Preparation of enantiomerically pure 2-(1′-aminomethyl)furan derivatives and synthesis of an unnatural polyhydroxylated piperidine

Article abstract of DOI:10.1016/j.tetlet.2005.09.189

Zinc-mediated propargylation of α-acylaminoaldehydes, and subsequent oxidative isomerization followed by Ag(I)-catalyzed cycloisomerization conveniently provides a new enantioselective route to the corresponding 2-aminoalkylfurans. One of these furans was

Full text of DOI:10.1016/j.tetlet.2005.09.189

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 8567–8571
Preparation of enantiomerically pure 2-(10-aminomethyl)furan
derivatives and synthesis of an unnatural
polyhydroxylated piperidine
Xin Cong,a,b Ke-Gang Liu,b Qing-Jiang Liaoa and Zhu-Jun Yaob,*
aDepartment of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang Road, Nanjing 210009, China
bState Key Laboratory of Bioorganic and Natural Product Chemistry, Shanghai Institute of Organic Chemistry,
Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China
Received 15 August 2005; revised 28 September 2005; accepted 30 September 2005
Available online 14 October 2005
Abstract—Zinc-mediated propargylation of a-acylaminoaldehydes, and subsequent oxidative isomerization followed by Ag(I)-cat-
alyzed cycloisomerization conveniently provides a new enantioselective route to the corresponding 2-aminoalkylfurans. One of these
furans was successfully converted into an unnatural polyhydroxylated piperidine that efficiently incorporated structural features of
the starting material. This represents a new entrance to biologically interesting polyhydroxylated piperidines having diverse
substitutions.
Ó 2005 Elsevier Ltd. All rights reserved.
Synthesis of furan derivatives has attracted tremendous
interest over the past century, reflecting both the impor-
tance of these heterocycles in natural and synthetic
substances and a requirement for more selective and
versatile approaches for their syntheses.1 Furthermore,
optically active 2-(10-amino-10-substituent-methyl)fur-
ans serve as important synthetic building blocks for
a variety of biologically important molecules. For
example, 2-amino-2-(2-furyl)ethan-1-ol (1) is a critical
intermediate for the synthesis of polyhydroxylated
piperidines,2 including (+)-desoxoprosophylline,3 and
(+)-6-epicastanospermine (Scheme 1).4 Moreover, the
furan moiety of 2-amino-2-(2-furyl)ethan-1-ol is also a
more potent pharmacophore than the corresponding
phenyl group in natural paclitaxel.5
OH
OH
HO
OH
OH
R=H
*
*
R
O
NH2
N
H
1
Polyhydroxylated piperidine
OH
R=COOEt
OH
OH
H
HO
HO
OH
C12H25
N
N
H
(+)-6-Epicastanospermine (+)-Desoxoprosophylline
Scheme 1. Several structures with 2-amino-2-(2-furyl)ethan-1-ol
moiety.
Today, most synthetic approaches toward 2-(10-amino-
20-hydroxyalkyl)furans (1, R = H) utilize materials con-
taining functionalized furans. Among these, a variety of
protocols to elaborate the side chains attached to the
furan ring with the desired stereochemistry have been
reported, including Sharpless asymmetric dihydroxyla-
tion2,6 or aminohydroxylation7 of vinylfuran; reduction
of the carboxyl group from furyl glycine;8 oxazaboroli-
dine-catalyzed enantioselective reduction of oximes or
oxime ethers,9 and nucleophilic substitution of 2-furyl
glycol leading to azides.10 Vicinal amino alcohols are
also very useful chiral building blocks for the syntheses
of a variety of biologically active compounds,11 and a
number of synthetic methods have used these in the
construction of chiral furans. For example, a one-pot
reaction of aldehyde, amine, and furyl organo-
boronic acid directly furnished the corresponding chiral
2-amino-2-(2-furyl)ethan-1-ol derivatives.12 Both syn-
and anti-b-amino alcohols were achieved through
catalytic diastereo- and enantioselective Mannich-type
*
Corresponding author. Tel.: +86 21 5492 5133; fax: +86 21 6416
6128; e-mail: yaoz@mail.sioc.ac.cn
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.09.189

8568
X. Cong et al. / Tetrahedron Letters 46 (2005) 8567–8571
NH2
no-2-(furan-20)-yl-ethanols using L- or D-serine as a
R
*
*
common starting material. We include the application
of these furan derivatives to the synthesis of diverse
unnatural polyhydroxylated piperidines.
