Asymmetric synthesis of novel vicinal amino alcohols via intramolecular ketone- N -sulfinylimine pinacol-type reductive coupling promoted by SmI 2

Article abstract of DOI:10.1080/00397911.2013.841938

A novel intramolecular asymmetric ketone-N-sulfinylimine pinacol-type reductive coupling reaction induced by SmI₂ was reported. A series of 1-amino-1,2,3,4-tetrahydronaphthalen-2-carbinols were obtained in moderate to good yields with excellent

Full text of DOI:10.1080/00397911.2013.841938

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Asymmetric Synthesis of Novel Vicinal
Amino Alcohols via Intramolecular
Ketone-N-sulfinylimine Pinacol-Type
Reductive Coupling Promoted by SmI2
Yun-Hui Zhao a & Han-Wen Liu a
a Key Laboratory of Theoretical Chemistry and Molecular Simulation
of Ministry of Education, Hunan Province College Key Laboratory
of QSAR/QSPR , Hunan University of Science and Technology ,
Xiangtan , China
Accepted author version posted online: 06 Nov 2013.Published
online: 24 Feb 2014.
To cite this article: Yun-Hui Zhao & Han-Wen Liu (2014) Asymmetric Synthesis of Novel Vicinal Amino
Alcohols via Intramolecular Ketone-N-sulfinylimine Pinacol-Type Reductive Coupling Promoted by SmI2
, Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 44:7, 1012-1018, DOI: 10.1080/00397911.2013.841938
To link to this article: http://dx.doi.org/10.1080/00397911.2013.841938
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Synthetic Communications1, 44: 1012–1018, 2014
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2013.841938
ASYMMETRIC SYNTHESIS OF NOVEL VICINAL AMINO
ALCOHOLS VIA INTRAMOLECULAR KETONE-N-
SULFINYLIMINE PINACOL-TYPE REDUCTIVE
COUPLING PROMOTED BY SmI2
Yun-Hui Zhao and Han-Wen Liu
Key Laboratory of Theoretical Chemistry and Molecular Simulation of
Ministry of Education, Hunan Province College Key Laboratory of QSAR=
QSPR, Hunan University of Science and Technology, Xiangtan, China
GRAPHICAL ABSTRACT
Abstract A novel intramolecular asymmetric ketone-N-sulfinylimine pinacol-type reductive
A series of 1-amino-1,2,3,4-
coupling reaction induced by SmI2 was reported.
tetrahydronaphthalen-2-carbinols were obtained in moderate to good yields with excellent
ee and high dr.
[Supplementary materials are available for this article. Go to the publisher’s online
edition of Synthetic Communications1 for the following free supplemental resource(s):
Full experimental and spectral details.]
Keywords Asymmetric synthesis; N-sulfinylimine; samarium diiodide; vicinal amino
alcohol
INTRODUCTION
Vicinal amino alcohols are common structures found in natural products.[1]
The amino alcohols are also important building blocks for organic and pharmaceu-
tical synthesis.[2] Moreover, 1,2-amino alcohols have been utilized as excellent chiral
Received July 4, 2013.
Address correspondence to Yun-Hui Zhao, Key Laboratory of Theoretical Chemistry and
Molecular Simulation of Ministry of Education, Hunan Province College Key Laboratory of QSAR=
QSPR, Hunan University of Science and Technology, Xiangtan 411201, China. E-mail: zyh00041130@
163.com
1012

