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ACS Catalysis
526. (b) Muller, C. E.; Schreiner, P. R. Angew. Chem. Int. Ed. 2011,
50, 6012–6042.
CONCLUSION
1
2
3
4
5
6
7
8
The synthesis of polystyreneꢀsupported isothiourea catalyst 6
(4) (a) Benaglia, M.; Puglisi, A.; Cozzi, F. Chem. Rev. 2003, 103,
3401–3429. (b) Trindade, A. F.; Gois, P. M. P.; Alfonso, C. A. M.
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2009, 109, 815–838.
(5) In addition, immobilized peptides and transition metal catalysts
have been used for the KR of alcohols: (a) Copeland, G. T.; Miller, S.
J. J. Am. Chem. Soc. 2001, 123, 6496–6502. (b) Gissibl, A.; Finn, M.
G.; Reiser, O. Org. Lett. 2005, 7, 2325–2328. (c) Gissibl, A.; Padié,
C.; Hager, M.; Jaroschik, F.; Rasappan, R.; CuevasꢀYañez, E.; Turrin,
C.ꢀO.; Caminade, A.ꢀM.; Majoral, J.ꢀP.; Reiser, O. Org. Lett. 2007, 9,
2895–2898. (d) Schätz, A.; Hager, M.; Reiser, O. Adv. Funct. Mater.
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(6) Clapham, B.; Cho, C.ꢀW.; Janda, K. D. J. Org. Chem. 2001, 66,
868–873.
(7) Pelotier, B.; Priem, G.; Campbell, I. B.; Macdonald, S. J. F.;
Anson, M. S. Synlett, 2003, 5, 679–683
(8) (a) Ishihara, K.; Kosugi, Y.; Akakura, M. J. Am. Chem. Soc.
2004, 126, 12212–12213. (b) Kosugi, Y.; Akakura, M.; Ishihara, K.
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was
achieved
in
four
steps
from
(R)ꢀ2ꢀ((R)ꢀ
amino(phenyl)methyl)ꢀ3ꢀmethylbutanꢀ1ꢀol in 48% overall
yield. The KR of a range of secondary alcohols was demonꢀ
strated using 6 as catalyst (1 mol%), with the substrate scope
including benzylic, allylic and propargylic alcohols, cycloalꢀ
kanol derivatives and a 1,2ꢀdiol (28 examples). The majority
of examples were resolved with good to excellent selectivity
factors (s up to > 600), showing this process has a broad subꢀ
strate scope, well beyond that of other solidꢀsupported Lewis
base catalysts reported to date. The recyclability of the catalyst
was demonstrated for the resolution of a single alcohol (15
cycles), and for the sequential resolution of 10 different alcoꢀ
hols using different anhydrides, with no significant loss in
activity or selectivity and with no crossꢀcontamination obꢀ
served. Based on the high catalyst activity and recyclability, a
continuous flow process was developed which was applied for
the efficient KR of 9 different alcohols and also utilized on a
28.8 mmol scale. Current work is focused on using this new
catalyst for other isothioureaꢀcatalyzed reactions through apꢀ
plication in batch and continuous flow processes.33
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
(10) In addition, the equivalents of anhydride and base were increꢀ
mentally increased over the recycling process, indicating some cataꢀ
lyst degradation.
ASSOCIATED CONTENT
(11) For reviews on the use of solidꢀsupported chiral catalysts in
continuous flow processes see: (a) Puglisi, A.; Benaglia, M.; Chiroli,
V. Green Chem. 2013, 15, 1790–1813. (b) RodríguezꢀEscrich, C.;
Pericàs, M. A. Eur. J. Org. Chem. 2015, 2015, 1173–1188. (c)
Atodiresei, I.; Vila, C.; Rueping, M. ACS Catal. 2015, 5, 1972–1985.
(12) The KR of a 1,2ꢀdiol using a Cu(II)ꢀazabis(oxazoline) catalyst
supported on a Co/C nanoparticle has been reported in continuous
flow, see ref. 5e. For the nonꢀcatalytic acylative parallel KR of amines
in continuous flow see: Kreituss, I.; Bode, J. W. Nature Chem. 2017,
9, 446–452.
The Supporting Information is available free of charge on the
ACS Publications website at DOI:
Experimental procedures; characterization data for novel comꢀ
pounds; 1H and 13C NMR spectra and HPLC traces.
