Asymmetric Amination of Secondary Alcohols by using a Redox-Neutral Two-Enzyme Cascade

Article abstract of DOI:10.1002/cctc.201500785

Multienzyme cascade approaches for the synthesis of optically pure molecules from simple achiral compounds are desired. Herein, a cofactor self-sufficient cascade protocol for the asymmetric amination of racemic secondary alcohols to the corresponding chiral amines was successfully constructed by employing an alcohol dehydrogenase and a newly developed amine dehydrogenase. The compatibility and the identical cofactor dependence of the two enzymes led to an ingenious in situ cofactor recycling system in the one-pot synthesis. The artificial redox-neutral cascade process allowed the transformation of racemic secondary alcohols into enantiopure amines with considerable conversions (up to 94 %) and >99 % enantiomeric excess at the expense of only ammonia; this method thus represents a concise and efficient route for the asymmetric synthesis of chiral amines. If you know what amine: A redox-neutral two-enzyme cascade encompassing an alcohol dehydrogenase (ADH) and an amine dehydrogenase (AmDH) is constructed for the synthesis of chiral amines from the corresponding racemic alcohols in one pot to afford considerable conversions (up to 94 %) and high enantiomeric excess values (>99 %) at the expense of only ammonia.

Full text of DOI:10.1002/cctc.201500785

DOI: 10.1002/cctc.201500785
Communications
Asymmetric Amination of Secondary Alcohols by using
a Redox-Neutral Two-Enzyme Cascade
Fei-Fei Chen,[a] You-Yan Liu,[b, c] Gao-Wei Zheng,*[a] and Jian-He Xu*[a]
Multienzyme cascade approaches for the synthesis of optically
pure molecules from simple achiral compounds are desired.
Herein, a cofactor self-sufficient cascade protocol for the asym-
metric amination of racemic secondary alcohols to the corre-
sponding chiral amines was successfully constructed by em-
ploying an alcohol dehydrogenase and a newly developed
amine dehydrogenase. The compatibility and the identical co-
factor dependence of the two enzymes led to an ingenious
in situ cofactor recycling system in the one-pot synthesis. The
artificial redox-neutral cascade process allowed the transforma-
tion of racemic secondary alcohols into enantiopure amines
with considerable conversions (up to 94%) and >99% enan-
tiomeric excess at the expense of only ammonia; this method
thus represents a concise and efficient route for the asymmet-
ric synthesis of chiral amines.
cesses encompassing enzymes such as w-transaminase, mono-
amine oxidase, and lyase have been constructed.[4] As green
and renewable biobased feedstocks, alcohols are increasingly
identified as suitable initial substrates for amine synthesis by
metal-catalyzed amination, with some shortcomings including
poor stereoselectivity, less atom efficiency, and the use of toxic
and expensive metals.[5] Initially, biocatalytic transformations of
a-hydroxy acids into a-amines were studied by employing
amino acid dehydrogenases and alcohol dehydrogenases.[6] Re-
cently, Kroutil and co-workers first reported a series of redox-
neutral multienzymatic networks involving alcohol dehydro-
genase (ADH), w-transaminase, and alanine dehydrogenase for
the amination of primary alcohols and secondary alcohols.[7]
Notably, in artificial multienzymatic networks, the transforma-
tion of alcohol substrates into the desired amines mainly con-
sists of two tandem steps: one, alcohol dehydrogenation cata-
lyzed by an ADH (for primary alcohols) or two stereoselectively
complemental ADHs (for racemic secondary alcohols) to give
the corresponding ketone; two, subsequent reductive amina-
tion catalyzed by an w-transaminase by using l-alanine as the
amino donor. More recently, Skerra and co-workers succeeded
in extending the above concept to the synthesis of a structural-
ly more complex diamine from the biobased diol isosorbide.[8]
The aim of this study was to construct a new redox-neutral
two-enzyme cascade process for the preparation of chiral
amines from racemic secondary alcohols (Scheme 1). In the
Enantiomerically pure chiral amines are increasingly used as
important precursors for the synthesis of biologically active
molecules, and the development of efficient and cost-effective
methods for their asymmetric synthesis is in high demand.[1]
Compared to classic chemical methods for the manufacture of
chiral amines, including asymmetric hydrogenation of enam-
ines/imines, a variety of artificially developed enzymes could
serve as a potential “green alternative” generally featuring
novel activity, mild reaction conditions, high regioselectivity,
high stereoselectivity, and impressive conversions.[2] A remark-
able case is the asymmetric synthesis of sitagliptin from prosi-
tagliptin ketone by using an w-transaminase developed by
protein engineering.[3]
The preparation of chiral amines from simple and inexpen-
sive starting materials through biocatalytic routes is attracting
growing interest. A variety of exquisite enzymatic cascade pro-
Scheme 1. A redox-neutral two-enzyme cascade for the amination of race-
mic secondary alcohols to chiral amines. ADH: Alcohol dehydrogenase;
AmDH: Amine dehydrogenase.
