Mechanistic Study of the Ru-catalyzed Asymmetric Hydrogenation of

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Mechanistic Study of the Ru-catalyzed Asymmetric Hydrogenation of Non-chelatable and Chelatable tert-Alkyl Ketones Using the Linear Tridentate spP/spNH/spN-combined Ligand PN(H)N: RuNH- and RuNK-involved Dual Catalytic Cycle 3

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Satoshi Nakane, Tomoya Yamamura, Sudipta Kumar Manna, Shinji Tanaka, and Masato Kitamura ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.8b02671 • Publication Date (Web): 16 Oct 2018 Downloaded from http://pubs.acs.org on October 16, 2018

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ACS Catalysis

Mechanistic Study of the Ru‐catalyzed Asymmetric Hydrogenation  of Non‐chelatable and Chelatable tert‐Alkyl Ketones Using the Line‐ ar Tridentate sp3P/sp3NH/sp2N‐combined Ligand PN(H)N: RuNH‐  and RuNK‐involved Dual Catalytic Cycle  Satoshi Nakane,† Tomoya Yamamura,‡ Sudipta Kumar Manna,† Shinji Tanaka,‡ Masato Kitamura*,† †Graduate School of Pharmaceutical Sciences, Nagoya University, Chikusa, Nagoya 464‐8601, Japan ‡

Graduate School of Science and Research Center for Materials Science, Nagoya University, Chikusa, Nagoya 464‐8602, Japan Supporting Information Placeholder

ABSTRACT: The linear tridentate sp3P/sp3NH/sp2N ligand PN(H)N ((R)‐2'‐(diphenylphosphino)‐N‐(pyridin‐2‐ ylmethyl)[1,1'‐binaphthalen]‐2‐amine) exclusively forms fac‐[Ru(PN(H)N)(dmso)3](BF4)2 over the mer isomer with the help of the three strongly ‐accepting DMSO ligands. The three different ligating atoms exert a divergent effect on the trans‐ DMSO–Ru bond strengths, enabling the stereoselective generation of fac‐RuH(CH3O)(PN(H)N)(dmso) (RuNH). RuNH effi‐ ciently hydrogenates both non‐chelatable t‐butyl methyl ketone (BMK) and chelatable t‐butyl methoxycarbonylmethyl ke‐ tone (BMCK) in the presence of a catalytic amount of CH3OK. The reaction proceeds at the H–sp3N‐‐‐Ru–H bifunctional re‐ action site of fac‐RuH2(PN(H)N)(dmso), and high enantioselectivity is attained in a chiral 3D cavity constructed by the sp3N‐ trans DMSO, the conformation of which is fixed by a PyC(6)H‐‐‐O=S hydrogen bond. We determined the structures of RuNH, the K amide RuNK, Ru dihydride, and Ru amido species by detailed NMR analysis using 15N‐labelled PN(H)N and C(3)‐Ph‐substituted PN(H)N. The rate of BMK hydrogenation is significantly affected by [CH3OK]0, showing a characteristic curve with a peak followed by a pseudo –1st‐order decay. The RuNH is easily deprotonated by CH3OK to generate RuNK, which is less reactive but has the same enantioface discrimination ability. Increased contribution of the slow RuNK cycle decreases the rate at higher [CH3OK]0. The RuNH‐ and RuNK‐involved dual catalytic cycle is supported by curve fitting analyses and K+ trapping experiments. In hydrogenation of BMCK, only the RuNH cycle operates because BMCK is preferen‐ tially deprotonated over RuNH. KEYWORDS: asymmetric catalysis, ketone hydrogenation, mechanism, NMR analysis, kinetic study, rate law analysis, base ef‐ fect commodated in the BINAP–Ru catalyst because the pseu‐ do‐equatorial phenyl groups on the phosphorous atoms stick out at the front.5 The protonated monodentate sim‐ ple ketone cannot be coordinated effectively to allow cap‐ ture and a move to the transition state (TS); this limits substrate generality to chelatable bidentate and sterically less demanding ketones. By contrast, in the BINAP–Ru/diamine system (Figure 1b), which operates under basic conditions, the –‐+‐–‐+ polarized H–Ru‐‐‐N–H moiety interacts with the polarized C=O group of the ketone substrate to increase the electro‐ philicity of the C=O carbon and facilitate hydride transfer to the C=O group. The intramolecular‐type DACat (Intra‐ mol‐DACat) mechanism of ketone hydrogenation has been extensively studied by Noyori,6,7 Morris,8 Bergens,9 Chen,10 Gordon,11 and Kitamura.12 Chelatable ketones, when pre‐ sent in large excess over the catalyst, replace the weakly coordinating diamine ligand, leading to loss of Intramol‐

