Ti-Salan catalyzed asymmetric sulfoxidation of pyridylmethylthiobenzimidazoles to optically pure proton pump inhibitors

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Ti-Salan catalyzed asymmetric sulfoxidation of pyridylmethylthiobenzimidazoles to optically pure proton pump inhibitors Evgenii P. Talsi a,b , Konstantin P. Bryliakov a,b,∗ a b

Novosibirsk State University, Pirogova 2, Novosibirsk 630090, Russia Boreskov Institute of Catalysis, Pr. Lavrentieva 5, Novosibirsk 630090, Russia

a r t i c l e

i n f o

Article history: Received 15 October 2015 Received in revised form 10 March 2016 Accepted 14 March 2016 Available online xxx Keywords: Asymmetric oxidation Esomeprazole Hydrogen peroxide Isoinversion Mechanism Titanium Salan

a b s t r a c t The asymmetric sulfoxidation of two pyridylmethylthiobenzimidazoles to anti-ulcer drugs of the PPI family (S)-omeprazole and (R)-lansoprazole with hydrogen peroxide, mediated by a series of chiral titanium(IV) salan complexes is reported. High sulfoxide yields (up to >95%) and enantioselectivities (up to 94% ee) have been achieved. The introduction of electron-withdrawing substituents leads to less active and less enantioselective catalysts. Like for the previously reported Ti-salalen catalyzed sulfoxidations, the temperature dependence of the sulfoxidation enantioselectivity in the presence of Ti-salan complexes is nonmonotonic, demonstrating isoinversion behavior with decreasing temperature. The oxidation is likely rate-limited by the formation of the active (presumably peroxotitanium(IV)) species, followed by a faster oxygen transfer to the substrate. © 2016 Elsevier B.V. All rights reserved.

1. Introduction After the milestone emergence of the Kagan-Modena catalyst system, capable of conducting the highly enantioselective oxidation of thioethers to sulfoxides with alkylhydroperoxides [1–3], transition-metal catalyzed sulfoxidations have made a substantial progress [4–16], with one of the major trends being the development of environmentally benign catalyst systems relying on “green” hydrogen peroxide as the terminal oxidant [17–27]. In spite of extensive studies, some drawbacks persisted, i.e., until recently there were no simple and highly enantioselective catalyst systems able to oxidize thioethers, bearing two bulky substituents at the sulfur atom, with H2 O2 . From a practical perspective, simple, efficient and environmentally benign catalyst systems are highly challenging. At the moment, the industry continues exploiting the Kagan-Modena type systems possessing serious technical and environmental drawbacks [28]. In particular, the blockbuster anti-ulcer drug (S)-

∗ Corresponding author at: Boreskov Institute of Catalysis, Pr. Lavrentieva 5, Novosibirsk 630090, Russia, and Novosibirsk State University, Pirogova 2, Novosibirsk 630090, Russia. E-mail address: [email protected] (K.P. Bryliakov).

omeprazole is by now manufactured via the von Unge process, which requires high catalyst loadings (30 mol % of Ti, 60 mol % of optically pure diethyltartrate), aromatic solvent (toluene), Hünig’s base (30 mol %) as additive, nonconstant temperature profile, high-molecular-weight oxidant (cumene hydroperoxide) producing high-MW byproduct, and the need in precise moisture control (by adding calculated amounts of water) [29–31]. Recently, we have reported a family of chiral titanium(IV) salalen (dihydrosalen) complexes, capable of mediating the asymmetric synthesis of anti-ulcer drugs of the PPI (Proton Pump Inhibitors) family, (S)-omeprazole and (R)-lansoprazole, by the highly enantioselective (up to 96% ee) oxidation of the corresponding pyridylmethylthiobenzimidazole precursors with H2 O2 [32]. Isoinversion behavior has been documented for the oxidation of the thioether precursors, resulting in maximum enantioselectivity at 274 ± 7 K. The reason of this isoinversion behavior was identified as the existence of two alternative reaction pathways, one prevailing at low temperature and the other at high temperatures [32]. From the technical standpoint, preparation and purification of chiral salalen ligands is a tedious procedure, which typically results in low yields and requires a thorough separation. In contrast to salalen ligands, salan ones can be readily prepared from the corresponding chiral salens in good yields [33–36]. Previously, we showed that Ti-salan complexes can serve as highly enantiose-