[a] F.-F. Chen, G.-W. Zheng, Prof. J.-H. Xu
State Key Laboratory of Bioreactor Engineering
Shanghai Collaborative Innovation Center for Biomanufacturing
East China University of Science and Technology
130 Meilong Road, Shanghai 200237 (P.R. China)
E-mail: gaoweizheng@ecust.edu.cn
cascade process, the racemic secondary alcohols were non-
stereoselectively oxidized by an alcohol dehydrogenase to the
corresponding ketones and then aminated by an amine dehy-
drogenase (AmDH) to the chiral amines by using ammonia as
the amino donor. Simultaneously, the cofactor NADH formed
in the first step served as the reducing agent in the reductive
amination step, whereas the resulting NAD+ was reused for
the upstream oxidation step. The newly designed two-enzyme
cascade pathway consumes only ammonia and avoids the ad-
dition of alanine and an external reducing agent; it therefore
jianhexu@ecust.edu.cn
[b] Prof. Y.-Y. Liu
School of Chemistry and Chemical Engineering
Guangxi University
Nanning 530004, Guangxi (P.R. China)
[c] Prof. Y.-Y. Liu
Guangxi Key Laboratory of Biorefinery
Guangxi Academy of Sciences
Nanning 530003, Guangxi (P.R. China)
Supporting Information for this article is available on the WWW under
http://dx.doi.org/10.1002/cctc.201500785.
ChemCatChem 2015, 7, 3838 – 3841
3838
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communications
represents a more concise redox-neutral process for the syn-
thesis of chiral amines from racemic secondary alcohols.
Amine dehydrogenases are capable of catalyzing the asym-
metric reductive amination of prochiral ketones to the corre-
sponding chiral amines, with the consumption of inorganic
ammonia. AmDHs were first developed by Bommarius and co-
workers through several rounds of protein engineering by
using amino acid dehydrogenases as the evolution tem-
plates.[9] More recently, Li also obtained an AmDH from Rhodo-
coccus sp. M4 phenylalanine dehydrogenase by directed evolu-
tion.[10] In our laboratory, an NADH-dependent leucine dehy-
drogenase from Exiguobactertium sibiricum (EsLeuDH) was re-
cently identified and applied to the stereoselective synthesis of
l-tert-leucine,[11] a valuable chiral building block in the pharma-
ceutical industry.[12] However, EsLeuDH has merely undetect-
able levels of activity towards ketone substrates in comparison
with a-keto acid substrates. With the aim of further expanding
its synthetic scope to give more structurally diverse products,
the two-site mutation (K77S/N270L) identified by Bommarius[9]
was introduced to EsLeuDH. As a consequence, the double
mutant EsLeuDH-DM (K77S/N270L) obtained by the two-site
mutagenesis exhibited considerable activities towards a variety
of ketones (Table 1).
To match the cofactor of EsLeuDH-DM, an NAD+-dependent
ADH for the oxidation of secondary alcohols should be select-
ed.[13] Furthermore, an ADH with low enantioselectivity was
preferable,[14] as only 50% of the rac-alcohol could be oxidized
by an ADH with perfect stereoselectivity.[15] Initially, we tested
approximately 20 NADH-dependent ADHs preserved in our
laboratory (Table S1, Supporting Information), and an ADH
(ScCR) from Streptomyces coelicolor[16] was identified with ap-
preciable activity towards the desired secondary alcohols and
capacity to convert both isomers of the racemic secondary al-
cohols into the corresponding ketones.
