Advanced Synthesis & Catalysis
10.1002/adsc.202000798
open to air for substrates 1a,b,d, and the reaction stopped
C), 135.1 (CH), 144.9 (C), 147.9 (CH), 153.7 (C) ppm.
19
3
by addition of an aqueous NaOH solution (4 M, 200 µL for
8
F-NMR (THF-d , 282.35 MHz): –78.53 (d, JHF = 7.1
20
1
a,b,d; 1 M, 100 µL for 1e,f). The mixture was extracted
D
Hz) ppm. [α] = +21.8. [c 0.4, MeOH, >99% ee (S,R)-8e].
with EtOAc (3 x 500 µL), and then combined organic
phases washed with water (500 µL), dried over Na
analyzed by GC and/or HPLC.
2 4
SO
1
1
-[6-(1-Aminoethyl)pyridin-2-yl]-2,2,2-trifluoroethan-
1
-ol (8f). White solid (27 mg, 90%). Mp: 92-94 ºC. H-
NMR (CDCl
3
, 300.13 MHz): 1.46 (d, JHH = 6.6 Hz, 3H),
Typical procedure for the synthesis of amino alcohols
a,b,d-f through a concurrent cascade approach in
3.92 (brs, 3H), 4.24 (q, JHH = 6.6 Hz, 1H), 5.02 (q, JHF
=
8
6.8 Hz, 1H), 7.29 (d, JHH = 7.7 Hz, 1H), 7.33 (dd, JHH = 7.8
13
semi-preparative scale. As a representative example, for
the synthesis of (R,R)-8a a solution of the diketone 1a (30
mg, 0.14 mmol) in 1,4-dioxane (175 µL, 2.5% v/v) was
added over a suspension of RasADH (15 mg) in a
phosphate buffer (100 mM, pH 7.5, total volume 3.0 mL)
containing glucose (25 mg, 0.14 mmol), GDH (0.1 mg)
3
Hz, 1H), 7.72 (t, JHH = 7.7 Hz, 1H) ppm. C-NMR (CDCl ,
2
75.5 MHz): 24.0 (CH
3
), 52.0 (CH), 71.1 (q, JCF = 31.2
1
Hz, CH), 121.0 (CH), 121.1 (CH), 124.3 (q, JCF = 283.2
19
Hz, C), 138.1 (CH), 151.3 (CH), 163.4 (C) ppm. F-NMR
3
(CDCl , 282.35 MHz): –77.82 (d, JHF = 6.7 Hz) ppm.
3
20
[α]
D
= +14.4 [c 0.5, MeOH, >99% ee (S,R)-8f].
+
and NADP (2.5 mM). After incubation of the mixture at
room temperature for 15 minutes, the ATA-024 (30 mg)
and a phosphate buffer (100 mM, pH 7.5, 7.0 mL)
i
containing PrNH
2
(1.0 M) and PLP (1 mM) were added. Acknowledgements
The mixture was shaken at 30 ºC and 250 rpm for 48 h,
maintaining the system open to air. The reaction was
stopped by addition of an aqueous NaOH 4 M solution (1
mL) and extracted with EtOAc (3 x 5 mL). Then, the
organic phases were combined and an aqueous HCl 1 M
solution (10 mL) was added. After two extractions with
EtOAc (2 x 10 mL), the aqueous phase was basified by
addition of an aqueous NaOH 10 M solution (2 mL), which
Financial support of this work by the Spanish Ministry of
Economy and Competitiveness (MINECO, CTQ2016-75752-R
project) and Asturian Regional Government (FC-GRUPIN-
IDI/2018/000181) are gratefully acknowledged. D.G.-M. thanks
also Asturian Regional Government for a predoctoral fellowship.
We would like to thank the technical support of the
Scientific‐ Technical Services of the University of Oviedo. We
also thank Prof. Wolfgang Kroutil for the donation of
overexpressed alcohol dehydrogenases and amine transaminases.
Once retired, V.G would like to thank and dedicate this paper to
all his colleagues and disciples for their support and
collaboration along his long-life scientific career.
2 4
was extracted with EtOAc (3 x 10 mL), dried over Na SO ,
and filtered. After distillation of the solvent under reduced
pressure, the amino alcohol (R,R)-8a was isolated as a
white solid (30 mg, 99% isolated yield).
1
-[4-(1-Aminoethyl)phenyl]-2,2,2-trifluoroethan-1-ol
(
8a). White solid (30 mg, 99%). Mp: 149-150 ºC (R,R);
1
1
8
52-154 ºC (R,S). H-NMR (THF-d , 300.13 MHz): 1.36
References
(
d, JHH = 6.6 Hz, 3H), 4.05 (brs, 3H), 4.12 (q, JHH = 6.6 Hz,
1
3
1
H), 4.98 (q, JHF = 7.2 Hz, 1H), 7.42 (s, 4H) ppm. C-
, 75.5 MHz): 25.5 (CH ), 52.2 (CH), 72.6
NMR (THF-d
8
3
[
1]S. M. Lait, D. A. Rankic, B. A. Keay, Chem. Rev. 2007,
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2
1
(
q, JCF = 30.9 Hz, CH), 126.3 (q, JCF = 282.4 Hz, C),
1
9
1
26.8 (2CH), 128.6 (2CH), 135.8 (C), 148.7 (C) ppm. F-
3
NMR (THF-d
8
, 282.35 MHz): –79.02 (d, JHF = 7.2 Hz)
= –14.4 [c 1, MeOH, >99% ee (R,R)-8a); –38.9
c 0.4, MeOH, >99% ee (R,S)-8a].