OH
O
Cycloisomerization
Oxidation
NHBoc
BocN
O
O
As illustrated in Figure 1, a pivotal transformation for
furan formation is envisioned to be a cycloisomerization
of a-allenylketones.1,18 The requisite allenylketones
can be synthesized by oxidation and subsequent in situ
isomerization of the corresponding homopropargyl
alcohols. Preparation of the homopropargyl alcohols
can be carried out by propargylation of aldehyde
precursor and/or diastereoselective addition of RMgBr
(R = phenyl, n-butyl, vinyl) to Garner aldehyde.19,20
R
*
R=Phenyl
n-Butyl
*
*
R=H
O
OMOM
O
Vinyl
NHBoc
BocN
R
*
*
*
OH OMOM
OH
Propargylation
Our synthesis of (S)-2-amino-2-(furan-20-yl)ethan-1-ol
(2) started from commercially available L-serine, which
gave the protected aminodiol 3 in high yield (Scheme
2). Swern oxidation gave the Garner aldehyde,21 which
was treated with propargyl bromide and zinc dust in
DMF and Et2O (1:1, v/v) to afford 4 in excellent yield.
Dess–Martin oxidation of alcohol 4 and in situ isomer-
ization furnished a-allenylketone 5 quantitively. Cyclo-
isomerization of allenone 5 was achieved in the
presence of catalytic AgNO3 under an inert atmosphere
to afford the furan derivative 6 (96% ee as measured by
HPLC). Global deprotection of 6 with 3 N HCl in meth-
NHBoc
NBoc
Serine
R
*
O
*
OHC
*
CHO
OMOM
NBoc
O
R
*
diastereoselective
addition
*
OMOM
Figure 1. Retrosynthetic analysis of 2-amino-2-(furan-20-yl)ethanols.
reactions.13 Addition of racemic allylic stannanes to
N-acyliminium precursors14 or addition of the chloro-
titanium enolate of methyl methoxyacetate to relatively
unactivated aldimines15 represent alternative appro-
aches for these vicinal amino alcohols. Recently, interest
in basic research and biomedical investigations has
continued to mount in the area of new applications of
natural and unnatural glycosidase inhibitors.16 Many
deoxy azasugars have been synthesized and shown to in-
hibit oligosaccharide processing enzymes selectively.17
For these targets, including the polyhydroxylated piperi-
dines and their derivatives, a-furfuryl amines are ideal
starting materials.4 In this report, we detail an efficient
and enantioselective route for the synthesis of 2-ami-
anol followed by treatment with K2CO3 afforded (S)-2-
23
amino-2-(furan-20)yl-ethanol (2, ½aꢀD ꢁ10.9 (c 0.9,
20
CH3OH); Ref. 9: ½aꢀD ꢁ7.4 (c 0.8, CH3OH)) in high
yield after purification by silica gel flash column chro-
matography (ethyl acetate/hexane/methanol = 1:1:1).9
This synthesis has the advantages of inexpensive materi-
als, ease of operation, good overall yield, and high
enantioselectivity.
As essential structural components of several biolo-
gically active compounds, b-amino alcohols have
ref. 19
a-d
e, f
NBoc
L-Serine
O
OH
97%
81% over 4 steps
3
g
NBoc
NBoc
NBoc
h
O
O
O
75%
91%
O
OH
O
4
5
6
ee=96%
NH
NH2
2 HCl
j
i
HO
HO
96%
90%
O
7
O
2
NBoc
O
D
-Serine
O
8
ee=98%
Scheme 2. Reagents and conditions: (a) HCl, MeOH, reflux; (b) Boc2O, Et3N, THF; (c) 2,2-DMOP, BF3ÆEt2O, acetone; (d) LAH, anhydrous THF,
ꢁ10 °C; (e) DMSO, (COCl)2, Et3N, CH2Cl2, ꢁ78 °C; (f) C3H3Br, Zn (dust), DMF/Et2O (1:1, v/v); (g) Dess–Martin periodinane, CH2Cl2; (h) AgNO3
(20mol %), acetone, reflux; (i) 3 N HCl/CH 3OH; (j) K2CO3, CH3OH. The ee values were determined by HPLC: Chiralpak OJ, eluent hexane/
isopropanol 95:5, flow rate 0.7 mL/min.