Further optimization of the conditions for the cascade reac-
tions was performed by employing rac-2-pentanol as the
model substrate. As shown in Table 2, at pH 9.5, an unusual
Table 2. Optimization of the two-enzyme cascade reaction.[a]
Entry pH
NAD+ [mm] Alcohol [%][b] Ketone [%][b] Amine [%][b]
1
2
3
4
5
6
10.5 2.0
48.5
1.6
0.8
2.2
6.9
4.4
6.1
9.0
4.7
3.8
4.0
47.1
92.3
90.2
93.1
89.3
77.1
9.5 2.0
8.5 2.0
9.5 1.0
9.5 0.5
9.5 0.2
18.9
[a] Reaction conditions: Mixture (1 mL) of rac-2-pentanol (50 mm), ADH
ScCR (lyophilized cell-free extract, 10 mg), AmDH EsLeuDH-DM (lyophi-
lized cell-free extract, 10 mg), NAD+ (various concentrations), and NH4Cl/
NH4OH buffer (2m, various pH values) at 308C, 1000 rpm. [b] Composi-
tions were analyzed by GC analysis by comparing peak areas.
Table 1. Activity of EsLeuDH-DM towards various ketones.[a]
Substrate
Specific activity
Substrate
Specific activity
À1
À1
[mUmgprotein
]
[mUmgprotein
]
condition for common ADHs,[7,17] the cascade reaction afforded
92.3% amine (Table 2, entry 2), whereas the conversion of alco-
hol decreased sharply under harsher pH conditions (pH 10.5).
A decrease in the NAD+ loading from 2.0 to 1.0 mm resulted
in a slight increase in the amount of amine formed (Table 2,
entry 4), which is in agreement with the fact that a higher con-
centration of NAD+ could impair the amination activity of
EsLeuDH-DM (Figure S1). Reducing the NAD+ loading further,
however, hindered the cascade process.
1.4Æ0.2
6.5Æ0.2
137Æ7
796Æ29
82.8Æ0.4
2559Æ58
868Æ40
403Æ13
2465Æ5
287Æ32
Under the optimized conditions (Table 2, entry 4), time-
course analysis revealed that the formation of 2-pentanamine
reached a maximum (93%) at approximately 24 h (Figure 1),
after which the remaining 2-pentanol was maintained at a rela-
tively low level. Notably, a certain amount of 2-pentanone
(ꢀ4%) was detected throughout the course of the cascade re-
action. The high conversion of alcohol into amine indicates
that the equilibrium is in favor of amine synthesis, whereas the
synthesis of amine by using the w-transaminase is commonly
retarded by an adverse equilibrium position and byproduct in-
hibition.[18]
760Æ44
98.5Æ0.8
4.5Æ0.6
3628Æ101
To investigate the synthetic scope of the two-enzyme cas-
cade, we tried to apply the above methodology to the conver-
sion of various alcohols into the corresponding amines
(Table 3). As both the ADH (ScCR) and AmDH (EsLeuDH-DM)
had broad substrate specificity, the secondary alcohols tested
were converted into the desired corresponding amines. Conse-
quently, over 90% conversion of the alcohols into the corre-
490Æ18
11.8Æ1.2
1.4Æ0.5
[a] Reactions were performed in NH4Cl/NH4OH buffer (2m, pH 9.5) con-
taining 0.1 mm NADH and 20 mm ketone substrate at 308C.
ChemCatChem 2015, 7, 3838 – 3841
www.chemcatchem.org
3839
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communications
alcohol substrates such as rac-2-pentanol, the cascade afforded
>99% enantiomeric excess (ee), and thus, this route formally
represents a biocatalytic method to access optically pure chiral
products from simple racemates.
The absolute configurations of the products with only one
chiral center bearing an amino group were all identified to
possess the (R) configuration (for details of the assignment of
absolute configuration, see the Supporting Information), which
is in agreement with previous reports that the developed
amine dehydrogenases of this family preserve the enantiose-
lectivity of the wildtypes.[9,10]
In summary, by coupling an amine dehydrogenase
(EsLeuDH-DM) with a nonstereoselective alcohol dehydrogen-
ase, a redox self-sufficient and concise two-enzyme cascade
process was constructed that was capable of aminating race-
mic secondary alcohols into the desired optically pure chiral
amines, with considerable conversions (up to 94%) and >99%
enantiomeric excess. To the best of our knowledge, this is the
first report of the enzymatic synthesis of chiral amines from al-
cohols by employing a redox-neutral two-enzyme cascade con-
sisting of an alcohol dehydrogenase and an amine dehydro-
genase. Further attempts at protein engineering and process
development may be necessary to improve the performance
of the one-pot transformation and to minimize the waste of
salts. We envision that this elegant enzymatic route might rep-
resent an easy and efficient biocatalytic route for the produc-
tion of highly valued chiral amines.
Figure 1. Time course of the two-enzyme cascade reaction by employing
rac-2-pentanol as the substrate. Comp.: Composition.