1. INTRODUCTION   The leading concept of “soft transition metal/hard Brønsted acid combined catalyst” or “donor–acceptor bi‐ functional catalyst (DACat)”1,2 has led to two key BINAP– Ru methods. The BINAP–Ru/HCl catalyst was established in 1987 for the hydrogenation of chelatable functionalized ketones such as ‐keto esters.3 The BINAP–Ru/diamine ternary catalyst was developed in 1995 for non‐chelatable aromatic4a,b and sterically bulky unfunctionalized ke‐ tones.4c There is no omnipotent catalyst that can be ap‐ plied to both types of substrate. A possible explanation is shown in Figure 1. The BINAP–Ru/HCl combined catalyst captures a bidentate ‐keto ester, and the hydride (blue) on Ru is delivered to the carbonyl carbon, which is activat‐ ed by H+ (red) via an intermolecular‐type DACat (Intermol‐ DACat) mechanism (Figure 1a). ‐Keto esters with a ste‐ rically demanding tert‐alkyl group cannot be easily ac‐

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DACat ability and substrate inhibition. The degree of inhi‐ bition becomes more significant with a ‐keto ester be‐ cause the acidic  proton is easily deprotonated by the metal alkoxide required for activation of the Ru complex and generates the corresponding metal enolate, which has a stronger chelation ability. As a result, the usable sub‐ strates are limited to non‐chelatable simple ketones. Complementary use of the two BINAP–Ru methods co‐ vers

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ACS Catalysis mer isomer shows no reactivity under the same condi‐ tions.16 Here we have studied the mechanism underlying the DMSO

Figure 2. Asymmetric hydrogenation of non‐chelatable and chelatable tert‐alkyl ketones catalyzed by PN(H)N–Ru–DMSO complex 1.

effect in 1 responsible for the high performance catalysis, the origin of enantioselection, and the effect of the base and K+ ion on reactivity by means of i) structural analyses of the Ru complexes of the 15N‐labeled PN(H)N ligand and C(3)‐Ph‐substituted PN(H)N (Ph‐PN(H)N) by NMR; ii) a kinetic study and rate law analysis; iii) simulation coupled with curve fitting to the experimental observations of the base/rate relation; and iv) K+ trapping experiments using 2.2.2‐cryptand. The mechanisms of two hydrogenations employing 1 were studied under the standard conditions shown in Figure 3. The two hydrogenations included the conversion of non‐chelatable t‐butyl methyl ketone (BMK) to (S)‐t‐butyl methyl carbinol (BMC) (Figure 3a), and the conversion of t‐butyl methoxycarbonylmethyl ketone (BMCK) to (S)‐t‐butyl methoxycarbonylmethyl carbinol (BMCC) (Figure 3b). Both substrates are non‐aromatic ketones. Throughout this work, an R ligand was used; the suffix R is omitted in all cases.

Figure 1. Limitations of the two BINAP–Ru methods.

almost all types of ketonic substrate.13 However, a single catalyst suitable for both types of substrate is desirable. Such a catalyst system may be realized if dissociation of the diamine ligand from the ternary catalyst is avoided.14 With this idea in mind, we designed and synthesized (R)‐ BINAN‐Py‐PPh2 ((R)‐2'‐(diphenylphosphino)‐N‐(pyridin‐ 2‐ylmethyl)[1,1'‐binaphthalen]‐2‐amine (PN(H)N)), in which one of the PPh2 groups of BINAP is replaced with C(2)‐PyCH2NH (Figure 2).14 The non‐Pincer type PN(H)N tridentate ligand has the following characteristics: axial chirality; flexibility; a linearly arranged sp3P/sp3NH/sp2N combined system; and a single NH function that simplifies the reactive species, unlike the multi NH2 system in Figure 1b.15 A serious drawback, however, is that meridional (mer) and facial (fac) complexes are generated in the octa‐ hedral Ru complex, increasing the number of reactive spe‐ cies.16 Figure 2 shows the results of screening and optimi‐ zation of the conditions for the hydrogenation.17 Use of fac‐[Ru(PN(H)N)(dmso)3](BF4)2 (1) as a catalyst precursor has realized, for the first time, the asymmetric hydrogena‐ tion of both non‐chelatable and chelatable tert‐alkyl ke‐ tones, in a CH3OH–DMSO mixed solvent containing t‐BuOK, to furnish the corresponding secondary alcohol with the hydroxy group down when the structures are drawn as in Figure 2. The general rule for the enantioselection implies that the steric bulkiness of the ketone substrate, but not the functional group, is discriminated by the Ru hydride species derived from PN(H)N–Ru–DMSO complex 1. The fac geometry is important for attaining high reactivity; the