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2

H

N

N

OH

X

H

H

HO

X

N OH

X

N

H

HO

Y

X

OH

X

3 X= H

7 X= H, Y= Me 8 X= H, Y= OMe

4 X= Me

9 X= H, Y= Ph

5 X= OMe

10 X= OMe, Y= OMe

HN

OH

HO

R1

HO

X

13 X= H 14 X= OMe

H

H N

1. Ti(OiPr)4 R2

N

11 X= Ac 12 X= Br

6 X= H, Y= Cl

NH

N

Y

1 X= Ac 2 X= Br

R2

H

CH2Cl2 2. H2O

R1

N Ti

R2

O

O

R1

O

R2 R1

2

Ti-1...Ti-10 (salan) Ti-11...Ti-14 (salalen)

N

N S O

S

N

N H OMS

N

N H O

O LPS

CF3

Scheme 1. Chiral salan and salalen ligands, Ti(IV) complexes and sulfide precursors considered in this work.

lective catalysts for the oxidation of alkyl aryl sulfides [34–36]. It is thus tempting to test the catalytic reactivity of Ti-salan catalysts toward the asymmetric oxidation of the industrially attractive pyridylmethylthiobenzimidazoles. In this contribution, we present the asymmetric oxidation of sulfide precursors of (S)-omeprazole and (R)-lansoprazole with H2 O2 on a series of Ti-salan complexes. The catalysts demonstrate high chemo- and enantioselectivity, and nonmonotonic dependence of the enantioselectivity upon the reaction temperature. The mechanistic peculiarities of Ti-salan catalyzed sulfoxidations are discussed. 2. Experimental 2.1. General methods H2 O2 was used as commercial analytical grade 30% aqueous solution. Silica gel 60 (0.063–0.200 mm) for column chromatography was purchased from Panreac. All other chemicals were Aldrich, AlfaAesar, or Acros commercial reagents. Ti-salan complexes Ti1. . .Ti-10 [33] and Ti-salalen complexes Ti-11. . .Ti-14 [32] were prepared as previously described. Enantiomeric excess values and absolute configurations of sulfoxides, as well as the proportion of sulfide/sulfoxide/sulfone were

measured on Shimadzu LC-20HPLC chromatograph equipped with Daicel Chiralpack AD-H chiral column (250 × 4.6 mm) as described in Ref. [32]. Chiral HPLC measurements were performed at least in duplicate (until concordant results were obtained), except for kinetic measurements. The resulting ee measurement uncertainty did not exceed ±0.5% for ees falling in the range 80–94% and did not exceed ±1.0% for ees < 80%. For HPLC separation details see Supporting information for Refs. [32,34,35]. 2.2. Standard procedure for small-scale catalytic sulfoxidation Sulfide (OMS or LPS, 100 ␮mol) and the Ti-salalen catalyst (1.1 ␮mol) were dissolved in the solvent (typically: EtOAc, 6.0 mL), the mixture was thermostatted at desired temperature (typically 0 ◦ C, or −20 to +20 ◦ C for variable-temperature measurements), and 30% aqueous hydrogen peroxide (0.105 mmol of H2 O2 ) was then introduced in one portion. Stirring (500 rpm) was continued at that temperature (typically 24 h). For low-temperature experiments, the reaction times were about 30 h at −10 ◦ C and up to 10 days at −20 ◦ C. To analyze the reaction outcome, 20 ␮L aliquots of the reaction mixture were taken to a vial and immediately carefully evaporated to dryness with a stream of compressed air during ca. 15–20 s. The remaining solid was dissolved in 0.20 mL of 1% Et3 N solution in

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Table 1 Enantioselective oxidation of OMS and LPS with H2 O2 in the presence of Ti-salan and Ti-salalen catalystsa . No 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 a b c d e f g h i j

Catalyst c

(R,R)-Ti-1 (R,R)-Ti-2 (S,S)-Ti-3 (R,R)-Ti-4 (R,R)-Ti-5 (S,S)-Ti-6 (S,S)-Ti-7 (R,R)-Ti-8d (R,R)-Ti-9 (R,R)-Ti-10 (R,R)-Ti-11e (R,R)-Ti-12e (R,R)-Ti-13e (R,R)-Ti-14e (S,S)-Ti-3 (R,R)-Ti-13e (R,R)-Ti-5 (R,R)-Ti-14e (S,S)-Ti-3 (R,R)-Ti-13e (S,S)-Ti-3f (S,S)-Ti-3g (R,R)-Ti-5h (R,R)-Ti-5i (S,S)-Ti-3j (S,S)-Ti-3j