20
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(
D
9
Reyes, J. Etxebarria, Curr. Org. Chem. 2005, 9, 219-
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-[3-(1-Aminoethyl)phenyl]-2,2,2-trifluoroethan-1-ol1
235.
(
8b). Yellowish solid (29 mg, 95%). Mp: 86-98 ºC. H-
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8
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1
4
.29 (brs, 2H), 3.10 (brs, 1H), 4.06 (q, JHH = 6.6 Hz, 1H),
1
2327.
.97 (q, JHF = 7.2 Hz, 1H), 7.22-7.41 (m, 3H), 7.50 (s, 1H)
13
ppm. C-NMR (THF-d
8
, 75.5 MHz): 26.5 (CH
3
), 52.3
CH), 72.9 (q, JCF = 30.9 Hz, CH), 126.2 (q, JCF = 283.1
Hz, C), 126.2 (CH), 126.6 (CH), 127.1 (CH), 128.8 (CH),
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2
1
(
4
286-4311.
1
9
1
8
37.0 (C), 149.6 (C) ppm. F-NMR (THF-d , 282.35
3 20
[
5] a) E. Ricca, B. Brucher, J. H. Schrittwieser, Adv. Synth.
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MHz): –78.99 (d, JHF = 7.3 Hz) ppm. [α]
D
= +23.3 [c
0
.4, MeOH, >99% ee (S,R)-8b].
1
-[4-(1-Aminoethyl)phenyl]-2,2-difluoroethan-1-ol (8d).
1
White solid (21 mg, 75%). Mp: 116-117 ºC. H-NMR
(
(
THF-d
brs, 3H), 4.06 (q, JHH = 6.6 Hz, 1H), 4.66 (ddd, JHF = 11.4,
8
, 300.13 MHz): 1.30 (d, JHH = 6.5 Hz, 3H), 3.36
9
4
7
.9 Hz, JHH = 4.7 Hz, 1H), 5.71 (td, JHF = 56.4 Hz, JHH
=
1
3
8
.7 Hz, 1H), 7.28-7.43 (m, 4H) ppm. C-NMR (THF-d ,
2
3
5.5 MHz): 26.3 (CH ), 52.2 (CH), 73.8 (t, JCF = 24.3
1
Hz, CH), 117.9 (t, JCF = 245.0 Hz, CH), 126.6 (2CH),
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Hepworth, N. J. Turner, S. L. Flitsch, ACS Catal. 2017,
1
9
1
2
8
28.2 (2CH), 137.5 (C), 149.2 (C) ppm. F-NMR (THF-d ,
2 2
82.35 MHz): –128.42 (ddd, JFF = 280.6 Hz, JHF = 56.0
3
2
2
Hz, JHF = 9.9 Hz), –126.91 (ddd, JFF = 280.6 Hz, JHF
=
3
20
5
6.9 Hz, JHF = 11.6 Hz) ppm. [α]
99% ee (R,R)-8d].
D 3
= +4.0 [c 0.4, CHCl ,
>
1
1
-[5-(1-Aminoethyl)pyridin-2-yl]-2,2,2-trifluoroethan-
1
-ol (8e). Viscous white-yellow solid (26 mg, 88%). H-
, 300.13 MHz): 1.33 (d, JHH = 6.6 Hz, 3H),
.40 (brs, 3H), 4.15 (q, JHH = 6.6 Hz, 1H), 5.05 (q, JHF
.1 Hz, 1H), 7.51 (d, JHH = 8.1 Hz, 1H), 7.85 (dd, JHH = 8.2,
7
, 710-724; e) F. Rudroff, M. D. Mihovilovic, H.
NMR (THF-d
8
Gröger, R. Snajdrova, H. Iding, U. T. Bornscheuer, Nat.
Catal. 2018, 1, 12-22; f) S. Gandomkar, A. Żądło-
Dobrowolska, W. Kroutil, ChemCatChem, 2019, 11,
225-243.
3
7
2
=
13
.3 Hz, 1H), 8.55 (d, JHH = 2.3 Hz, 1H) ppm. C-NMR
, 75.5 MHz): 26.1 (CH ), 49.8 (CH), 73.2 (q,
CF = 30.7 Hz, CH), 122.7 (CH), 125.9 (q, JCF = 283.0 Hz,
(
THF-d
J
8
3
2
1
1
1
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