X. Cong et al. / Tetrahedron Letters 46 (2005) 8567–8571
8569
attracted the attention of many synthetic chemists.
Among recent literature,11,22 1,2-diphenyl-2-aminoetha-
nols having both syn- and anti-configurations have
shown great value because of their potential use in
asymmetric synthesis as chiral auxiliaries or chiral
ligands.23 Utilizing the methodology outlined above,
further development of general and efficient routes was
desired to more diverse 1-aryl-2-amino-2-(furan-2-
yl)ethanols, which would allow the asymmetric synthesis
to exploit effects caused by the aromaticity of the furan
moiety.
14b using AgNO3 as a catalyst followed by global depro-
tection of the resulting furan 15 (95% ee, measured by
HPLC) with 3 N HCl in methanol afforded (1R,2R)-1-
phenyl-2-amino-2-(furan-20)-yl-ethanol 9 in excellent
overall yield.
Similarly, two additional 2-aminoethanol derivatives,
(1R,2R)-1-amino-1-(furan-2-yl)but-3-en-2-ol (23) and
(1R,2R)-1-amino-1-(furan-2-yl)hexan-2-ol (30) were
synthesized from alcohol 3. The separation of diastereo-
mers (22a/22b and 29a/29b) was achieved by column
chromatography following furan formation (ratio of
17: anti:syn = 59:14; ratio of 24: anti:syn = 68:22,
respectively26,27) (Scheme 4). In theory, any 1-substi-
tuted-2-amino-2-(20-furan)-yl-ethan-1-ol could be pre-
pared by this general route.
Accordingly, (1R,2R)-1-phenyl-2-amino-2-(furan-2-yl)-
ethanol hydrochloride (9) was synthesized from Garner
alcohol 3 (Scheme 3). Treatment of freshly prepared
L-Garner aldehyde with phenylmagnesium bromide
(3.0equiv) in anhydrous THF at ꢁ70to 0 °C gave 10
as a mixture of diastereoisomers.24 The newly produced
hydroxyl group was then protected as its MOM ether
and the N,O-acetal was selectively deprotected with a
catalytic amount of bismuth(III) bromide in acetoni-
trile.25 Dess–Martin oxidation of the exposed primary
alcohol 12 in CH2Cl2, followed by propargylation with
zinc dust and propargyl bromide afforded homopropar-
gyl alcohol 13. Following Dess–Martin oxidation of the
diastereomeric mixture 13, syn-allenyl ketone 14a and
anti-allenyl ketone 14b were easily separated by silica
gel column chromatography in 19% and 77% yield,
respectively. This indicated that the previous diastereo-
selective Grignard addition to the Garner aldehyde gave
the anti-adduct predominantly (anti:syn = 77:19).20,24
As before, cycloisomerization of the major product
With the furan derivative 15 in hand, construction of
unnatural piperidines was investigated next (Scheme
5). Oxidation of 15 using m-CPBA gave the dihydropyri-
done 31, whose hemi-aminal hydroxyl group was imme-
diately masked as an ethoxyl group using triethyl
orthoformate and BF3ÆOEt2. Ketone 32 was then
reduced stereoselectively by NaBH4 in the presence of