Figure 3. Standard conditions used for the mechanistic study of asymmetric hydrogenation of t‐butyl methyl ketone (BMK) and t‐butyl methoxycarbonylmethyl ketone (BMCK) using fac‐ [Ru(PN(H)N)(dmso)3](BF4)2 (1).16,17



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2. RESULTS AND DISCUSSION 

 8.43 31P:

2.1. Confirmation of Hydrogenation. 

–13.8

Ph2P

Deuterium labeling experiments confirmed that the reac‐ tion proceeds via hydrogenation but not transfer hydro‐ genation.18 Figure 4 shows that under H2/CD3OH condi‐ tions, a D atom was not introduced to the C=O carbon atom of either BMK or BMCK. The CH3OC(O) ester moiety of BMCK underwent exchange with CD3OH to form CD3OC(O).

31P:

H H N

Ph2P

N

H H

15N:

H

–13.1

N

H N

302

3

H H

 4.33, 4.92

PN(H)15N

PyC(6)H  9.17

H P

N

Ru

HS HR NH

 6.28

3

CDCl3

Ph-PN(H)N

CDCl3

C(8’)H—HS: 2.768 Å C(8')H  HS—C—N—H: 120.0°  HR—C—N—H: 7.4° HR

(BF4)2

HS

 4.33, 4.92

N H

 10.4 31P:

 3.54,  3.58

 binaphthyl : 70.4°

34.2

DMSO-d6

fac-[Ru(C6H6)(PN(H)N)](BF4)2 2

Figure 4. Incorporation of an H atom at the C=O carbon atom of BMK and BMCK. [BMK] = 1 M; [1] = 1 mM; [t‐BuOK] = 10 mM; [DMSO] = 1.4 M; CD3OH; 100 atm of H2; rt; 24 h. [BMCK] = 1 M; [1] = 1 mM; [t‐BuOK] = 20 mM; [DMSO] = 1.4 M; CD3OH; 100 atm of H2; rt; 24 h.

PyC(6)H 9.92

O

H P S

N Ru Cl

 2.22, 3.38



HS HR NH

4.144.98

N H

7.92 PyC(6)H

Cl 31P:

41.0 O

CDCl3

fac-RuCl2(Ph-PN(H)N)(dmso) 3

2.2.  Structural  Information  for  PN(H)N–  and  Ph‐PN(H)N– Ru Complexes.  

C(8’)H—HS: 2.685 Å C(8')H  HS—C—N—H: 108.5°  HR—C—N—H: 9.2° HS HR

Ru S

PyC(6)H—O: 2.639 Å Ru—S: 2.265 Å  N—Ru—S—O: 6.6°

 binaphthyl : 71.8°



Figure 5. Four key compounds used to determine the series of Ru complexes shown in Figures 6–8. The blue circle indicates 15N. 16,17

Figure 5 shows the four key compounds used for deduc‐ ing the structures of a series of Ru complexes that are pos‐ sibly related to the asymmetric hydrogenation. The first compound is the 15N‐Py‐incorporated PN(H)15N ligand (for its synthesis, see supporting information).18 The second compound is the C(3)‐Ph‐substituted PN(H)N ligand (Ph‐ PN(H)N).16 Introduction of the C(3)‐Ph group into the standard PN(H)N ligand can stabilize fac metal complexes because of steric repulsion between the C(3)‐Ph and C(2)‐ PyCH2NH groups in the mer geometry. The third and fourth compounds are, respectively, fac‐ [Ru(C6H6)(PN(H)N)]‐(BF4)2 (2)17 and fac‐RuCl2(Ph‐ PN(H)N)(dmso) (3),16 the structures of which have been definitively determined by X‐ray crystallographic anal‐ yses.16 The structures of non‐crystallizable Ru complexes obtained in sections 2.2.1.–2.2.4. were determined by comparing their NMR data to those of 2 and 3, with a focus on the