Substrate

Solvent

T [◦ C]

Conversion

Sulfoxide yield [%]b

ee [%] (config.)b

OMS OMS OMS OMS OMS OMS OMS OMS OMS OMS OMS OMS OMS OMS LPS LPS LPS LPS OMS OMS LPS LPS OMS OMS OMS LPS

EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc CH2 Cl2 CH2 Cl2 EtOAc EtOAc EtOAc EtOAc EtOAc EtOAc

0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0 +21 −20 +10 −10 0 0

90.0 84.0 91.5 94.5 97.0 64.5 75.0 98.5 84.0 95.0 14.0 44.0 97.0 98.0 97.5 99.0 94.0 98.5 98.0 100.0 89.0 81.5 97.0 88.0 99.9 99.7

77.5 81.5 88.5 91.5 93.5 59.0 70.5 90.0 76.5 89.0 13.5 42.5 94.5 94.0 95.0 96.0 91.0 93.0 92.5 96.0 87.0 78.5 91.0 83.5 94.0 96.0

48.0 (R) 66.5 (R) 90.5 (S) 90.5 (R) 91.5 (R) 26.5 (S) 59.0 (S) 71.5 (R) 52.5 (R) 87.0 (R) 50.0 (R) 75.5 (R) 94.5 (R) 94.5 (R) 91.5 (S) 93.5 (R) 88.0 (R) 92.5 (R) 82.5 (S) 96.0 (R) 89.5 (S) 83.0 (S) 88.0 (R) 84.0 (R) 93.5 (S) 94.0 (S)

[H2 O2 ]/[substrate]/[catalyst] = 105 ␮mol:100 ␮mol:1.1 mol, the oxidant was added in one portion and the mixture was stirred for 24 h. Sulfoxide yield and ee determined by chiral HPLC analysis. Reaction time 30 h. [H2 O2 ]/[substrate]/[catalyst] = 110 ␮mol:100 ␮mol:2 mol. From Ref. [32]. Reaction time 6 h. Reaction time 10 days. Reaction time 14 h. Reaction time 30 h. 2.2 mol % of the catalyst.

isopropyl alcohol, and the contents of residual sulfide, (R)- and (S)-sulfoxide, and sulfone, were analyzed by chiral HPLC as noted above. 2.3. Kinetic measurements Kinetic measurements were conducted at 0 ◦ C in EtOAc as under standard conditions (see above), but 20 ␮L aliquots were taken every 30 min. The aliquots were immediately evaporated with compressed air, dissolved in 0.2 mL of 1% Et3N solution in isopropyl alcohol and analyzed by chiral HPLC to provide relative amounts of the sulfide, sulfoxides ((R)- and (S)-), and sulfone, and the sulfoxide ee for each point. 3. Results and discussion 3.1. Enantioselective oxidation of OMS and LPS with H2 O2 on various titanium(IV) salan complexes Recently, we studied the enantioselective epoxidation of olefins with H2 O2 on chiral titanium(IV) salan complexes and found that the epoxidation enantioselectivity only depended on the steric demand of the 3,3 -aryl moieties, while electron-donating and withdrawing groups (at the 5,5 -positions) only affected the epoxidation rate [33]. We have tested a series of those Ti-salan complexes (Ti-1. . .Ti-10, Scheme 1) as catalysts for the oxidation of OMS and LPS (sulfide precursors of omeprazole and lansoprazole, respectively). The reactions were conducted in ethyl acetate which previously showed good results in Ti-salalen catalyzed sulfoxidations [32]. The obtained data are collected in Table 1. By analyzing them, one can make some preliminary conclusions: (1) the intro-