VICINAL AMINO ALCOHOLS
1013
Figure 1. Representative bioactive molecular and chiral ligands possessing vicinal amino alcohol structure.
ligands and auxiliaries for asymmetric synthesis.[3] 1-Amino-2-hydroxytetrahydro-
naphthalene is a unique vicinal amino alcohol structures whose derivatives exhibit
significant anorexigenic and anti-amastigote activity (I, II, Fig. 1).[4] Furthermore,
these compounds have been applied to catalyze Reformatsky-type reaction and
reduction of ketone as the chiral auxiliary (III, IV, Fig. 1).[5]
Several approaches have been reported for preparation of optically pure
1-amino-2-hydroxytetrahydronaphthalene by employing 1,2-dihydronaphathalene
as starting material.[6] SmI2-promoted[7] pinacol-type aldehyde–imine reductive
coupling reaction is one of the most useful methods for the construction of two
new chiral carboncenters, and many efforts have been devoted to develop this
methodology.[8] The Lin group has also made great improvements to the synthesis
of highly enantioselective b-amino alcohols[9] via cross coupling of aldehydes
with N-tert-butanesulfinyl imines.[10] There have been few reports of asymmetric syn-
thesis of 1,2-amino tertiary-carbinol induced by SmI2, except for two examples of
ketone-sulfinimine coupling reactions.[11] Therefore, development of methods
for the asymmetric synthesis of 1-amino-1,2,3,4-tetrahydronaphthalen-2-tertiary-
carbinols is desirable. In this situation, we envisioned that intramolecular
asymmetric ketone–sulfinimine coupling would provide access to 1-amino-1,2,3,4-
tetrahydronaphthalen-2-tertiary-carbinols with high optical purity. Herein we report
our studies using this strategy.
RESULTS AND DISCUSSION
We began our investigation by examining the reaction of compound (R)-N-tert-
butanesulfinyl imine 1a induced by SmI2 at ꢀ78 ꢁC. Product was observed in traces,
and most of the materials were recovered. Perhaps the ketyl radical anion was difficult
to form upon single-electron reduction of benzoyl because of the stability of the struc-
ture. Then the reaction was carried out at room temperature. To our delight, the tar-
get compound was obtained in 20% yield. The yield of this product increased to 50%
when 300% of SmI2 was employed. With this promising result, the reaction conditions
were then optimized with regard to the additive and the proton source. The addition
of tertiary butyl alcohol could not improve this reaction (entry 5, Table 1). It was also
found that the reaction of 1a did not require hexamethylphosphoramide (HMPA)
and other Lewis acids (entries 7 and 8, Table 1). Fortunately, the product was
obtained as a single diastereoisomer under all reaction conditions with up to 98% ee.
The low activity of the carbonyl of substrate 1a may cause the poor yield of this
reaction. The phenyl group was replaced by methyl, and the yield of this reaction

1014
Y.-H. ZHAO AND H.-W. LIU
Table 1. Optimization of reaction conditionsa
Entry
Temp (ꢁC)
SmI2 (eq)
Additive
Yield (%)b
1
2
3
4
5
6
7
8
ꢀ78
Rt
Rt
0
2
2
3
3
3
3
3
3
—
—
Trace
20
50
—
—
23
15
Rt
Rt
Rt
Rt
t-BuOH (2 eq)
HMPA (2 eq)
NiI2 (5%)
LiCl (2 eq)
47
38
22
aAll reactions were reacted for 3 h.
bIsolated yield of the single diastereoisomer.
increased to 86%. The ee value of the main diastereoisomer was up to 97%, though
the dr value was decreased to 3:1 (entry 2, Table 2). Under the optimum condition,
we probed the scope and the limitation of this reductive coupling reaction (Table 2).
Both aryl and alkyl ketones gave moderate to excellent yields. The reaction of aryl
Table 2. Intramolecular asymmetric ketone-imine coupling reaction
Entry
Substrate
R
Product
dra
Yield (%)b
1
2
3
4
5
6
7
8
9
1a
1b
1c
1d
1e
1f
Ph
Me
2a
2b
2c
2d
2e
2f
>99:1
3:1
50
86
35
37
63
81
63
74
91
4-MePh
3-MePh
Cyclohexanyl
Cyclopentyl
Bn
>99:1
>99:1
6:1
9:1
1g
1h
1i
2g
2h
2i
>99:1
>99:1
6:1
Isobutyl
Isopropyl
adr was determined by 1H NMR of the crude products.
bIsolated yields of all diastereomers.