chemical shifts, coupling constants, and/or coupling pat‐ terns of PyCHSHRNH, PyC(6)H, DMSO, sp2N, and Ph2P units. These key NMR data of PN(H)N, Ph‐PN(H)N, 2, and 3 and the structural parameters of 2 and 3 in the corresponding crystals are shown in the chemical structures in Figure 5. In a similar way, the key NMR data of the Ru complexes are shown in Figures 6–8 to facilitate understanding the structural information. All the key NMR spectra were shown in supporting information (SI), and the section number was indicated for guidance: e.g. SI 5.1‐FS7–9 means that the detailed information is described in the Figures S7–S9 in section 5.1 of SI. 2.2.1.  fac‐Selective  Synthesis  [Ru(PN(H)15N)(dmso)3]‐(BF4)2 (1‐[15N]).  

of 

fac‐

Unlike geometrically restricted Pincer‐type tridentate linear ligands, the linear and flexible PN(H)N ligand has a serious disadvantage in that mer/fac stereoisomers may arise in the corresponding octahedral Ru complexes. Fur‐ thermore, the remaining three coordination sites are not identical, thereby causing further complexity in the con‐ struction of a reaction site. The highly fac‐selective formation of 1 was attained via a two‐step sequence (Figure 6). In the first step, PN(H)15N was arranged in a fac manner by using [Ru(C6H6)(CH3CN)3](BF4)2,19 which possesses 6‐arene as a fac‐specific ligand, and fac‐[Ru(C6H6)(PN(H)15N)](BF4)2 (2‐ [15N]) was formed quantitatively. Complex 2‐[15N] has a small JNP value of 5.2 Hz because of the cis sp3P/sp2N ar‐ rangement.20 As shown in Figure 5, the HS and HR atoms of PyCHSHRNH are located in very different environments: the HS–C–N–H and HR–C–N–H dihedral angles are 120.0° and 7.4°, respectively, and HS is proximal to the naphthalene

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ACS Catalysis fac structure and to realize the high‐performance hydro‐ genation in Figure 3 .

C(8')H (2.768 Å).17 The complex’s properties were similar in both crystalline and solution forms. The three H atoms of the PyCHSHRNH group showed an AMX‐type coupling pattern at δ 4.33 (HS, dd, J = 3.44 and 17.9 Hz (gem)), 4.92 (HR, dd, J = 8.95 and 17.9 Hz (gem)), and 10.4 (NH, dd, J = 3.44 and 8.95 Hz) in CDCl3; the two J values (3.44 Hz and 8.95 Hz) were consistent with those deduced by the Kar‐ plus rule (SI 5.1‐FS4).18 The nOe was also observed be‐ tween two hydrogen atoms, HS and C(8')H, that were spa‐ tially close.17,

2.2.2.  DMSO  Exchange  Rates  in  fac‐[Ru(PN(H)N] (dmso)3](BF4)2 (1).  The three DMSOs in fac‐[Ru(PN(H)N)(dmso)3](BF4)2 (1) are located trans to the three other ligating atoms,22 sp3P, sp3N, and sp2N, of PN(H)N, showing a different substitu‐ tion lability in the order of the trans effect (sp3N < sp2N < sp3P). The ‐accepting sp3P atom strengthens the P–Ru bond, resulting in significant replacement lability of the trans‐located DMSO. Regarding the sp3NH function, the ‐ donative lone pair electrons, in combination with hyper‐ conjugation of the N–H  orbital with the Ru d* orbital, raises the HOMO coefficient of the Ru d orbital to enhance its degree of interaction with the *S=O orbital of the sp3N‐ trans DMSO.21 The efficient dRu/*S=O overlap strengthens the Ru–DMSO coordinate bond. Furthermore, the PyC(6)H‐‐‐O=S(CH3)2 hydrogen bond will intensify the bonding strength. The sp2N‐trans DMSO is expected to have intermediate properties because the ‐acceptor strength of the Py sp2N atom is weaker than that of sp3P and its electron donicity is weaker than that of sp3N. The substitution lability of the three coordinating DMSOs was estimated by their exchange rate with DMSO‐d6 to be sp3P‐trans DMSO:sp2N‐trans DMSO:sp3N‐trans DMSO = ca. >37:2:1 (SI 5.2‐FS6–7).18 The significant difference among these groups is critical for realizing the high‐performance catalysis via stereoselective construction of the H–N‐‐‐Ru–H DACat reaction site (see section 2.2.3.).