CeCl3Æ7H2O4,28 to give 33 as the sole product, whose
absolute configuration was confirmed by NOESY stud-
ies on the final target 36. Reductive removal of ethoxyl
group of 33 by NaBH4 in formic acid provided com-
pound 34. Substrate-controlled dihydroxylation29 of 34
with a catalytic amount of OsO4 and NMO furnished
triol 35 as a single diastereomer. Global deprotection
of 35 using 3 N HCl/MeOH afforded the enantiopure
NBoc
NBoc
NBoc
c
a,b
O
O
O
OH
81%
81%
3
OH
10
OMOM
11
(from
d
L
-Serine)
HO
NHBoc
NHBoc
g
e,f
HO
MOMO
13
94%
92%
MOMO
12
NHBoc
NHBoc
NHBoc
h
+
O
O
O
74%
MOMO
MOMO
MOMO
15
14a:19%
14b:77%
ee=95%
NH
NH2
2 HCl
i
*
*
O
97%
HO
HO
9
2-amino-1,2-diphenylethanol
NHBoc
O
D
-Serine
MOMO
16
ee=97%
Scheme 3. Reagents and conditions: (a) DMSO, (COCl)2, Et3N, CH2Cl2, ꢁ78 °C; (b) PhMgBr, THF, ꢁ70to 0 °C; (c) MOMCl, DIPEA, CH2Cl2; (d)
BiBr3 (20mol %), CH 3CN; (e) Dess–Martin periodinane, CH2Cl2; (f) C3H3Br, Zn (dust), DMF/Et2O (1:1, v/v); (g) Dess–Martin periodinane,
CH2Cl2; (h) AgNO3 (20mol %), acetone, reflux; (i) 3 N HCl/CH 3OH. The ee values were determined by HPLC: Chiralpak AD, eluent hexane/
isopropanol 90:10, flow rate 0.7 mL/min.

8570
X. Cong et al. / Tetrahedron Letters 46 (2005) 8567–8571
and excellent enantio purity of products. These optically
NBoc
NBoc
NBoc
pure furyl aminoethanols may potentially serve as chiral
ligand or chiral auxiliary in asymmetric synthesis, and as
intermediates for the syntheses of diverse unnatural
polyhydroxylated alkaloids.
a,b
c
d
O
O
O
OH
R
R
OH
17 (70%)
24 (82%)
OMOM
18 (78%)
25 (80%)
3
HO
NHBoc
e,f
NHBoc
R
NHBoc
g
h
Acknowledgments
R
HO
O
R
MOMO
MOMO
MOMO
This work was financially supported in part by the
Major State Basic Research and Development Program
(G2000077500), NSFC (20425205 and 20321202), the
Chinese Academy of Sciences (KGCX2-SW-209) and
Shanghai Municipal Commission of Science and Tech-
nology (03DZ19203 and 04DZ14901).
19 (98%)
26 (81%)
20 (98%)
27 (96%)
21 (81%)
28 (85%)
HCl
NH2
NHBoc
NHBoc
i
17-23:
+
R
O
O
O
R
R
R = -CH=CH2
MOMO
22b (59%)
29b (68%)
HO
23 (96%)
30 (97%)
MOMO
22a (14%)
29a (22%)
24-30:
R = -C4H9
n
References and notes
Scheme 4. Reagents and conditions: (a) DMSO, (COCl)2, Et3N,
CH2Cl2, ꢁ78 °C; (b) vinylMgBr (for compound 17) or n-butylMgBr
(for compound 24), THF, ꢁ70to 0 °C; (c) MOMCl, DIPEA, CH2Cl2;
(d) BiBr3 (20mol %), CH 3CN; (e) Dess–Martin periodinane, CH2Cl2;
(f) C3H3Br, Zn (dust), DMF/Et2O (1:1, v/v); (g) Dess–Martin
periodinane, CH2Cl2; (h) AgNO3 (20mol %), acetone, reflux; (i) 3 N
HCl/CH3OH.
1. Brown, R. C. D. Angew. Chem., Int. Ed. 2005, 44, 850–
852.
2. Zhou, W.-S.; Lu, Z.-H.; Wang, Z.-M. Tetrahedron 1993,
49, 2641–2654.
3. Yang, C.-F.; Xu, Y.-M.; Liao, L.-X.; Zhou, W.-S.
Tetrahedron Lett. 1998, 39, 9227–9228.