VICINAL AMINO ALCOHOLS
1015
Figure 2. X-ray crystal structure of the intramolecular coupling product 2e. (Figure is provided in color
online.)
ketones gave a lower yield but with high dr, and the reaction of alkyl ketones with
hindered group may provide good dr (entries 7 and 8, Table 2). The stereochemistry
of the two newly formed carbon centers of vicinal amino alcohol 2e was determined
to be (S, R)-configuration by x-ray crystallography (Fig. 2).
The intramolecular chiral N-tert-butanesulfinyl imine–ketone coupling reac-
tion was applied to synthesis of chrome vicinal amino alcohol. The starting material
salicylaldehyde reacted with x-bromoacetophenone to provide compound 4. Then
Scheme 1. Synthesis of tetrahydronaphthalen vicinal amino alcohol.
Scheme 2. Preparation of chrome-amino alcohol.

1016
Y.-H. ZHAO AND H.-W. LIU
the N-tert-butanesulfinyl imine 5 was obtained from 4 and N-tert-butanesulfinamide
in the presence of KHSO4. The substrate 5 was reacted under SmI2 reaction
condition to afford chrome vicinal amino tertiary-carbinol 6 in 53% yield as a single
diastereoisomer (Scheme 2).
CONCLUSION
In conclusion, we have developed a simple method for the preparation of
optically pure 1-amino-1,2,3,4-tetrahydronaphthalen-2-ols by the SmI2-induced
intramolecular reductive coupling of ketone-sulfinimines. This is the first successful
example of highly diastereoselective and enantioselective synthesis of 1-amino-1,
2,3,4-tetrahydronaphthalen-2-ols via forming two new chiral carbon centers simul-
taneously. It provides a straightforward access to enantiopure tetrahydronaphthalen
1,2-amino-alcohols, which are widely used in asymmetric synthesis. Potential appli-
cations of this protocol along with its products in asymmetric synthesis are currently
under investigation.
EXPERIMENTAL
Analytical thin-layer chromatography (TLC) was carried out on precoated
silica-gel plates. Column chromatography was conducted with 300 to 400-mesh silica
1
gel. NMR spectra were recorded at 400 MHz for H NMR using SiMe4 as an inter-
nal standard in CDCl3 and 100 MHz for 13C NMR. Enantiomeric excesses were
determined by chiral high-performance liquid chromatography (HPLC) analysis.
Optical rotations were measured on a Jasco 1030 polarimeter. Tetrahydrofuran
(THF) was freshly distilled from sodium.
A solution of 1a (0.2 mmol) in THF (2 mL) was added dropwise to a solution of
SmI2 (0.6 mmol) in THF (3 mL) under Ar, and the mixture was stirred at room tem-
perature until all starting material has been consumed. The reaction was quenched
by saturated Na2S2O3 (3 mL) and diluted with ethyl acetate, and the aqueous phase
was extracted with ethyl acetate. The combined organic layer was dried (Na2SO4),
filtered, and concentrated. The residue was purified by silica-gel flash column
chromatography to afford product 2a, (R)-N-((1S,2R)-2-hydroxy-2-phenyl-1,2,3,
24
4-tetrahydronaphthalen-1-yl)-tert-butylsulfinamide. [a]D þ 60.8 (c 0.99, CHCl3).
Colorless oil, 1H NMR (400 MHz, CDCl3) d 7.60–7.58 (m, 1H), 7.42 (d, 2H,
J ¼ 8.0 Hz), 7.32 (t, 2H, J ¼ 8.0 Hz), 7.28–7.25 (m, 3H), 7.21–7.18 (m, 1H), 4.66
(d, 1H, NH, J ¼ 6.8 Hz), 3.32 (d, 1H, J ¼ 6.8 Hz), 3.10–3.03 (m, 2H), 2.88 (dt, 1H,
J ¼ 16.8 Hz, 4.8 Hz), 2.46–2.39 (m, 1H), 2.28–2.22 (m, 1H), 0.96 (s, 9H); 13C NMR
(100 MHz, CDCl3) d 144.8, 136.8, 136.1, 129.6, 128.5, 128.4, 127.7, 127.6, 127.0,
126.6, 75.4, 63.5, 56.3, 31.7, 26.1, 22.8; IR (KBr, v=cmꢀ1): 3371, 3241, 3059, 2928,
2864, 1612, 1495, 1448, 1042 cmꢀ1; HRMS (ESI) 366.1509 [MþNa]þ calculated
for C20H25NO2SNaþ 366.1504. The enantiomeric ratios was determined by HPLC
analysis of the acetamide, obtained by deprotection and then protected by acetyl
group, using a Chiracel OD-H column (22 ꢁC, 214 nm, 70:30 hexane=2-propanol,
1 mL=min); tminor ¼ 5.4 min and tmajor ¼ 7.3 min, 98% ee.
Complete experimental details are available online in the Supplemental
Material.