Table 3. Biocatalytic synthesis of amines from alcohols through the
redox-neutral two-enzyme cascade.[a]
Entry Substrate Structural formula Alcohol Ketone Amine ee
[%][b]
[%][b]
[%][b] [%][c]
1
2
rac-1a
rac-2a
2
4
4
94
73
>99 (R)
23
>99 (R)
3
4
5
rac-3a
rac-4a
rac-5a
40
3
3
4
5
57
93
29
n.d.[d]
>99 (R)
>99 (R)
Experimental Section
General information
66
Both the wildtype EsLeuDH and the ADH (ScCR) were cloned into
E. coli BL21 (DE3) cells by using plasmid pET-28a (+) as previously
described[11,16] and were stocked at À808C.
6
7
8
6a
1
23
55
2
2
2
97
75
43
n.a.[e]
n.d.[d]
n.d.[d]
GC analysis for determining the conversion was performed with
a Shimadzu-2014 gas chromatograph equipped with a flame ioni-
zation detector (FID) and an Agilent J&W DB-1701 capillary column
(30 m”0.25 mm, 0.25 mm) by using nitrogen as the carrier gas; for
determination of the enantiomeric excess values, an Agilent J&W
CP-Chiralsil-DEX CB capillary column (25 m”0.25 mm, 0.25 mm)
was equipped. To measure the conversion, the relative amount (re-
ported in %) of each component (alcohol, ketone, and amine) was
determined according to the proportion of each peak area in the
total peak area of the three compositions. The enantiomeric excess
values of the amine products were determined through GC analy-
sis on a chiral stationary phase after derivatization by comparison
with commercially available reference materials. For derivatization,
samples in CH2Cl2 (1 mL) were supplemented with acetic anhydride
(100 mL) and pyridine, then shaken for 4 h (168C, 180 rpm), after
which water (500 mL) was added to hydrolyze the excess amount
of acetic anhydride. The organic phase was extracted and finally
dried with anhydrous MgSO4 before GC analysis on a chiral station-
ary phase.
rac-7a
rac-8a
9
9a
60
72
5
7
35
21
n.a.[e]
10
rac-10a
>99 (R)
[a] Reaction conditions: Mixture (1 mL) of substrate (50 mm), ADH ScCR
(lyophilized cell-free extract, 10 mg), AmDH EsLeuDH-DM (lyophilized cell-
free extract, 10 mg), NAD+ (1 mm), NH4Cl/NH4OH buffer (2m, pH 9.5) at
308C, 1000 rpm. [b] Compositions were analyzed by GC analysis by com-
paring peak areas. [c] The ee values of the amines were determined by
GC analysis on a chiral stationary phase after derivation. [d] n.d.=not de-
termined. [e] n.a.=not applicable.
One-pot procedure
sponding amines was achieved for three alcohol substrates
An analytical-scale one-pot reaction mixture (1 mL) containing
NH4Cl/NH4OH buffer (2m, pH 9.5), alcohol substrate (50 mm), NAD+
(i.e., rac-1a, rac-4a, and 6a), and for some racemic secondary
ChemCatChem 2015, 7, 3838 – 3841
www.chemcatchem.org
3840
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Communications
[5] a) R. Grigg, T. R. B. Mitchell, S. Sutthivaiyakit, N. Tongpenyai, J. Chem.
Soc. Chem. Commun. 1981, 611 –612; b) Y. Watanabe, Y. Tsuji, Y. Ohsugi,
Tetrahedron Lett. 1981, 22, 2667–2670; c) D. Pingen, O. Diebolt, D. Vogt,
ChemCatChem 2013, 5, 2905–2912; d) M. Lafrance, M. Roggen, E. M.
Carreira, Angew. Chem. Int. Ed. 2012, 51, 3470–3473; Angew. Chem.
2012, 124, 3527–3530; e) A. J. A. Watson, A. C. Maxwell, J. M. J. Williams,
J. Org. Chem. 2011, 76, 2328–2331; f) D. Pingen, C. Müller, D. Vogt,
Angew. Chem. Int. Ed. 2010, 49, 8130–8133; Angew. Chem. 2010, 122,
8307–8310.
(1 mm), and lyophilized cell-free extracts of EsLeuDH-DM (10 mg)
and ScCR (10 mg). For optimization of the two-enzyme cascade
process, the pH of the NH4Cl/NH4OH buffer (2m) was varied from
8.5 to 10.5, and the concentration of NAD+ was varied from 0.2 to
2.0 mm. The mixture was shaken at 308C, 1000 rpm for 24 h, after
which it was quenched by adding NaOH (10m, 200 mL) and extract-
ed with CH2Cl2 (1 mL, for once). The organic extract was dried with
anhydrous MgSO4 and analyzed by GC.