4. Zhang, H.-X.; Xia, P.; Zhou, W.-S. Tetrahedron 2003, 59,
2015–2020.
5. (a) Georg, G. I.; Harriman, G. C. B.; Hepperle, M.;
Clower, J. S.; Vander Velde, D. G. J. Org. Chem. 1996, 61,
2664–2676; (b) Altstadt, T. J.; Fairchild, C. R.; Golik, J.;
Johnston, K. A.; Kadow, J. F.; Lee, F. Y.; Long, B. H.;
Rose, W. C.; Vyas, D. M.; Wong, H.; Wu, M.-J.;
Wittman, M. D. J. Med. Chem. 2001, 44, 4577–4583; (c)
Xue, M.; Long, B. H.; Fairchild, C.; Johnston, K.; Rose,
W. C.; Kadow, J. F.; Vyas, D. M.; Chen, S.-H. Bioorg.
Med. Chem. Lett. 2000, 10, 1327–1331; (d) Ishiyama, T.;
Iimura, S.; Ohsuki, S.; Uoto, K.; Terasawa, H.; Soga, T.
Bioorg. Med. Chem. Lett. 2002, 12, 1083–1086.
6. Zhou, W.-S.; Lu, Z.-H.; Wang, Z.-M. Tetrahedron Lett.
1991, 32, 1467–1470.
NHBoc
O
H
O
H
a
b
O
HO
N
EtO
N
97%
80%
MOMO
Boc
Boc
OMOM
31
OMOM
32
15
OH
H
OH
H
d
c
e
EtO
N
N
97%
80%
89%
Boc
Boc
OMOM
OMOM
34
33
OH
OH
OH
HO
OH
H
H
HO
OH
H
H
Ph
f
H
H
HO
H
N
96%
OH
N
N
H
OH
Boc
H
7. (a) Bushey, M. L.; Haukaas, M. H.; OꢀDoherty, G. A. J.
Org. Chem. 1999, 64, 2984–2985; (b) Zhang, H.-X.; Xia,
P.; Zhou, W.-S. Tetrahedron: Asymmetry 2000, 11, 3439–
3447.
H
OMOM
OH
H
HCl
NOEs
35
36
Scheme 5. Reagents and conditions: (a) m-CPBA, CH2Cl2; (b)
HC(OEt)3, BF3ÆEt2O, 4 A MS, THF, 0 °C; (c) NaBH4, CeCl3Æ7H2O,
˚
8. Altenbach, H.-J.; Wischnat, R. Tetrahedron Lett. 1995, 36,
4983–4984.
MeOH, ꢁ78 °C; (d) NaBH4, HCO2H, 0 °C; (e) OsO4(cat.), NMO,
acetone/H2O 9:1 (v/v), rt; (f) 3 N HCl/CH3OH.
¨
9. Demir, A. S.; Sesenoglu, O.; Aksoy-Cam, H.; Kaya, H.;
Aydogan, K. Tetrahedron: Asymmetry 2003, 14, 1335–
1340.
10. (a) Koulocheri, S. D.; Haroutounian, S. A. Synthesis.
1999, 11, 1889–1892; (b) Battaglia, A.; Barbaro, G.;
Giorgianni, P.; Guerrini, A.; Pepe, A. Tetrahedron:
Asymmetry 2001, 12, 1015–1023.
11. (a) Ager, D. J.; Prakash, I.; Schaad, D. R. Chem. Rev.
1996, 96, 835–875; (b) Bergmeier, S. C. Tetrahedron 2000,
56, 2561–2576.
3,4,5-trihydroxypiperidine derivative 36, which is struc-
turally similar to 1-deoxygalactonojirimycin (a strong
inhibitor of a-glycosidase A in preclinical trials as poten-
tial therapy for Farbyꢀs Disease16b) and deoxygulonojiri-
mycin (DGJ, fucosidase inhibitor29a). The absolute
configuration of piperidine 36 was unambiguously con-
firmed by NOESY experiments.30
12. Prakash, G. K. S.; Mandal, M.; Schweizer, S.; Petasis, N.
A.; Olah, G. A. J. Org. Chem. 2002, 67, 3718–3723.