VICINAL AMINO ALCOHOLS
1017
FUNDING
The generous financial support from the National Natural Science Foundation of
China (Nos. 2097104 and 20672135) and the National Natural Science Foundation
of Hunan (11JJ3016) is gratefully acknowledged.
REFERENCES
1. (a) Wang, Z.-M.; Kolb, H. C.; Sharpless, K. B. J. Org. Chem. 1994, 59, 5104; (b)
Bergmeier, S. C. Tetrahedron 2000, 56, 2561; (c) Mahler, G.; Serra, G.; Manta, E. Synth.
Commun. 2005, 35, 1481; (d) Burchak, O. N.; Py, S. Tetrahedron 2009, 65, 7333.
2. (a) Radesca, L.; Bowen, W. D.; Di Paolo, L. D.; Costa, B. R. J. Med. Chem. 1991, 34,
3058; (b) Dorsey, B. D.; Levin, L. B.; McDaniel, S. L.; Vacca, J. P.; Guare, J. P.; Darke,
P. L.; Zugay, J. A.; Emini, E. A.; Schleif, W. A.; Quintero, J. C.; Lin, J. H.; Chen, I. W.;
Holloway, M. K.; Fitzgerald, P. M. D.; Axel, M. G.; Ostovic, D.; Anderson, P. S.; Huff, J.
R. J. Med. Chem. 1994, 37, 3443; (c) Vacca, J. P.; Dorsey, B. D.; Schleif, W. A.; Levin, R.
B.; McDaniel, S. L.; Darke, P. L.; Zugay, J.; Quintero, J. C.; Blahy, O. M.; Roth, E.;
Sardana, V. V.; Schlabach, A. J.; Graham, P. J.; Condra, J. H.; Gotlib, L.; Holloway,
M. K.; Lin, J.; Chen, I.-W.; Vastag, K.; Ostovic, D.; Ardenson, P. S.; Emini, E. A.; Huff,
J. R. Proc. Nat. Acad. Sci. U.S.A. 1994, 91, 4096; (d) Roxburgh, C. J. Synthesis 1996, 307;
(e) Condra, J. H. Drug. Resist. Updates 1998, 1, 292; (f) Markowits, M. Antimicrob. Agents
Chemother. 1998, 42, 2775; (g) Hogarth, J.; Lloyd, D. G. J. Antimicrob. Chemother. 2000,
46, 625.
3. (a) Ager, D. J.; Prakash, I.; Schaad, D. R. Chem. Rev. 1996, 96, 835; (b) Davies, I. W.; Gerena,
L.; Lu, N.; Larsen, R. D.; Reider, P. J. J. Org. Chem. 1996, 61, 9629; (c) Palmieri, G. Eur.
J. Org. Chem. 1999, 4, 805; (d) Pu, L.; Yu, H.-B. Chem. Rev. 2001, 101, 757; (e) Nugent,
W. A. Org. Lett. 2002, 4, 2133–2136; (f) Binanzer, M.; Hsieh, S.-Y.; Bode, J. W. J. Am. Chem.
Soc. 2011, 133, 19698.
4. (a) Bhandari, K.; Srivastava, S.; Shanker, G. Bioorg. Med. Chem. 2004, 12, 4189; (b)
Thibeault, D.; Roy, J.; DeRoy, P.; Poirier, D. Bioorg. Med. Chem. 2008, 16, 5062; (c)