[6] a) C. Wandrey, E. Fiolitakis, U. Wichmann, M. R. Kula, Ann. N. Y. Acad. Sci.
1984, 434, 091–094; b) W. Hummel, M. R. Kula in EJB Reviews 1989,
Vol. 1989 (Eds.: P. Christen, E. Hofmann), Springer-Verlag, Berlin, 1989,
pp. 85–97; c) V. Resch, W. M. F. Fabian, W. Kroutil, Adv. Synth. Catal.
2010, 352, 993–997.
[7] a) J. H. Sattler, M. Fuchs, K. Tauber, F. G. Mutti, K. Faber, J. Pfeffer, T. Haas,
W. Kroutil, Angew. Chem. Int. Ed. 2012, 51, 9156–9159; Angew. Chem.
2012, 124, 9290–9293; b) K. Tauber, M. Fuchs, J. H. Sattler, J. Pitzer, D.
Pressnitz, D. Koszelewski, K. Faber, J. Pfeffer, T. Haas, W. Kroutil, Chem.
Eur. J. 2013, 19, 4030–4035.
A
preparative-scale mixture (10 mL) containing NH4Cl/NH4OH
buffer (2m, pH 9.5), rac-1a substrate (44.1 mg, 0.5 mmol), NAD+
(10 mmol), lyophilized EsLeuDH-DM cell-free extract (100 mg), and
lyophilized ScCR cell-free extract (100 mg). The mixture was shaken
at 308C, 250 rpm for 24 h, after which NaOH solution (10m, 2 mL)
was added to stop the reaction. The resulting mixture was extract-
ed with CH2Cl2 (3”10 mL), and the extract was combined, dried
with anhydrous MgSO4, and concentrated under reduced pressure.
Then, the remaining was supplemented with HCl ethereal solution
(2m, 2 mL) to precipitate the amine hydrochloride. The final precip-
itate was evaporated again under reduced pressure and dried
under vacuum to give 1c·HCl. Yield: 13.2 mg (21%). 1H NMR
(400 Hz, CDCl3): d=0.96 (t, 3H, J=7.3 Hz), 1.41 (d, 3H, J=6.6 Hz),
1.46 (q, 2H, J=7.5 Hz), 1.56–1.65 (m, 1H), 1.75–1.84 (m, 1H), 3.26–
3.42 (m, 1H), 8.06–8.60 ppm (br.m, 3H).[19]
[8] A. Lerchner, S. Achatz, C. Rausch, T. Haas, A. Skerra, ChemCatChem
2013, 5, 3374–3383.
[9] a) M. J. Abrahamson, E. Vµzquez-Figueroa, N. B. Woodall, J. C. Moore,
A. S. Bommarius, Angew. Chem. Int. Ed. 2012, 51, 3969–3972; Angew.
Chem. 2012, 124, 4036–4040; b) M. J. Abrahamson, J. W. Wong, A. S.
Bommarius, Adv. Synth. Catal. 2013, 355, 1780–1786; c) S. K. Au, B. R.
Bommarius, A. S. Bommarius, ACS Catal. 2014, 4, 4021–4026; d) B. R.
Bommarius, M. Schurmann, A. S. Bommarius, Chem. Commun. 2014, 50,
14953–14955.
[10] L. J. Ye, H. H. Toh, Y. Yang, J. P. Adams, R. Snajdrova, Z. Li, ACS Catal.
2015, 5, 1119–1122.
Acknowledgements
[11] J. Li, J. Pan, J. Zhang, J. H. Xu, J. Mol. Catal. B 2014, 105, 11–17.
[12] A. S. Bommarius, M. Schwarm, K. Stingl, M. Kottenhahn, K. Huthmacher,
K. Drauz, Tetrahedron: Asymmetry 1995, 6, 2851–2888.
[13] a) D. Romano, R. Villa, F. Molinari, ChemCatChem 2012, 4, 739–749;
b) W. Kroutil, H. Mang, K. Edegger, K. Faber, Adv. Synth. Catal. 2004, 346,
125–142; c) W. Kroutil, H. Mang, K. Edegger, K. Faber, Curr. Opin. Chem.
Biol. 2004, 8, 120–126.
[14] I. Lavandera, A. Kern, V. Resch, B. Ferreira-Silva, A. Glieder, W. M. F.