13. (a) Kobayashi, S.; Ishitani, H.; Ueno, M. J. Am. Chem.
Soc. 1998, 120, 431–432; (b) Matsunaga, S.; Kumagai, N.;
Harada, S.; Shibasaki, M. J. Am. Chem. Soc. 2003, 125,
4712–4713.
14. Marshall, J. A.; Gill, K.; Seletsky, B. M. Angew. Chem.,
Int. Ed. 2000, 39, 953–956.
15. Adrian, J. C., Jr.; Barkin, J. L.; Fox, R. J.; Chick, J. E.;
Hunter, A. D.; Nicklow, R. A. J. Org. Chem. 2000, 65,
6264–6267.
In conclusion, disclosed herein is a new and effective ac-
cess to the enantiomerically pure 2-amino-2-(furan-2-
yl)ethan-1-ols and derivatives using L- or D-serine as
common starting materials. Zinc-mediated propargyla-
tion of aldehydes, oxidative isomerization of homoprop-
argyl alcohols, and Ag(I)-catalyzed cycloisomerization
of a-allenylketones served as key steps. Advantages
of this approach include inexpensive materials and
reagents, ease of operation, excellent overall yields,

X. Cong et al. / Tetrahedron Letters 46 (2005) 8567–8571
8571
16. (a) Cong, X.; Liao, Q.-J.; Yao, Z.-J. J. Org. Chem. 2004,
69, 5314–5321; (b) Takahata, H.; Banba, Y.; Ouchi, H.;
Nemoto, H. Org. Lett. 2003, 5, 2527–2529; (c) Lillelund,
V. H.; Jensen, H. H.; Liang, X.; Bols, M. Chem. Rev. 2002,
102, 515–553.
28. (a) Koulocheri, S. D.; Magiatis, P.; Haroutounian, S. A. J.
Org. Chem. 2001, 66, 7915–7918; (b) Koulocheri, S. D.;
Haroutounian, S. A. Synthesis 1999, 11, 1889–1892.
29. (a) Haukaas, M. H.; OꢀDoherty, G. A. Org. Lett. 2001, 3,
401–404; (b) Koulocheri, S. D.; Pitsinos, E. N.; Harou-
tounian, S. A. Synthesis 2002, 12, 1707–1710; (c) Koulo-
cheri, S. D.; Magiatis, P.; Skaltsounis, A.-L.;
Haroutounian, S. A. Tetrahedron 2002, 58, 6665–6671.
17. Subramanian, T.; Lin, C. C.; Lin, C. C. Tetrahedron Lett.
2001, 42, 4079–4082.
18. (a) Marshall, J. A.; Bartley, G. S. J. Org. Chem. 1994, 59,
7169–7171; (b) Hashmi, A. S. K.; Schwarz, L.; Choi, J. H.;
Frost, T. M. Angew. Chem., Int. Ed. 2000, 39, 2285–2288;
(c) Hashmi, A. S. K.; Schwarz, L.; Bats, J. W. J. Prakt.
Chem. 2000, 342, 40–51.
19. (a) Liu, K.-G.; Yan, S.; Wu, Y.-L.; Yao, Z.-J. J. Org.
Chem. 2002, 67, 6758–6763; (b) Li, L.-S.; Wu, Y.-L.
Tetrahedron 2002, 58, 9049–9054.
20. Mengel, A.; Reiser, O. Chem. Rev. 1999, 99, 1191–
1223.
21. (a) Mckillop, A.; Taylor, R. J. K.; Waston, R. J.; Lewis,
N. Synthesis 1994, 31–33; (b) Dondoni, A.; Perrone, P.
Synthesis 1997, 527–529; (c) Garner, P.; Park, J. M. J.
Org. Chem. 1987, 52, 2361–2364.
