL) was transferred by syringe to a vial containing cis-5-norbornene-exo-2,3-dicarboxylic anhydride (15.0 mg, 0.0914 mmol, 1.00 equiv) and butyl vinyl ether (183 mg, 1.83 mmol, 20.0 equiv). The resulting mixture was stirred for 4 h at 22 °C. Analysis of the unpurified mixture showed >98% conversion of the substrate, and the ROCM product was

obtained in an 81/19 Z/E ratio. The resulting brown oil was purified by silica gel chromatography (10% Et2O in hexanes to 20% Et2O in hexanes) to afford 12 (19.3 mg, 0.0730 mmol, 80% yield) as a colorless oil. IR (CH2Cl2): 2959 (w), 2944 (m), 2929 (w), 2872 (w), 1857 (w), 1778 (s), 1664 (w). 1H NMR (500 MHz, CDCl3): Z isomer (major), δ 6.06 (1H, d, J = 6.2 Hz), 5.88 (1H, ddd, J = 17.2, 10.3, 7.0 Hz), 5.22 (1H, dd, J = 17.1, 1.0 Hz), 5.14 (1H, dd, J = 10.3, 1.0 Hz), 4.43−4.32 (1H, m), 3.76 (2H, t, J = 6.6 Hz), 3.29−3.22 (2H, m), 2.99−2.84 (1H, m), 2.25−2.13 (1H, m), 1.62−1.54 (4H, m), 1.41−1.33 (2H, m), 0.93 (3H, t, J = 7.4 Hz). 13C{1H} NMR (100 MHz, CDCl3): δ 172.7, 172.0, 147.5, 137.8, 116.4, 105.0, 72.5, 52.1, 51.2, 47.8, 42.4, 40.1, 31.7, 18.9, 13.7. HRMS: [M + H]+ calcd for C15H21O4 265.1440, found 265.1448. [α]D20.0 −16.4 (c = 0.61, CHCl3) for an enantiomerically enriched sample of 80/20 er. Enantiomeric purity was determined by HPLC analysis in comparison with authentic racemic material (Daicel Chiralpak OD−H column, 97/3 hexanes/i-PrOH, 0.5 mL/min, 220 nm). 5.2.8. (1R,2S,3R,5R)-3-((Z)-2-Butoxyvinyl)-5-vinylcyclopentane-1,2-diyl)dimethanol (13). Following the general procedure, a solution of Ru-5a (4.2 mg, 4.9 μmol, 5.0 mol %) in tetrahydrofuran (490 μL) was transferred by syringe to a vial containing 5-norbornene-2-exo,3-exo-dimethanol (15.0 mg, 0.0973 mmol, 1.00 equiv) and butyl vinyl ether (195 mg, 1.95 mmol, 20.0 equiv). The solution was stirred for 4 h at 22 °C. Analysis of the unpurified mixture revealed >98% conversion of the substrate, and the ROCM product was obtained in a 94/6 Z/E ratio. The resulting brown oil was purified by silica gel chromatography (20% Et2O in hexanes to 70% Et2O in hexanes) to afford 13 (21.3 mg, 0.0837 mmol, 86% yield) as a colorless oil. The spectral data for this compound were identical with those reported in the literature.16b [α]D20.0 +54.0 (c = 0.37, CHCl3) for an enantiomerically enriched sample of 81/19 er. Enantiomeric purity was determined by HPLC analysis in comparison with authentic racemic material (Daicel Chiralpak OD-H column, 97/3 hexanes/i-PrOH, 0.5 mL/min, 220 nm). 5.2.9. (1S,3R)-1-((Z)-2-Butoxyvinyl)-2-tosyl-3-vinylisoindoline (14a). Complex Ru-5b (4.3 mg, 4.5 μmol, 5.0 mol %) was placed in a vial containing N-tosyl-2,3-benzo-7-azabicyclo[2.2.1]hepta-2,5-diene (15.0 mg, 0.0504 mmol, 1.00 equiv) and butyl vinyl ether (101 mg, 1.01 mmol, 20.0 equiv). The resulting mixture was stirred for 4 h at 22 °C. Analysis of the unpurified mixture revealed >98% conversion of the substrate, and the ROCM product was obtained in a 95/5 Z/E ratio. The resulting brown oil was purified by silica gel chromatography (10% Et2O in hexanes to 40% Et2O in hexanes) to afford product 14a (18.0 mg, 0.0453 mmol, 90% yield) as a colorless oil. The spectral data for this compound were identical with those reported in the literature.16b [α]D20.0 −14.9 (c = 0.67, CHCl3) for an enantiomerically enriched sample of 93/7 er. Enantiomeric purity was determined by HPLC analysis in comparison with authentic racemic material (Daicel Chiralpak OZ-H column, 97/3 hexanes/i-PrOH, 0.5 mL/min, 220 nm). 5.2.10. (1S,3R)-1-((Z)-2-(2-Chloroethoxy)vinyl)-2-tosyl-3-vinylisoindoline (14b). Complex Ru-5b (4.3 mg, 4.5 μmol, 5.0 mol %) was placed in a vial containing N-tosyl-2,3-benzo-7azabicyclo[2.2.1]hepta-2,5-diene (15.0 mg, 0.0504 mmol, 1.00 equiv) and 2-chloroethyl vinyl ether (107 mg, 1.01 mmol, 20.0 equiv). The resulting mixture was stirred for 4 h at 22 °C. Analysis of the unpurified mixture showed >98% conversion of the substrate, and the ROCM product was obtained in a >98/2 Z/E ratio. The resulting brown oil was purified by silica gel P