Figure 6. Two‐step synthesis of fac‐ [Ru(PN(H)15N)(dmso)3](BF4)2 (1‐[15N]) via fac‐ [Ru(C6H6)(PN(H)15N)](BF4)2 (2‐[15N]) from [Ru(C6H6)(CH3CN)3](BF4)2 and PN(H)15N. For the molecular structure of 2 in crystal form, see Figure 5.

In the second step, the 6‐arene ligand in 2‐[15N] was re‐ placed with DMSO by gentle heating at 50 °C in DMSO for 48 h to quantitatively furnish 1‐[15N] containing a 3–5 mol amount of free DMSO ( 1.68 (C6D6)) after concentration. Complete removal of free DMSO was difficult even at 1 x 10–5 atm. At rt, 80% conversion of 2 to 1 was obtained after two weeks. Heating 2 at 100 °C for 30 min resulted in a complex mixture, indicating fragility of the tris‐DMSO complex 1. The fac geometry of 1‐[15N] was proven by the small JNP value, the AMX‐signal pattern of the PyCHSHRNH moiety of 1‐[15N], similarity to those of 2‐[15N] and fac‐ RuCl2(Ph‐PN(H)N)(dmso) (3), and ROESY analysis (SI 5.2‐ FS5 and ref 17). 18 A six‐membered hydrogen bond is formed between the DMSO oxygen atom and C(6)H of the Py moiety in the lig‐ and, as supported by the following: i) PyC(6)H resonates at  9.74, ca. 0.6 ppm lower than in the non‐DMSO complex 2; ii) in the molecular structure of 3 in the crystalline state (Figure 5),16 the PyC(6)H‐‐‐O=S distance is short (2.639 Å) and the sp2N‐‐‐Ru‐‐‐S=O dihedral angle is small (6.6°); and iii) PyC(6)H of 3 resonates at  9.92, close to that in 1‐[15N] ( 9.74). The fac stereochemistry was retained after re‐ placement of the benzene ligand with three DMSOs, as supported by the NMR behaviors of 1‐[15N], 2, and 3, to‐ gether with the molecular structures in crystalline 2 and 3. The trans arrangement of two DMSOs on Ru as O=S‐‐‐Ru‐‐‐ S=O is energetically disfavored;21 therefore, the fac coordi‐ nation is attained even with the linear and flexible PN(H)N ligand. Use of DMSO cosolvent is key to maintain the fragile

2.2.3.  Ru  Complexes  Derived  from  fac‐[Ru(PN(H)15N)‐ (dmso)3](BF4)2  (1‐[15N])  and  fac‐RuCl2(Ph‐PN(H)N)(dmso)  (3).   Figure 7 shows the step‐by‐step conversion of 1‐[15N] to fac‐RuH2(PN(H)15N)(dmso) (7‐[15N]), the proposed DACat reactive species in the present asymmetric hydrogenation (see sections 2.3.–2.6.). The structures of unstable com‐ plexes that are generated in‐situ were deduced by NMR analyses. Process 1 4  5. First, 1‐[15N] was quantitatively con‐ verted to a neutral Ru amido complex, fac‐ RuH(PN15N)(dmso)2 (4‐[15N]), in the presence of a 2 mol amount of t‐BuOK at rt in a 1:5 CH3OH–DMSO mixture, followed by concentration. One of two CH3OK molecules generated in situ from t‐BuOK and CH3OH sacrificially acts as a hydride donor by the liberation of formaldehyde and KBF4; another CH3OK or an intermediary Ru(OCH3)