19
30. Data for the key target compounds: 23: ½aꢀD 21.3 (c 1.5,
CH3OH). IR (KBr): 3327, 2945, 2836, 1606, 1505, 1152,
1023 cmꢁ1. 1H NMR (300 MHz, CD3OD): d 4.40–4.41 (m,
1H), 4.46–4.49 (m, 1H), 5.16 (d, J = 10.2 Hz, 1H), 5.33 (d,
J = 17.1 Hz, 1H), 5.63–5.74 (m, 1H), 6.36–6.37 (m, 1H),
6.48–6.49 (m, 1H), 7.47 (s, 1H) ppm. 13C NMR (125 MHz,
CD3OD): d 54.5, 73.0, 111.8, 112.1, 119.3, 136.8, 144.9,
148.6 ppm. ESIMS (m/z, %): 137.2 (MꢁNH2+, 75%),
154.2 (M+H+, 100%). HRMS (MALDI) calcd for
C8H11NO2Na (M+Na+): 176.0687; Found: 176.0683. 30:
19
½aꢀD ꢁ4.5 (c 1.4, CH3OH). IR (KBr): 3339, 2957, 2932,
1
2873, 2622, 1604, 1519, 1496, 1158, 1012 cmꢁ1. H NMR
(300 MHz, CD3OD): d 0.89 (t, J = 6.6 Hz, 3H), 1.29–
1.46 (m, 6H), 3.96–3.98 (m, 1H), 4.45 (br s, 1H), 6.48
(s, 1H), 6.59 (d, J = 2.7 Hz, 1H), 7.58 (s, 1H) ppm. 13C
NMR (75 MHz, CDCl3): d 14.5, 23.8, 29.1, 34.3, 54.7,
71.8, 111.8, 112.1, 144.9, 148.9 ppm. ESIMS (m/z, %):
167.3 (MꢁNH2+, 100%), 184.2 (M+H+, 40%). HRMS
(ESI) calcd for C10H18NO2 (M+H+): 184.1338; Found:
22. Bonini, C.; Righi, G. Tetrahedron 2002, 58, 4981–
5021.
23. (a) Lupattelli, P.; Bonini, C.; Caruso, L.; Gambacorta, A.
J. Org. Chem. 2003, 68, 3360–3362; (b) Hegedus, L. S. Acc.
Chem. Res. 1995, 28, 299–305.
24. (a) Williams, L.; Zhang, Z.-D.; Shao, F.; Carroll, P. J.;
27
´
Joullie, M. M. Tetrahedron 1996, 52, 11673–11694; (b)
184.1328. 36: ½aꢀD ꢁ22.7 (c 0.7, CH3OH). IR (KBr): 3384,
1
Nishida, A.; Sorimachi, H.; Iwaida, M.; Matsumizu, M.;
Kawate, T.; Nakagawa, M. Synlett 1998, 389–390.
25. Cong, X.; Hu, F.; Liu, K.-G.; Liao, Q.-J.; Yao, Z.-J. J.
Org. Chem. 2005, 70, 4514–4516.
26. (a) Coleman, R. S.; Carpenter, A. J. Tetrahedron Lett.
1992, 33, 1697–1700; (b) Ibuka, T.; Habashita, H.; Otaka,
A.; Fujii, N. J. Org. Chem. 1991, 56, 4370–4382.
27. Radunz, H.-E.; Devant, R. M.; Eiermann, V. Liebigs Ann.
Chem. 1988, 1103–1105.
2950, 2839, 1638, 1456, 1205, 1021, 703 cmꢁ1. H NMR
(500 MHz, CD3OD): d 3.06 (br s, 1H), 3.09 (br s, 1H), 3.55
(dd, J = 6.3, 1.5 Hz, 1H), 3.87 (dd, J = 4.2, 3.0Hz, 1H),
4.06–4.07 (m, 1H), 4.16–4.23 (m, 1H), 5.06 (d, J = 6.3 Hz,
1H), 7.34–7.52 (m, 5H) ppm. 13C NMR (125 MHz,
CDCl3): d 45.1, 59.0, 63.9, 68.8, 70.4, 73.2, 127.8, 130.0
(2C), 130.3 (2C), 141.3 ppm. ESIMS (m/z, %): 240.1
(M+Na+, 100%). HRMS (MALDI) calcd for C12H18NO4
(M+H+): 240.1236; Found: 240.1231.