DOI: 10.1021/acs.organomet.5b00970 Organometallics XXXX, XXX, XXX−XXX

Article

Organometallics

optimized with two different functionals: BP8655 and ωB97XD.39c Single-point electronic energy (ΔEsp) calculations applying functionals BP86, ωB97XD, and M0639b in solution (benzene and dichloromethane) were performed on the gasphase geometries obtained with basis1 through application of an integral equation formalism variant of the polarizable continuum model (IEFPCM)56 and the larger basis set termed “basis2”: 6-311+G(2d,p) on H, C, O, N, P, and Cl and MWB28/MWB46 on ruthenium and iodide. The single-point electronic energies (ΔEsp) at the basis2 level were corrected by addition of thermal corrections to the Gibbs free energy (ΔGcorr) obtained at the corresponding basis1 level. In addition, we have investigated the relationship between ts0 and ts2 in more detail. Therefore, we have reoptimized the potential energy surfaces in Figure 3 with BP86/basis1 in dichloromethane and performed single-point calculations with BP86D3BJ and PBE0-D3BJ57 (both of which include Grimme’s D3 empirical dispersion with Becke-Johnson damping),41a as well as with ωB97XD and M06 with the even larger Def2QZVP58 basis set.42

chromatography (10% Et2O in hexanes to 40% Et2O in hexanes) to afford 14b (18.9 mg, 0.0468 mmol, 93% yield) as a colorless oil. IR (CH2Cl2): 2922 (w), 1665 (m), 1598 (w), 1459 (w), 1348 (m), 1164 (s), 1094 (m), 1048 (m), 576 (m), 551 (m). 1H NMR (400 MHz, CDCl3): Z isomer (major), δ 7.81 (2H, d, J = 8.3 Hz), 7.29−7.27 (1H, m), 7.26−7.19 (3H, m), 7.18−7.13 (1H, m), 7.07−7.01 (1H, m), 6.17 (1H, dd, J = 6.0, 1.1 Hz), 5.99−5.87 (2H, m), 5.41 (1H, dt, J = 17.0, 1.1 Hz), 5.25 (1H, d, J = 7.3 Hz), 5.22 (1H, dt, J = 10.0, 1.2 Hz), 4.68 (1H, dd, J = 8.9, 6.0 Hz), 4.21−4.07 (2H, m), 3.83−3.72 (2H, m), 2.38 (3H, s). 13C{1H} NMR (100 MHz, CDCl3): δ 145.6, 143.5, 139.6, 139.5, 137.8, 135.5, 129.7, 128.4, 128.0, 128.0, 123.5, 123.2, 116.3, 111.0, 72.6, 68.5, 60.7, 42.8, 21.7. HRMS: [M + H]+ calcd for C21H23ClNO3S 404.1087, found 404.1107. [α]D20.0 +32.7 (c = 0.61, CHCl3) for an enantiomerically enriched sample of 97/3 er. Enantiomeric purity was determined by HPLC analysis in comparison with authentic racemic material (Daicel Chiralpak OZ-H column, 95/5 hexanes/i-PrOH, 0.5 mL/min, 220 nm). 5.2.11. (1S,3R)-1-((Z)-2-(Cyclohexyloxy)vinyl)-2-tosyl-3-vinylisoindoline (14c). Following the general procedure, a solution of Ru-5b (4.3 mg, 4.5 μmol, 5.0 mol %) in tetrahydrofuran (250 μL) was transferred by syringe to a vial containing N-tosyl-2,3-benzo-7-azabicyclo[2.2.1]hepta-2,5diene (15.0 mg, 0.0504 mmol, 1.00 equiv) and cyclohexyl vinyl ether (127 mg, 1.01 mmol, 20.0 equiv). The resulting mixture was stirred for 4 h at 22 °C. Analysis of the unpurified mixture indicated >98% conversion of the substrate, and the product was obtained in a 95/5 Z/E ratio. The resulting brown oil was purified by silica gel chromatography (10% Et2O in hexanes to 40% Et2O in hexanes) to afford 14c (19.9 mg, 0.0470 mmol, 93% yield) as a colorless oil. IR (CH2Cl2): 2930 (m), 2856 (w), 1664 (m), 1598 (w), 1450 (w), 1342 (m), 1162 (s), 1094 (s), 1043 (s), 576 (s), 550 (s). 1H NMR (400 MHz, CDCl3): Z isomer (major), δ 7.82 (2H, d, J = 8.3 Hz), 7.27− 7.24 (2H, m), 7.24−7.19 (2H, m), 7.17−7.11 (1H, m), 7.07− 7.02 (1H, m), 6.22 (1H, dd, J = 6.1, 1.0 Hz), 5.95 (1H, ddd, J = 17.5, 10.0, 7.5 Hz), 5.85 (1H, d, J = 8.9 Hz), 5.42 (1H, dd, J = 17.0, 1.0 Hz), 5.28 (1H, d, J = 7.5 Hz), 5.22 (1H, dd, J = 10.0, 0.9 Hz), 4.57 (1H, dd, J = 8.9, 6.1 Hz), 3.81−3.73 (1H, m), 2.39 (3H, s), 2.05−1.90 (2H, m), 1.88−1.74 (2H, m), 1.65− 1.48 (4H, m), 1.39−1.33 (2H, m). 13C{1H} NMR (100 MHz, CDCl3): δ 145.2, 143.3, 140.3, 139.7, 137.7, 135.6, 129.6, 128.3, 128.2, 127.8, 123.5, 123.2, 116.1, 108.9, 80.1, 68.5, 61.0, 32.6, 35.7, 25.7, 23.7, 21.7. HRMS: [M + H]+ calcd for C25H30NO3S 424.1946, found 424.1956. [α]D20.0 −66.5 (c = 0.60, CHCl3) for an enantiomerically enriched sample of 94/6 er. Enantiomeric purity was determined by HPLC analysis in comparison with authentic racemic material (Daicel Chiralpak OZ-H column, 95/5 hexanes/i-PrOH, 0.5 mL/min, 220 nm). 5.3. Computational Methods. DFT37 computations were performed with the Gaussian 09 suite of programs.53 The following basis set (termed “basis1”) was used for geometry optimizations and evaluation of thermal corrections to the Gibbs free energy under standard conditions (298.15 K, 1 atm): 6-31G(d,p) basis set for hydrogen and carbon atoms, including additional diffuse functions (+) on heteroatoms (oxygen, nitrogen, phosphorus and chloride). A quasi-relativistic effective core potential (ECP) of the Stuttgart−Dresden type54 was used for ruthenium and iodide (MWB28 and MWB46 keywords, respectively, in Gaussian for basis set and ECP). The nature of all stationary points was checked through vibrational analysis. Geometries for the potential energy surfaces have been

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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/acs.organomet.5b00970. Spectral data for products (1H and 13C NMR, HPLC chromatograms) and electronic and Gibbs free energies and energy diagrams with various density functionals (BP86, ω-B97XD, M06, BP86-D3BJ, and PBE0-D3BJ) in the gas phase and solution (PDF) Computed molecule Cartesian coordinates (XYZ)

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AUTHOR INFORMATION

Corresponding Authors

*E-mail for S.T.: [email protected]. *E-mail for A.H.H.: [email protected]. Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS Financial support was provided by the NSF (CHE-1362763) and AstraZeneca (fellowship to R.K.M.K.). We thank Boston College Research Services for access to computational facilities.

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