duction of electron-acceptors attenuates the catalytic activity and deteriorates the chemo- and enantioselectivity of Ti-salan complexes (entries 1–5); (2) unlike the case of olefin epoxidation [33], the presence of o-substituents at the 3-Ph rings leads to less chemo- and enantioselective catalysts (entries 6–10). Eventually, catalysts Ti-3, Ti-4, Ti-5, exhibited very similar performances, with the enantioselectivities approaching 91.5% ee (entries 3, 4, 5). Under similar conditions, Ti-salan catalysts showed somewhat lower enantioselectivities as compared to their Ti-salalen prototypes (cf. entries 1–3, 5 and 11–14 for OMS oxidations amd entries 15, 16, and 17, for LPS oxidations). For Ti-salalen catalysts, the replacement of EtOAc with CH2 Cl2 increased the sulfoxide yield and ee (cf. enties 13 and 20) [32]. For Ti-salan catalysts, a similar solvent changeover had opposite effect (cf. entries 3 and 19). We have examined the effect of concentration on the oxidation of OMS on catalyst Ti-3. Reduction of the reaction volume (2–4 times as compared to the “normal” conditions as applied in Table 1) resulted in a significant deterioration of the ee (Fig. 2A). At the same time, a two-fold dilution did not result in a comparable gain in the enantioselectivity. Interestingly, increasing the catalyst loading (when keeping the same initial concentration of OMS) sharply improved the optical purity of the resulting (S)-omeprazole (Fig. 2B, Table 1, entries 3 and 25, and Table S1, SI), approaching 94% ee at a catalyst loading of >2.5 mol %. The observed dependence is very intriguing; although the reason of the sharp enhancement of the ee when increasing the catalyst loading from 1.0 to 1.5–2.5 mol % remains unclear, the catalyst system seems to hold a good practical potential for enantioselectivity improvement. A similar rise of enantioselectivity with rising catalyst loading has been documented for the oxidation of LPS (Table 1, cf. entries 15 and 26).

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A

A

22 20 18

er

16

“normal” conditions

14 12 10 8 6 0,00

0,01

0,02

0,03

0,04

0,05

0,06

0,07

[OMS]0, M

B B

94

ee, %

93

92

91

“normal” conditions

90 0,5

1,0

1,5

2,0

2,5

3,0

Ti-3 loading, mol. % Fig. 1. Concentration dependence of the enantiomeric ratio (er) in the oxidation of OMS to (S)-omeprazole on Ti-3 (A). Dependence of the enantiomeric excess (ee) of the same reaction on the catalyst loading (B). “Normal” conditions are those in footnotes for Table 1.

Fig. 2. Kinetic plots for the oxidation of OMS with H2 O2 in the presence of Ti-3 (EtOAc, 0 ◦ C, [S]0 = [H2 O2 ]0 = 1.67·10−2 M, [S]0 :[cat] = 50)—(A): concentrations of OMS—(black) and omeprazole (sum of (R)- and (S)-enantiomers)—blue; (S)omeprazole optical purity (ee)—red. [S]0 /[S] vs. time plot for the OMS concentration after 110 min (B), and its non-linear fit (dash line). 50% conversion of OMS was achieved within 130 min. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article).

3.2. Monitoring the kinetics of sulfoxidation of OMS and LPS

1,0

Monitoring the kinetics of the oxidation of OMS on the Ti-salan catalysts revealed some features as distinct from the behavior of the Ti-salalen based systems [32]. First of all, the Ti-salan catalyst systems displayed shorter induction periods (not longer than 1 h, Fig. 2 and Figs. S1-S7, SI) [37]. Secondly, there was no steady-state regime for any of the catalysts considered, the reaction deceleration being apparent almost from the beginning. In contrast to the Ti-salalen systems (for which the enantioselectivity monotonously increased), the oxidation enantioselectivities quickly approached a maximum at <50% conversions and further gradually declined by a few per cent (Fig. 2A and S1-S5, SI) [38]. Interestingly, kinetic analysis revealed that the reactions catalyzed by Ti-1. . .Ti-4 exhibited apparent ∼2nd order in the sulfide concentration (Fig. 2B and Figs. S2-S4 of the SI) [39]. When interpreting the above results, one has to take into account that stoichiometric amounts of OMS and H2 O2 were loaded at the beginning of the reaction, whose concentrations are equal and decrease in parallel during the oxidation. Within a two-step kinetic model, with rate-limiting formation of the active titanium(IV) peroxo species [40–42] (see SI), one could assume that the rate-limiting step may be assisted by another molecule of H2 O2 , thus explaining the observed ∼2nd reaction order on the substrate. On the other hand, the oxidation of OMS on catalyst Ti-5 exhibited an apparent ca. 1st order (Fig. S1, SI), which may indicate that for Ti-5, the mechanism is more complex, such that the interaction

