Page 5 of 6
The Journal of Organic Chemistry
1H, 13C, and 31P NMR spectra of all compounds, chiral GC, HPLC
and SFG analyses of the catalytic reactions, and crystallographic
data for compound (S,S)-9 (CIF).
obtained (150.0 mg, 77% isolated yield) as a white solid. M.p.
185.0 ˚C. H NMR (500 MHz, CDCl ) δ: 7.55 (d, J = 7.1 Hz,
3
1H), 7.31-7.18 (m, 6H), 4.80 (q, J = 7.2 Hz, 1H), 4.43-4.37
(m, 1H), 4.12-4.04 (m, 4H), 3.18-3.07 (m, 2H), 1.32 (t, J = 7.0
Hz, 3H), 1.23 (dd, J = 7.1 Hz, 3H), 1.19 (dd, J = 17.5, 7.2 Hz,
1
1
2
3
4
5
6
7
8
9
AUTHOR INFORMATION
1
3
1
3
1
(
6
=
H) ppm. C{ H} NMR (126 MHz, CDCl
56.7 (q, J = 37.8 Hz, C=O), 135.6 (C), 129.4 (CH), 128.8
), 63.5 (d, J =
), 54.7 (CH), 41.2 (d, J
), 16.5 (d, J = 5.3 Hz, CH ), 16.4
) ppm. P{ H} NMR (202
3
) δ: 169.2 (C=O),
CH), 127.5 (CH), 115.8 (q, J = 287.6 Hz, CF
.6 Hz, CH
159.0 Hz, CH), 38.7 (CH
d, J = 5.3 Hz, CH
MHz, CDCl
δ: ppm. IR (neat): 3242, 3064, 2930, 1721, 1666, 1553,
3
2 2
), 62.7 (d, J = 6.6 Hz, CH
2
3
Author Contributions
All authors have given approval to the final version of the
manuscript.
31
1
(
3
), 15.4 (CH
3
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
) δ: 27.3 ppm. 19F{ H} NMR (470 MHz, CDCl
1
3
3
)
1
+
1
216, 1180, 1149, 1018 cm . HRMS (ESI) m/z: [M + Na]
PF Na 447.1267; Found 447.1267. 99%
=+26.9 (c = 0.41, CHCl ). HPLC conditions: Daicel
Notes
Calcd. for C17
H
24
N
2
O
5
3
2
4
The authors declare no competing financial interest.
de. [α]
D
3
Chiralpak® IC (25 cm x 0.46 cm), 90:10 n-hexane/2-propanol,
.0 mL/min, 220 nm, t (S,R) = 8.2 min, t (S,S) = 11.7 min.
tert-Butyl ((S)-1-(((S)-1-(diethoxyphosphoryl)ethyl)-
amino)-1-oxo-3-phenylpropan-2-yl)carbamate 10:
Compound 10 was prepared by following the general
procedure, starting from (15.7 mg, 0.0368 mmol),
Rh(nbd) ]BF (0.138 mg, 0.368 µmol), and ligand L1 (0.334
1
R
R
ACKNOWLEDGMENT
We thank MINECO (CTQ2017-89814-P) and the ICIQ
Foundation for financial support. L. C. thanks MINECO for a
FPI-SO predoctoral fellowship (BES-2015-071872). We are
grateful to J. Benet-Buchholz (ICIQ, BIST) for X-ray
crystallographic data. Dr. José Luis Núñez-Rico is gratefully
acknowledged for his support in the preparation of graphics. This
work was also partially supported by the National Science Centre,
Poland (NCN) grant number 2016/21/B/ST5/00115.
5
[
2
4
mg, 0.405 µmol). Compound 10 was obtained (12.1 mg, 77%
isolated yield) as colorless oil. IR and NMR data were in
agreement with those previously reported.
97% de.
25
[α]
D
=+16.6 (c = 0.60, CHCl
3
). HPLC conditions: Daicel
REFERENCES
Chiralpak® IC (25 cm x 0.46 cm), 85:15 n-hexane/2-propanol,
1.0 mL/min, 220 nm, t (S,R) = 15.2 min, t (S,S) = 26.0 min.
Diethyl ((R)-1-((S)-3-phenyl-2-(2,2,2-trifluoroacetami-
R
R
(1) For a general book and reviews, see: (a) Aminophosphonic and
do)propanamido)ethyl)phosphonate 11: Compound 11 was
prepared by following the general procedure, starting from 4
Aminophosphinic Acids: Chemistry and Biological Activity; Kukhar,
V. P.; Hudson, H. R.; Eds.; Wiley, 2000; 664 pp. (b) Mucha, A.;
Kafarski, P.; Berlicki, L. Remarkable Potential of the -
Aminophosphonate/Phosphinate Structural Motif in Medicinal
Chemistry. J. Med. Chem. 2011, 54, 5955-5980. (c) Abdou, M. M.;
El-Saeed, R. A. Potential Chemical Transformation of Phosphinic
Acid Derivatives and Their Applications in the Synthesis of Drugs.