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and quickly recovered the Ru amido complex 4 ( 54) (SI 5.4‐FS14,15).18 We believe that the Ru complex newly generated by the action of CH3OH on 4 is fac‐RuH(CH3O)(PN(H)N)(dmso) (5), although neither the Ru(OCH3) nor the NH signal could be detected (conditions: a 100 mol amount of CH3OH in C6D6). The exchange rate between Ru(OCH3) of 5 and free CH3OH may be very fast on the 1H‐NMR time scale, and 5 is thought to exist in equilibrium with a cationic Ru methox‐ ide anion complex 5'11 and a Ru amido/CH3OH complex 5"9a (Figure 7). The Ru(OCH3)/CH3OH exchange would be facilitated by the presence of a 3–5 mol amount of free DMSO via a DMSO coordinating 5'. As in the case of 1, complexes 4 and 5 are supposed to possess a PyC(6)H‐‐‐O=S hydrogen bond (PyC(6)H:  9.74 (1);  10.4 (4);  9.80 (5)) (SI 5.2‐FS5; 5.3‐FS8; 5.4‐FS14).18 Process 5  7. As shown in Figure 7 (see also Figure 10 in section 2.3.), the Ru methoxide complex 5 is most prob‐ able a precursor for the RuH2 complex fac‐ RuH2(PN(H)N)(dmso) (7), which is formed via the 2‐H2 complex 6. The 31P signal at  74 was, however, not changed by exposure of 5 to 1–50 atm of H2 in CH3OH con‐ taining a 0–1 mol amount of t‐BuOK at –78 °C and then at rt. Neither the RuH2 complex 7 nor the RuH(2‐H2) com‐ plex 6 was observed within the error of detection (SI 5.5‐ FS17,18),18 implying that the reactive complex 7 is ener‐ getically less stable than 5.12 The Ru methoxide 5 may be in the resting state or out of the catalytic loop. Immediate‐ ly after the generation of 7, the RuH2 species quickly reacts with a ketone substrate; in the absence of a ketone sub‐ strate, however, the RuH2 species may return to 5 via 6.12 Based on this assumption, aprotic conditions were adopted in accordance with the Morris’8b and Bergens’9b studies, in which a trans‐RuH2 species was detected in Noori’s BINAP–Ru/diamine system by 1H NMR. Exposure of fac‐RuH(PN15N)(dmso)2 (4‐[15N]) to 1 atm of H2 in THF‐ d8 at rt did not cause any reaction, whereas the addition of a 1 mol amount of t‐BuOK (–78 °C, 10 min; –60 °C, 1 h; rt, 30 min) furnished fac‐RuH2(PN(H)15N)‐ (dmso) (7‐[15N]) in 99% yield 1M 99:1 er R1, R2: unfunctionalized and/or functionalized alkyl

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ACS Catalysis

a t-butyl methyl ketone (BMK) 1 mM 1 10 mM t-BuOK

O +

H2

BMK 1M

OH

9:1 CH3OH–DMSO DMSO (1.4 M), rt BMC >99%, S:R = 98:2

50 atm

b t-butyl methoxycarbonylmethyl ketone (BMCK)

O

O

CH3O BMCK 500 mM

+

H2

1 mM 1 10 mM t-BuOK 9:1 CH3OH–DMSO DMSO (1.4 M), rt

50 atm

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O

OH

CH3O BMCC >99%, S:R = 99:1

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HO H >99% CH3

Page 22 of 37

O HO H

>99% CD3O

H H >99% >99% yield S:R = 99:1

ester exchange

>99% yield S:R = 98:2

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>99%

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ACS Catalysis

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(BF4)2

PN(H)15N

1.0 mol amt [Ru(C6H6)(CH3CN)3](BF4)2

δ 9.17

H P

δ 4.33, 4.92

N

Ru

NH

δ 10.4

CH3OH, rt, 30 min 15N:

2-[15N] 3–5 mol amt free DMSO (BF4)2 δ 9.74

O DMSO, 50 °C, 48 h

H P S

δ 4.28, 4.96

N

Ru

NH

δ 2.30, 3.18

amt: amount

δ 8.20

dmso dmso δ 3.03, 3.10

1-[15N]

δ 212 δ 34.2 2J NP = 5.2 Hz 31P:

δ 6.28

15N:

δ 214 δ 45.9 2J NP = 2.3 Hz 31P:

DMSO-d6

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DMSO-d6

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ACS Catalysis

3–5 mol amt free DMSO

3–5 mol amt free DMSO

(BF4)2 N

H P

δ 9.74

O

δ 4.28, 4.96

NH

Ru

S

δ 8.20

dmso dmso

15N:

δ 214 δ 45.3 2J NP = 2.3 Hz

δ 2.30, 3.18 δ 3.03, 3.10

2 mol amt t-BuOK N CH3OH δ 10.4 H P DMSO O Ru S conc. then C6D6 H δ 2.11, 3.58

31P:

1-[15N]

δ 2.85, 3.10

N

15N:

δ 265 δ 54.2 2J NP = 6.5 Hz

δ –13.4

31P:

2J

2 HN, JHP = 15, 17 Hz

DMSO-d6

conc. then C6D6

δ 2.20, 3.27

dmso

4-[15N]

CH3OH

C 6D 6

3–5 mol amt free DMSO δ 3.18, 3.57 δ 9.80

O

H P S

N

NH

Ru

O

OCH3

H

H P S

15N:

δ 2.24, 3.30

δ –13.8 2J , 2J HN HP = 17, 21 Hz

δ 271 δ 76.5 2J NP =