0,8

[S]/[S]0

0,6 0,4 1

0,2 0,0

4 0

100

200

300

2

3 400

500

600 t, min

Fig. 3. Kinetics of oxidation of OMS with H2 O2 on Ti-3 (EtOAc, 0 ◦ C, [S]0 = 1.67·10−2 M, [S]0 :[cat] = 50): [H2 O2 ]0 :[S]0 = 1:1—(1), [H2 O2 ]0 :[S]0 = 1.33:1—(2), [H2 O2 ]0 :[S]0 = 2:1—(3), [H2 O2 ]0 :[S]0 = 3:1—(4).

with H2 O2 is relatively fast and may not be correctly taken as the rate-limiting step. Increasing the amount of H2 O2 accelerated the reaction (Fig. 3) and altered the observed reaction order. In particular, when excess of H2 O2 was used, the observed reaction order decreased to <1 (33% excess of H2 O2 : n = 0.88; 100% excess of H2 O2 : n = 0.60). Moreover, under the conditions of high excess of H2 O2 , there was no

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3,2

A

3,1 3,0

Ln(er)

2,9

273 K

2,8 2,7 2,6 2,5 2,4 2,3 3.3

3.4

3.5

3.6

3.7

3.8

3.9

4.0

1000/T

B

Fig. 4. Kinetic plots for the oxidation of OMS with H2 O2 on Ti-3 (EtOAc, 0 ◦ C, [S]0 = 1.67·10−2 M, [S]0 :[cat] = 50, [H2 O2 ]0 :[S]0 = 2)—(A): concentrations of OMS—(black) and omeprazole (sum of (R)- and (S)-enantiomers) − blue; (S)omeprazole optical purity—red. [S]0 /[S] vs. time plot for the OMS concentration after 50 min (B) and its nonlinear fit (dash line). 50% conversion of OMS was achieved within 90 min. (For interpretation of the references to colour in this figure legend, the reader is referred to the web version of this article).

Fig. 5. Modified Eyring plot for the oxidation of OMS on catalyst Ti-5. er − enantiomeric ratio (100 + ee)/(100-ee).

Scheme 2. Proposed reaction schemes for sulfoxidation in the presence of water. L is solvent or vacancy.

enantioselectivity decrease, the latter remaining in the range 93.0. . .93.5% ee (Fig. 4 and S6). At high conversions (>90%), the reactions visibly decelerated owing to nearly complete sulfide consumption (Fig. 3). Noticeably, while the oxidation of OMS was relatively fast with catalysts Ti-3, Ti-4, Ti-5 (ensuring 50% conversion within 70 min (Ti-4) or 130 min (Ti-3)), catalysts Ti-1 and Ti-2 with electronwithdrawing substituents showed much lower reaction rates (with 50% conversions achieved at 230 min (Ti-1) or 300 min (Ti-2), see Figs. S1-S5 of the SI). Apparently, the presence of electron-acceptors at the ligand core must lead to a more electrophilic (and hence more reactive) oxidizing species, which requires a higher activation barrier for the rate-limiting formation of the active oxidant (cf. Ref. [32]), which stage is followed by relatively fast oxygen transfer to the sulfide. Earlier, we came to the same conclusions when discussing the oxidation of benzyl phenyl sulfide in the presence of ent-Ti-1 [36].

+20 ◦ C (Fig. 5 and S8, SI) demonstrated a maximum at ca. 273 K, indicating isoinversion behavior similar to that exhibited by Tisalalen sulfoxidation catalysts [32]. The origin of the isoinversion behavior was previously discussed in terms of the changeover of the oxidation mechanism [32]. In particular, it was proposed that at high temperature, a water-coordinated titanium-salalen peroxo complex is the major oxygen-transferring intermediate. At low temperatures (<273 K), water freezes out, thus leading to a water-free intermediate, responsible for the less-enantioselective oxidation pathway (Scheme 2). DFT calculations witness that water-coordinated intermediate is ca. 7 kcal/mol lower in energy than EtOAc-coordinate one [43], thus suggesting that the latter can only predominate under water-deficient conditions, i.e., below the melting point of H2 O. We believe that a similar situation is the case for Ti-salan based catalysts.

3.3. Temperature dependence of sulfoxidation enantioselectivity

4. Conclusions

For Ti-salalen catalysts Ti-13 an Ti-14, the optimum temperature range was 273. . .283 K, while performing the reaction at higher or lower temperature resulted in significant depletion of the enantiomeric excess [32]. Similarly, the Ti-salan catalysts demonstrated reduced enantioselectivity at temperatures below or above 273 K (cf. entries 15, 21, 22 for Ti-3 and 5, 23, 24 for Ti-5 in Table 1). Modified Eyring plots (Ln(enantiomeric ratio) vs. T−1 ) for oxidations of OMS and LPS performed in the temperature range −20 up to

Titanium(IV) salan complexes have been shown to catalyze the asymmetric sulfoxidation of two pyridylmethylthiobenzimidazoles to anti-ulcer drugs of the PPI family (S)-omeprazole and (R)-lansoprazole with aqueous H2 O2 . High sulfoxide yields (up to >95%) and enantioselectivities (up to 94% ee) have been achieved. These values are similar to those demonstrated by the commercial von Unge’s system; additional advantages of the Ti-salan systems are the simplicity of manipulations, cheap and environmen-

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tally benign oxidant and non-aromatic solvent, and low catalyst loading (1–2 mol %). The introduction of electron-withdrawing substituents leads to less active and less enantioselective catalysts. Analysis of the oxidation kinetics suggests that the reaction is most likely rate-limited by formation of the active (presumably peroxotitanium(IV)) species, followed by a faster oxygen transfer to the substrate. The temperature dependence of the sulfoxidation enantioselectivity in the presence of Ti-salan complexes is nonmonotonic, demonstrating isoinversion behavior with a maximum at ca. 273 K, which temperature may be recommended for preparative catalytic reactions. Acknowledgment The present work was supported by the Russian Scientific Foundation, grant 14-13-00158. Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.cattod.2016.03. 006. References [1] P. Pitchen, H.B. Kagan, Tetrahedron Lett. 25 (1984) 1049–1052. [2] P. Pitchen, M. Desmukh, E. Dunach, H.B. Kagan, J. Am. Chem. Soc. 106 (1984) 8188–8193. [3] F. Di Furia, G. Modena, R. Seraglia, Synthesis (1984) 325–326. ˜ J.P. Hildebrand, in: E.N. Jacobsen, A. Pfaltz, H. Yamamoto [4] C. Bolm, K. Muniz, (Eds.), Comprehensive Asymmetric Catalysis, Springer, Berlin, 1999, pp. 697–712. [5] H.B. Kagan, in: I. Ojima (Ed.), Catalytic Asymmetric Synthesis, 2nd ed., Wiley, New York, 2000, pp. 327–356. [6] I. Fernandez, N. Khiar, Chem. Rev. 103 (2003) 3651–3705. [7] J. Legros, J.R. Dehli, C. Bolm, Adv. Synth. Catal. 347 (2005) 9–31. [8] D.J. Ramón, M. Yus, Chem. Rev. 106 (2006) 2126–2208. [9] K.P. Bryliakov, E.P. Talsi, Curr. Org. Chem. 12 (12) (2008) 386–404. [10] K.P. Volcho, N.F. Salakhutdinov, Russ. Chem. Rev. 78 (2009) 457–464. ´ ´ [11] E. Wojaczynska, J. Wojaczynski, Chem. Rev. 110 (2010) 4303–4356. [12] K.A. Stingl, S.B. Tsogoeva, Tetrahedron: Asymmetry 21 (2010) 1055–1074. [13] G.E. O’Mahony, P. Kelly, S.E. Lawrence, A.R. Maguire, ARKIVOC (2011) 1–110. [14] A. Lattanzi, in: A. Evans (Ed.), Science of Synthesis, Stereoselective Synthesis 3, Georg Thieme Verlag, Stuttgart, 2011, pp. 973–1015.

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Please cite this article in press as: E.P. Talsi, K.P. Bryliakov, Ti-Salan catalyzed asymmetric sulfoxidation of pyridylmethylthiobenzimidazoles to optically pure proton pump inhibitors, Catal. Today (2016), http://dx.doi.org/10.1016/j.cattod.2016.03.006