Bioorg. Chem. 2019, 90, 103039.
(21.9 mg, 0.0518 mmol), [Rh(nbd)
µmol), and ligand ent-L1 (0.47 mg, 0.570 µmol). Compound
1 was obtained (18.2 mg, 83% isolated yield) as a white
2 4
]BF (0.19 mg, 0.518
1
1
solid. M.p. 179.1 ˚C. H NMR (400 MHz, CDCl
3
) δ: 7.67 (d, J
=
7.6 Hz, 1H), 7.52 (d, J = 8.1 Hz, 1H), 7.30-7.19 (m, 5H),
4
4
.89 (q, J = 6.7 Hz, 1H), 4.54-4.42 (m, 1H), 4.22-4.00 (m,
H), 3.21 (dd, J = 13.9, 5.9 Hz, 1H), 3.03 (dd, J = 13.9, 7.2
(2) For general reviews, see: (a) Demkowicz, S.; Rachon, J.;
Dasko, M.; Kozak, W. Selected Organophosphorus Compounds with
Biological Activity. Applications in Medicine. RSC Adv. 2016, 6,
Hz, 1H), 1.41-1.35 (m, 6H), 1.30 (t, J = 7.1 Hz, 3H) ppm.
13
1
C{ H} NMR (101 MHz, CDCl
C=O), 156.7 (q, J = 37.6 Hz, C=O), 135.5 (C), 129.5 (CH),
128.7 (CH), 127.4 (CH), 115.8 (q, J = 287.6 Hz, CF ), 63.1 (d,
J = 7.1 Hz, 2 x CH ), 54.5 (CH), 41.2 (d, J = 158.6 Hz, CH),
), 16.6 (d, J = 5.6 Hz, CH ), 16.5 (d, J = 5.6 Hz,
) ppm. P{ H} NMR (162 MHz, CDCl ) δ:
) δ: ppm. IR
3
) δ: 169.6 (d, J = 7.4 Hz,
7
101-7112. (b) Talma, M.; Maslanka, M.; Mucha, A. Recent
Developments in the Synthesis and Applications of Phosphinic
Peptide Analogs. Bioorg. Med. Chem. Lett. 2019, 29, 1031-1042.
3
2
(3) (a) Drag, M.; Pawelczak, M.; Kafarski, P. Stereoselective
3
8.6 (CH
2
3
Synthesis of 1-Aminoalkanephosphonic Acids with Two Chiral
Centers and their Activity towards Leucine Aminopeptidase. Chirality
2003, 15, S104-S107. (b) Orsini, F.; Sello, G.; Sisti, M.
Aminophosphonic Acids and Derivatives. Synthesis and Biological
Applications. Curr. Med. Chem. 2010, 17, 264-289. (c) Feng, Y.;
Park, J.; Li, S.-G.; Boutin, R.; Viereck, P.; Schilling, M. A.; Berghuis,
A. M.; Tsantrizos, Y. S. Chirality-Driven Mode of Binding of -
Aminophosphonic Acid-Based Allosteric Inhibitors of the Human
Farnesyl Pyrophosphate Synthase (hFPPS). J. Med. Chem. 2019, 62,
3
1
1
CH
3
), 15.8 (CH
3
3
1
2
7.7 ppm. 19F{ H} NMR (376 MHz, CDCl
3
(neat): 3209, 3041, 2984, 1723, 1661, 1551, 1224, 1178, 1149,
1
+
1
012 cm . HRMS (ESI) m/z: [M + H] Calcd. for
PF 425.1448; Found 425.1432. 99% de.
=.71 (c = 0.92, CHCl ). HPLC conditions: Daicel
Chiralpak® IC (25 cm x 0.46 cm), 90:10 n-hexane/2-propanol,
.0 mL/min, 220 nm, t (S,R) = 8.2 min, t (S,S) = 11.7 min.
C
17
H
25
4
N
2
O
5
3
2
[α]
D
3
1
R
R
9
691-9702.
(4) (a) Xie, J.-H.; Zhu, S.-F.; Zhou, Q.-L. Transition Metal-
Catalyzed Enantioselective Hydrogenation of Enamines and Imines,
Chem. Rev. 2011, 111, 1713-1760. (b) Gopalaiah, K.; Kagan, H. B.
Use of Non-functionalized Enamides and Enecarbamates in
Asymmetric Synthesis, Chem. Rev. 2011, 111, 4599-4657. (c) Ager,
D. J.; de Vries, A. H. M.; de Vries, J. G. Asymmetric homogeneous
hydrogenations at scale, Chem. Soc. Rev. 2012, 41, 3340-3380. (d)
Etayo, P.; Vidal-Ferran, A. Rhodium-catalysed Asymmetric
Hydrogenation as a Valuable Synthetic Tool for the Preparation of
ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/XXXXXXXXXX.
5
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