Marrapu, V. K.; Srinivas, N.; Mittal, M.; Shakya, N.; Gupta, S.; Bhandari, K. Bioorg.
Med. Chem. Lett. 2009, 21, 1407.
5. (a) Bellucci, G. M.; Bergamini, A.; Cozzi, P. G.; Papa, A.; Tagliavini, E.; Umani-Ronchi,
A. Tetrahedron: Asymmetry 1997, 8, 895; (b) Orsini, F.; Sello, G.; Manzo, A. M.; Lucci, E.
M. Tetrahedron: Asymmetry 2005, 16, 1913.
6. (a) Lakshman, M. K.; Zajc, B. Tetrahedron Lett. 1996, 37, 2529; (b) Higashijima, S.; Itoh,
H.; Senda, Y.; Nakano, S. Tetrahedron: Asymmetry 1997, 8, 3107; (c) Lakshman, M. K.;
Chaturvedi, S.; Zajc, B.; Gibson, D. T.; Sol, M.; Resnick, S. M. Synthesis 1998, 1352; (d)
Cho, B. T.; Choi, O. K. Bull. Korean Chem. Soc. 2001, 22, 1261; (e) Recuero, V.; Gonzalo,
G.; Brieva, R.; Gotor, V. Eur. J. Org. Chem. 2006, 11, 4224; (f) Kozhushkov, S. I.; Yufit,
D. S.; Meijere, A. Adv. Synth. Catal. 2005, 347, 255.
7. For reviews, see (a) Molander, G. A.; Harris, C. R. Chem. Rev. 1996, 96, 307; (b) Krief,
A.; Laval, A.-M. Chem. Rev. 1999, 99, 745; (c) Kagan, H. B. Tetrahedron 2003, 59, 10351;
(d) Edmonds, D. J.; Johnson, D.; Procter, D. J. Chem. Rev. 2004, 104, 3371.
8. (a) Taniguchi, N.; Uemura, M. J. Am. Chem. Soc. 2000, 122, 8301; (b) Uemura, M. Org.
Lett. 2002, 835–838; (c) Zhong, Y.-W.; Izumi, K.; Xu, M.-H.; Lin, G.-Q. Org. Lett. 2004,
6, 4747; (d) Zhong, Y.-W.; Xu, M.-H.; Lin, G.-Q. Org. Lett. 2004, 6, 3953; (c) Zhong,
Y.-W.; Dong, Y.-Z.; Fang, K.; Izumi, K.; Xu, M.-H.; Lin, G.-Q. J. Am. Chem. Soc.
2005, 127, 11956.
9. Zhong, Y.-W. Dong, Y.-Z., Fang, K., Izumi, K., Xu, M.-H., Lin, G.-Q. J. Am. Chem.
Soc. 2005, 127, 11956.

1018
Y.-H. ZHAO AND H.-W. LIU
10. (a) Liu, G.; Cogan, D. A.; Owens, T. D.; Tang, T. P.; Ellman, J. A. J. Org. Chem. 1999,
64, 1278; (b) Ellman, J. A.; Owens, T. D.; Tang, T. P. Acc. Chem. Res. 2002, 35, 984;
(c) Lin, G.-Q.; Xu, M.-H.; Zhong, Y.-W.; Sun, X.-W. Acc. Chem. Res. 2008, 41, 831;
´
(d) Ferreira, F.; Botuha, C.; Chemla, F.; Perez-Luna, A. Chem. Soc. Rev. 2009, 38, 1162.
11. (a) Lin, X.; Bentley, P. A.; Xie, H. Tetrahedron Lett. 2005, 46, 7849; (b) Wang, B.; Wang,
Y.-J. Org. Lett. 2009, 11, 3410.