AUTHOR INFORMATION
Corresponding Author
* mapericas@iciq.es (M.A.P.)
* ads10@stꢀandrews.ac.uk (A.D.S.)
(13) For a review see: Merad, J.; Pons, J.ꢀM.; Chuzel, O.; Bressy,
C.; Eur. J. Org. Chem. 2016, 2016, 5589–5610.
Author Contributions
(14) Birman, V. B.; Li, X. Org. Lett. 2006, 8, 1351–1354.
(15) (a) Birman, V. B.; Guo, L. Org. Lett. 2006, 8, 4859–4861. (b)
Birman, V. B.; Li, X. Org. Lett. 2008, 10, 1115–1118. (c) Zhang, Y.;
Birman, V. B. Adv. Synth. Catal. 2009, 351, 2525–2529. (d) Xu, Q.;
Zhou, H.; Geng, X.; Chen, P. Tetrahedron 2009, 65, 2232–2238. (e)
Shiina, I.; Nakata, K.; Ono, K.; Sugimoto, M.; Sekiguchi, A.. Chem.
Eur. J. 2010, 16, 167–172. (f) Shiina, I.; Ono, K.; Nakata, K. Chem.
Lett. 2011, 40, 147–149. (g) Li, X.; Jiang, H.; Uffman, E. W.; Guo,
L.; Zhang, Y.; Yang, X.; Birman, V. B. J. Org. Chem. 2012, 77,
1722–1737. (h) Nakata, K.; Gotoh, K.; Ono, K.; Futami, K.; Shiina, I.
Org. Lett. 2013, 15, 1170–1173. (i) Shiina, I.; Ono, K.; Nakahara, T.
Chem. Commun. 2013, 49, 10700–10702.
(16) (a) Belmessieri, D.; Joannesse, C.; Woods, P. A.; MacGregor,
C.; Jones, C.; Campbell, C. D.; Johnston, C. P.; Duguet, N.; Concelꢀ
lón, C.; Bragg, R. A.; Smith, A. D. Org. Biomol. Chem. 2011, 9, 559–
570. (b) Musolino, S. F.; Ojo, O. S.; Westwood, N. J.; Taylor J. E.;
Smith A. D. Chem. Eur. J. 2016, 22, 18916–18922.
(17) (a) Izquierdo, J.; Pericàs, M. A. ACS Catal. 2016, 6, 348–356.
(b) Wang, S.; Izquierdo, J.; RodríguezꢀEscrich, C.; Pericàs, M. A.
ACS Catal. 2017, 7, 2780–2785. (c) Wang, S.; RodríguezꢀEscrich, C.;
Pericàs, M. A. Angew. Chem. Int. Ed. 2017, 56, 15068–15072.
(18) (a) Joannesse, C.; Johnson, C. P.; Concellón, C.; Simal, C,
Philp, D.; Smith, A. D. Angew. Chem. Int. Ed. 2009, 48, 8914–8918.
(b) Belmessieri, D.; Morrill, L. C.; Simal, C.; Slawin, A. M. Z.;
Smith, A. D. J. Am. Chem. Soc. 2011, 133, 2714–2720. (c) Maji, B.;
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Matviiksuk, A.; Greenhalgh, M. D.; Antúnez, D.ꢀJ. B.; Slawin, A. M.
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All authors have given approval to the final version of the manuꢀ
script.
ACKNOWLEDGMENT
We thank the EPSRC Centre for Doctoral Training in Critical
Resource Catalysis (CRITICAT, grant code EP/L016419/1,
R.M.N.P.) for funding. Financial support from the EPSRC
(EP/K000411/1) is gratefully acknowledged (R.C.). The European
Research Council under the European Union’s Seventh Frameꢀ
work Programme (FP7/2007ꢀ2013) ERC Grant Agreement No.
279850 is also acknowledged. A.D.S. thanks the Royal Society
for a Wolfson Research Merit Award. We also thank the EPSRC
UK National Mass Spectrometry Facility at Swansea University.
C.R.ꢀE. and M.A.P. acknowledge the financial support from
CERCA Programme/Generalitat de Catalunya, MINECO
(CTQ2015ꢀ69136ꢀR, AEI/MINECO/FEDER, UE and Severo
Ochoa Excellence Accreditation 2014–2018, SEVꢀ2013ꢀ0319)
and DEC Generalitat de Catalunya (Grant 2014SGR827).
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