Fabian, S. de Wildeman, W. Kroutil, Org. Lett. 2008, 10, 2155–2158.
[15] a) Y. Ni, J. H. Xu, Biotechnol. Adv. 2012, 30, 1279–1288; b) G. W. Huis-
man, J. Liang, A. Krebber, Curr. Opin. Chem. Biol. 2010, 14, 122–129;
c) S. M. A. D. Wildeman, T. Sonke, H. E. Schoemaker, O. May, Acc. Chem.
Res. 2007, 40, 1260–1266.
This work was financially supported by the National Natural Sci-
ence Foundation of China (No. 21472045, 21276082, 31200050,
and 21536004), Ministry of Science and Technology, P. R. China
(Nos. 2011CB710800), the Fundamental Research Funds for the
Central Universities (22A201514043), and Guangxi Key Laboratory
of Biorefinery.
Keywords: amine dehydrogenase · asymmetric catalysis ·
biotransformations · cascade reaction · chiral amines
[16] L. J. Wang, C. X. Li, Y. Ni, J. Zhang, X. Liu, J. H. Xu, Bioresour. Technol.
2011, 102, 7023–7028.
[1] D. Ghislieri, N. J. Turner, Top. Catal. 2014, 57, 284–300.
[2] a) H. Kohls, F. Steffen-Munsberg, M. Hçhne, Curr. Opin. Chem. Biol. 2014,
19, 180–192; b) P. J. Dunn, Chem. Soc. Rev. 2012, 41, 1452–1461.
[3] a) C. K. Savile, J. M. Janey, E. C. Mundorff, J. C. Moore, S. Tam, W. R.
Jarvis, J. C. Colbeck, A. Krebber, F. J. Fleitz, J. Brands, P. N. Devine, G. W.
Huisman, G. J. Hughes, Science 2010, 329, 305–309; b) F. G. Mutti, J. Sat-
tler, K. Tauber, W. Kroutil, ChemCatChem 2011, 3, 109–111.
[17] a) C. E. Paul, I. Lavandera, V. Gotor-Fernµndez, W. Kroutil, V. Gotor, Chem-
CatChem 2013, 5, 3875–3881; b) W. Stampfer, B. Kosjek, K. Faber, W.
Kroutil, J. Org. Chem. 2003, 68, 402–406; c) W. Stampfer, B. Kosjek, C.
Moitzi, W. Kroutil, K. Faber, Angew. Chem. Int. Ed. 2002, 41, 1014–1017;
Angew. Chem. 2002, 114, 1056–1059.
[18] a) J. S. Shin, B. G. Kim, Biotechnol. Bioeng. 1999, 65, 206–211; b) A. P.
Green, N. J. Turner, E. O’Reilly, Angew. Chem. Int. Ed. 2014, 53, 10714–
10717; Angew. Chem. 2014, 126, 10890–10893.
[19] M. L. Leroux, T. L. Gall, C. Mioskowski, Tetrahedron: Asymmetry 2001, 12,
1817–1823.
[4] a) E. O’Reilly, C. Iglesias, N. J. Turner, ChemCatChem 2014, 6, 992–995;
b) D. Koszelewski, I. Lavandera, D. Clay, G. M. Guebitz, D. Rozzell, W.
Kroutil, Angew. Chem. Int. Ed. 2008, 47, 9337–9340; Angew. Chem. 2008,
120, 9477–9480; c) E. O’Reilly, C. Iglesias, D. Ghislieri, J. Hopwood, J. L.
Galman, R. C. Lloyd, N. J. Turner, Angew. Chem. Int. Ed. 2014, 53, 2447–
2450; Angew. Chem. 2014, 126, 2479–2482; d) G. Shin, S. Mathew, M.
Shon, B. G. Kim, H. Yun, Chem. Commun. 2013, 49, 8629–8631; e) D.
Koszelewski, D. Clay, D. Rozzell, W. Kroutil, Eur. J. Org. Chem. 2009,
2289–2292; f) T. Sehl, H. C. Hailes, J. M. Ward, R. Wardenga, E. von
Lieres, H. Offermann, R. Westphal, M. Pohl, D. Rother, Angew. Chem. Int.
Ed. 2013, 52, 6772–6775; Angew. Chem. 2013, 125, 6904–6908.
Received: July 16, 2015
Published online on October 22, 2015
ChemCatChem 2015, 7, 3838 – 3841
www.chemcatchem.org
3841
ꢀ 2015 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim