An Efficient Synthesis of Aminocyclopentitols via the Stereoselective Amination of Polybenzyl Ethers Using Chlorosulfonyl Isocyanate

Article abstract of DOI:10.1055/s-2007-984518

An efficient stereoselective route for the preparation of stereoisomeric aminocyclopentitols 3-5 was achieved using a six-step sequence starting from the corresponding D-sugars. Key steps of the synthesis of the title compounds involved the regioselective

Full text of DOI:10.1055/s-2007-984518

LETTER
1711
An Efficient Synthesis of Aminocyclopentitols via the Stereoselective
Amination of Polybenzyl Ethers Using Chlorosulfonyl Isocyanate
E
fficient
n
S
ynthesis of
A
min
S
ocyclopentito
u
College of Pharmacy, Sungkyunkwan University, Suwon 440-746, Korea
Fax +82(31)2907773; E-mail: yhjung@skku.ac.kr
Received 4 April 2007
amine group into various allylic ethers using CSI9 and
demonstrated the application of this methodology to the
total synthesis of polyhydroxylated alkaloids.10 As a part
of our ongoing investigation of iminosugars, we con-
Abstract: An efficient stereoselective route for the preparation of
stereoisomeric aminocyclopentitols 3–5 was achieved using a six-
step sequence starting from the corresponding D-sugars. Key steps
of the synthesis of the title compounds involved the regioselective
and diastereoselective amination of cinnamylic 1,2-anti- or 1,2-syn- sidered preparing aminocyclopentitol precursors with a
tribenzyl ethers using chlorosulfonyl isocyanate (CSI), intramolec-
3-amino-1,2-diol functional group assembly.
ular olefin metathesis, and diastereoselective dihydroxylation.
We report herein a convenient synthetic route for the
Key words: aminocyclopentitol, chlorosulfonyl isocyanate, amina-
preparation of stereoisomeric 5-amino-1,2,3,4-cyclopen-
tion, mannostatin, dihydroxylation
tanetetrols 3–5 via the regioselective and stereoselective
amination of polybenzyl ethers using CSI (Figure 2). In
addition, we describe interesting results for the diastereo-
Glycosidases are involved in a wide range of important
selective dihydroxylation of olefin in polyfunctionalized
biological processes, such as intestinal digestion, the post-
carbocycles 10a–c.
translational processing of glycoproteins, and the lyso-
somal catabolism of glycoconjugates.1 Inhibitors of these
HO
OH
HO
OH
HO
OH
enzymes have received much attention and are currently
being used for treating diabetes,2 viral infections (e.g.,
HIV and influenza),3 malaria,4 and cancer.5 The majority
of these inhibitors are iminosugars, in which an oxygen
atom in a monosaccharide is replaced by a nitrogen atom,
and they have been often found in natural plants and
microorganisms. While these iminosugars and their deriv-
atives have been extensively studied, the development of
aminocyclopentitol analogues as glycosidase inhibitors
has received little attention.
HO
OH
HO
OH
HO
OH
NH2
NH2
NH2
4
5
3
Figure 2 Structure of various aminocyclopentitols
In initial studies, we investigated the regioselectivity and
diastereoselectivity of the reactions of stereoisomeric
tribenzyl ethers 6a–c with CSI, which were prepared from
commercially available D-sugars (D-lyxose, D-ribose and
D-arabinose), to provide the corresponding products 7a–c
(Table 1).
The aminocyclopentitols have been found in a number of
natural products, e.g. mannostatin A (1)6 and trehazoline
(2).7 In particular, mannostatin A (1), isolated from the
soil microorganism Streptoverticillus is the most potent
and specific class II a-mannosidase inhibitor reported to
date,8 which stimulated us to develop an efficient synthet-
ic route for the manufacture of various aminocyclopenti-
tol analogues as new a-mannosidase inhibitors (Figure 1).
As shown in entries 1 and 2, treatment of 1,2-anti-triben-
zyl ethers 6a and 6b with CSI in toluene at 0 °C furnished
the corresponding 1,2-anti-amino alcohols 7a and 7b with
excellent diastereoselectivities of 24:1 and 18:1, respec-
tively, in favor of the 1,2-anti-isomer. However, the reac-
tion of 1,2-syn-tribenzyl ethers 6c with CSI afforded the
desired 1,2-syn-amino alcohol 7c as a major product with
moderate diastereoselectivity of 1:5 in a 72% combined
yield (entry 3). Table 1 shows that the stereochemistries
of major products 7a–c were identical to those of the
corresponding substrates 6a–c. These results can be inter-
preted by the neighboring group effect leading to the
retention of the original configuration via a double config-
uration inversion.10,11
Recently, we described a new method for the regioselec-
tive and diastereoselective introduction of an N-protected
HO
HO
OH
HO
N
HO
NHR
HO
SMe
NH2
HO
2 (R = α-Glc)
1
The carbocycles 10a–c were straightforwardly pre-
pared in high overall yields (27–33%) from the benzyl-
protected lactols 8a–c using a five-step sequence, as
shown in Scheme 1. The Wittig olefination of 8a–c using
the DMSO anion12 and benzyltriphenylphosphonium
Figure 1 Mannostatin A (1) and trehazoline (2)
SYNLETT 2007, No. 11, pp 1711–1714
0
3
.0
7
.2
0
0
7
Advanced online publication: 25.06.2007
DOI: 10.1055/s-2007-984518; Art ID: U02907ST
© Georg Thieme Verlag Stuttgart · New York

1712
I. S. Kim et al.
LETTER
Table 1 Diastereoselective CSI Reactions of Various Cinnamylic Polybenzyl Ethers 7a–c
Entry
1
Substrate
Product
Yield (%)a
74
Ratio (anti/syn)b
24:1
18:1
1:5
OBn
OBn
OBn OBn
OBn NHCbz
6a
7a
7b
7c
2
3
80
72
OBn
OBn
OBn OBn
OBn NHCbz
6b
6c
OBn
OBn
OBn OBn
OBn NHCbz
a Isolated yield of pure materials.
b Isomeric ratio as determined by 1H NMR analysis.
OBn
chloride in THF at 45 °C afforded the alcohols 9a–c in
high yields. Oxidation of the alcohols 9a–c with Dess–
Martin reagent yielded the corresponding aldehydes,
which were then subjected to the Wittig reaction using
NaHMDS and methyltriphenylphosphonium bromide, to
furnish the dienic compounds 6a–c. Reactions between
the polybenzyl ethers 6a–c and CSI were carried out in
toluene at 0 °C. These were followed by desulfonylation
using aqueous 25% sodium sulfite solution, to furnish the
cinnamylic amine products 7a–c with high diastereoselec-
tivity.13 Finally, treatment of 7a–c with second-generation
Grubbs’ catalyst [(IMesH2)(PCy3)(Cl)2Ru=CHPh]14 in
toluene at 80 °C provided the carbocyclic compounds
10a–c in good yields.15
OBn
a
3
4
BnO
OBn
OH
4
3
HO
OBn OBn
O
(3R,4R)-9a 94%
(3S,4S)-9b 80%
(3R,4S)-9c 95%
(3S,4S)-8a
(3R,4R)-8b
(3S,4R)-8c
OBn
3
4
c
b
OBn OBn
(3R,4S)-6a 57%
(3S,4R)-6b 56%
(3R,4R)-6c 58%
BnO
Next, we investigated the dihydroxylation of the stereo-
isomeric cyclic allylic amines 10a–c using a catalytic
amount of OsO4 in 80% acetone (Scheme 2).16 Ratios of
stereoisomers were determined by HPLC analysis of the
inseparable reaction mixture, and the relative configura-
tions of 11a–13a and 11b were assigned by NOE studies
of the isolated pure materials obtained by additional puri-
fication processes, involving introduction and removal of
the acetonide group.17 In all cases, dihydroxylation oc-
curred preferentially from the anti-direction with respect
to the allylic benzyloxy group at C-4 to give 11a–13a as
major products, although the level of diastereoselectivity
depended upon the ring substitution pattern. Interestingly,
osmylation of 10b with its bottom face completely shield-
ed by three substituents did not produce a higher level of
diastereoselectivity than that observed for 10c. The excel-
lent diastereoselectivity (21:1) of 10c could be explained
by steric interaction between the bulky benzyloxy groups
at C-4/C-5 and the oxidant (OsO4), the directing ability of
the NHCO group18 (as reasonably good hydrogen donor),
and allylic strain19 in the five-membered ring system. Fi-
nally, hydrogenolysis of the diols 11a–13a and 11b with
OBn
3
4
d
4
3
BnO
OBn NHCbz
NHCbz
(3R,4R)-7a 74%
(3S,4S)-7b 80%
(3R,4S)-7c 72%
(3R,4R)-10a 84%
(3S,4S)-10b 75%
(3R,4S)-10c 76%
Scheme 1 Reagents and conditions: (a) NaH, DMSO, BnPPh3Cl,
THF, 45 °C; (b) (i) Dess–Martin periodinane, CH2Cl2, 0 °C; (ii) NaH-
MDS, MePPh3Br, THF, 0 °C; (c) (i) CSI, Na2CO3, toluene, 0 °C; (ii)
25% Na2SO3, r.t.; (d) (IMesH2)(PCy3)(Cl)2Ru=CHPh (5 mol%), to-
luene, 80 °C.
10% Pd/C and 6 N HCl in methanol followed by purifi-
cation using ion-exchange resin provided the free amines
3–5 as viscous liquids.20
In conclusion, an efficient stereoselective route for the
preparation of stereoisomeric aminocyclopentitols 3–5
was accomplished from the readily available D-sugars via
the regio- and diastereoselective amination of polybenzyl
ethers using chlorosulfonyl isocyanate, intramolecular
olefin metathesis leading to carbocyclic ring skeleton
Synlett 2007, No. 11, 1711–1714 © Thieme Stuttgart · New York

LETTER
Efficient Synthesis of Aminocyclopentitols
1713
(5) (a) Nishimura, Y. Curr. Top. Med. Chem. 2003, 3, 575.
(b) Ostrander, G. K.; Scribner, N. K.; Rohrschneider, L. R.
Cancer Res. 1988, 48, 1091. (c) Tsuruoka, T.; Fukuyasu,
H.; Ishii, M.; Usui, T.; Shibahara, S.; Inouye, S. J. Antibiot.
1996, 49, 155.
BnO
BnO
BnO
OH
BnO
OH
a
+
BnO
OH
BnO
OH
80%
NHCbz
NHCbz
NHCbz
(6) For a recent review of synthetic and biological features of
the mannostatins, see: Berecibar, A.; Grandjean, C.;
Siriwardena, A. Chem. Rev. 1999, 99, 779.
10a
11a
11b
11a/11b = 2.6:1
3 (88%)
(7) (a) Ando, O.; Nakajima, M.; Hamano, K.; Itoi, K.;
Takahashi, S.; Takamatsu, Y.; Sato, A.; Enokita, R.;
Haruyama, H. J. Antibiot. 1993, 46, 1116. (b) Ando, O.;
Satake, H.; Itoi, K.; Sato, A.; Nakajima, M.; Takahashi, S.;
Haruyama, H. J. Antibiot. 1991, 44, 1165.
b
+
4 (83%)
BnO
BnO
OH
(8) Aoyagi, T.; Yamamoto, T.; Kojiri, K.; Morishima, H.;
Nagai, M.; Hamada, M.; Takeuchi, T.; Umezawa, H.
J. Antibiot. 1989, 42, 883.
a
b
5
BnO
BnO
OH
NHCbz
95%
87%
(9) (a) Kim, J. D.; Kim, I. S.; Hua, J. C.; Zee, O. P.; Jung, Y. H.
Tetrahedron Lett. 2005, 46, 1079. (b) Jung, Y. H.; Kim, J.
D. Arch. Pharm. Res. 2005, 28, 382. (c) Kim, J. D.; Zee, O.
P.; Jung, Y. H. J. Org. Chem. 2003, 68, 3721. (d) Kim, J.
D.; Han, G.; Zee, O. P.; Jung, Y. H. Tetrahedron Lett. 2003,
44, 733. (e) Jung, Y. H.; Kim, J. D. Arch. Pharm. Res. 2003,
26, 667. (f) Kim, J. D.; Han, G.; Jeong, L. S.; Park, H.-J.;
Zee, O. P.; Jung, Y. H. Tetrahedron 2002, 58, 4395.
(g) Kim, J. D.; Lee, M. H.; Han, G.; Park, H.; Zee, O. P.;
Jung, Y. H. Tetrahedron 2001, 57, 8257. (h) Jung, Y. H.;
Kim, J. D. Arch. Pharm. Res. 2001, 24, 371. (i) Kim, J. D.;
Lee, M. H.; Lee, M. J.; Jung, Y. H. Tetrahedron Lett. 2000,
41, 5073. (j) Jung, Y. H.; Kim, J. D. Arch. Pharm. Res. 2000,
23, 574.
(10) (a) Kim, I. S.; Oh, J. S.; Zee, O. P.; Jung, Y. H. Tetrahedron
2007, 63, 2622. (b) Kim, I. S.; Ji, Y. J.; Jung, Y. H.
Tetrahedron Lett. 2006, 47, 7289. (c) Kim, I. S.; Zee, O. P.;
Jung, Y. H. Org. Lett. 2006, 8, 4101. (d) Kim, I. S.; Kim, J.
D.; Ryu, C. B.; Zee, O. P.; Jung, Y. H. Tetrahedron 2006, 62,
9349. (e) Kim, J. D.; Kim, I. S.; Jin, C. H.; Zee, O. P.; Jung,
Y. H. Org. Lett. 2005, 7, 4025.
(11) (a) Krow, G. R.; Yuan, J.; Lin, G.; Sonnet, P. E. Org. Lett.
2002, 4, 1259. (b) Roberts, D. D. J. Org. Chem. 1997, 62,
1857. (c) Winstein, S.; Allred, E.; Heck, R.; Grick, R.
Tetrahedron 1958, 3, 1.
(12) (a) For a recent review of Wittig olefination, see:
Maryanoff, B. E.; Reitz, A. B. Chem. Rev. 1989, 89, 863.
(b) Choi, W. J.; Park, J. K.; Yoo, S. J.; Kim, H. O.; Moon, H.
R.; Chun, M. W.; Jung, Y. H.; Jeong, L. S. J. Org. Chem.
2001, 66, 6490.
NHCbz
12a selectivity = 17:1
10b
BnO
BnO
OH
a
b
5
BnO
BnO
OH
86%
92%
NHCbz
NHCbz
10c
13a selectivity = 21:1
Scheme 2 Reagents and conditions: (a) cat. OsO4, 50% NMO, 80%
acetone, r.t.; (b) (i) 2,2-dimethoxypropane, PPTS, CH2Cl2, r.t.; (ii) se-
paration; (iii) p-TsOH, MeOH, 40 °C; (iv) 10% Pd/C, H2, 6 N HCl,
MeOH, r.t.; (v) DOWEX-50WX8 (H+ form, 0.5 M NH4OH as eluent).
formation, and diastereoselective dihydroxylation. More-
over, we have provided useful information for the dihy-
droxylation of olefins in 1-amino-4,5-diol cyclopentenes.
Currently, we are preparing other aminocyclitols and ami-
nocyclopentitols for evaluation as potent a-mannosidase
inhibitors.
Acknowledgment
This research was supported by the Seoul Research and Business
Development (Seoul R&BD) Program (#10541), and by the Brain
Korea 21 (BK21) Program.
(13) Characterization data for 7a–c:
7a: (Z:E = 2.5:1, anti:syn = 24:1); [a]D30 –14.9 (c = 1.0,
CHCl3). 1H NMR (500 MHz, CDCl3): d = 3.50–3.53 (t, J =
4.5 Hz, 0.71 H), 3.60–3.61 (br, 0.29 H), 3.91–4.01 (m, 1 H),
4.32 (d, J = 11.5 Hz, 0.29 H), 4.33 (d, J = 12.0 Hz, 0.71 H),
4.60–4.77 (m, 3.29 H), 5.01–5.15 (m, 4.13 H), 5.29 (d, J =
17.0 Hz, 0.29 H), 5.38 (d, J = 10.0 Hz, 0.29 H), 5.53 (t, J =
10.0, 12.0 Hz, 0.71 H), 5.70–5.84 (m, 1.71 H), 5.90–5.99 (m,
0.29 H),6.00 (dd, J = 7.5, 15.5 Hz, 0.29 H), 6.52 (d, J = 15.5
Hz, 0.29 H), 6.53 (d, J = 15.5 Hz, 0.71 H), 7.23–7.36 (m, 20
H). 13C NMR (125 MHz, CDCl3): d = 49.69, 66.67, 70.64,
73.65, 81.66, 81.94, 119.76, 120.06, 126.80, 127.51, 127.94,
127.99, 128.09, 128.17, 128.40, 128.55, 128.66, 128.69,
132.55, 132.85, 134.88, 135.12, 136.58, 137.05, 138.14,
138.33, 155.99. HRMS (FAB): m/z [M + H+] calcd for
C35H36NO4: 534.2644; found: 534.2639.
References and Notes
(1) (a) Asano, N. Curr. Top. Med. Chem. 2003, 3, 471.
(b) Elbein, A. D. FASEB J. 1991, 5, 3055. (c) Asano, N.;
Nash, R. J.; Molyneux, R. J.; Fleet, G. W. J. Tetrahedron:
Asymmetry 2000, 11, 1645.
(2) (a) Somsak, L.; Nagya, V.; Hadady, Z.; Docsa, T.; Gergely,
P. Curr. Pharm. Des. 2003, 9, 1177. (b) Johnson, P. S.;
Lebovitz, H. E.; Coniff, R. F.; Simonson, D. C.; Raskin, P.;
Munera, C. L. J. Clin. Endocrinol. Metab. 1998, 83, 1515.
(3) (a) Greimel, P.; Spreitz, J.; Stutz, A. E.; Wrodnigg, T. M.
Curr. Top. Med. Chem. 2003, 3, 513. (b) Fleet, G. W. J.;
Karpas, A.; Dwek, R. A.; Fellows, L. E.; Tyms, A. S.;
Peturrson, S.; Namgoong, S. K.; Ramsden, N. G.; Smith, P.
W.; Son, J. C.; Wilson, F.; Witty, D. R.; Jacob, G. S.;
Rademacher, T. W. FEBS Lett. 1988, 237, 128. (c) Gruters,
R. A.; Neefjes, J. J.; Tersmette, M.; de Goede, R. E. Y.; Tulp,
A.; Huisman, H. G.; Miedema, F.; Ploegh, H. L. Nature
(London) 1987, 330, 74.
7b: (Z:E = 2.6:1, anti:syn = 18:1); [a]D25 –79.6 (c = 0.1,
CHCl3). 1H NMR (500 MHz, CDCl3): d = 3.68–3.73 (br,
0.56 H), 3.80 (t, J = 7.0 Hz, 0.72 H), 3.88–3.92 (m, 0.72 H),
4.29 (d, J = 11.5 Hz, 0.28 H), 3.39 (d, J = 11.5 Hz, 0.72 H),
4.47 (d, J = 11.5 Hz, 0.28 H), 4.54 (d, J = 11.5 Hz, 0.72 H),
(4) Bitonti, A. J.; Sjoersma, A.; McCann, P. P. Eur. Patent Appl.
EP423728, 1991.
Synlett 2007, No. 11, 1711–1714 © Thieme Stuttgart · New York

1714
I. S. Kim et al.
LETTER
4.57 (d, J = 11.5 Hz, 0.28 H), 4.61 (d, J = 11.5 Hz, 0.72 H),
4.63 (d, J = 11.5 Hz, 0.28 H), 4.67 (d, J = 11.5 Hz, 0.72 H),
4.89 (br, 0.28 H), 5.06–5.16 (m, 2 H), 5.25 (t, J = 8.0 Hz,
0.72 H), 5.35–5.44 (m, 3 H), 5.76 (dd, J = 10.0, 10.5 Hz, 0.72
H), 5.85–5.94 (m, 1 H), 6.17 (dd, J = 8.0, 15.5 Hz, 0.28 H),
6.49 (d, J = 15.5 Hz, 0.28 H), 6.63 (d, J = 10.5 Hz, 0.72 H),
7.03–7.46 (m, 20 H). 13C NMR (125 MHz, CDCl3): d =
50.32, 66.87, 70.47, 70.53, 74.49, 81.12, 81.34, 83.20,
83.50, 119.70, 120.25, 126.78, 127.53, 127.60, 127.85,
128.01, 128.15, 128.23, 128.37, 128.58, 128.65, 128.68,
128.76, 128.90, 132.74, 132.82, 136.18, 136.58, 138.25,
155.60. HRMS (FAB): m/z [M + H+] calcd for C35H36NO4:
534.2644; found: 534.2640.
(17) Characterization data for 11a–13a and 11b:
11a: [a]D23 +1.0 (c = 0.22, CHCl3). 1H NMR (500 MHz,
CDCl3): d = 3.92–4.25 (m, 5 H), 4.46 (d, J = 11.0 Hz, 1 H),
4.53 (d, J = 12.0 Hz, 1 H), 4.57 (d, J = 11.0 Hz, 1 H), 4.65
(d, J = 12.0 Hz, 1 H), 5.11 (d, J = 12.5 Hz, 1 H), 5.16 (d, J =
12.5 Hz, 1 H), 5.54–5.59 (br, 1 H), 7.22–7.36 (m, 15 H). 13
NMR (125 MHz, CDCl3): d = 53.83, 67.33, 72.06, 72.71,
73.41, 80.22, 82.63, 88.40, 128.04, 128.09, 128.24, 128.39,
128.45, 128.71, 128.78, 128.81, 136.52, 137.20, 137.92,
154.56. HRMS (FAB): m/z [M + H+] calcd for C27H30NO6:
464.2073; found: 464.2068.
C
11b: [a]D22 –18.2 (c = 0.08, CHCl3). 1H NMR (500 MHz,
CDCl3): d = 1.58–1.64 (br, 1 H), 2.84–2.88 (br, 1 H), 3.86
(dd, J = 4.0, 4.5 Hz, 1 H), 3.93 (t, J = 6.5 Hz, 1 H), 4.01–4.21
(m, 3 H), 4.78 (d, J = 11.5 Hz, 1 H), 4.52–4.60 (m, 2 H), 4.71
(d, J = 11.5 Hz, 1 H), 5.12 (s, 2 H), 5.52 (br s, 1 H), 7.24–
7.48 (m, 15 H). 13C NMR (125 MHz, CDCl3): d = 57.16,
67.41, 69.13, 72.46, 73.06, 77.49, 80.21, 82.78, 128.22,
128.28, 128.33, 128.42, 128.49, 128.79, 136.41, 137.42,
137.57, 157.66. HRMS (FAB): m/z [M + Na+] calcd for
C27H29NO6Na: 486.1893; found: 486.1896.
7c: (Z:E = 2.8:1, anti:syn = 1:5); [a]D25 +1.2 (c = 1.0, CHCl3).
1H NMR (500 MHz, CDCl3): d = 3.56 (t, J = 7.5 Hz, 0.74 H),
3.71 (dd, J = 3.5, 6.5 Hz, 0.26 H), 3.88–3.93 (m, 1 H), 4.30
(d, J = 11.5 Hz, 0.26 H), 4.45–4.64 (m, 3.46 H), 4.76 (d, J =
11.5 Hz, 0.26 H), 4.91–4.93 (br, 0.26 H), 5.09–5.14 (m, 2.74
H), 5.31–5.64 (m, 3 H), 5.84 (dd, J = 10.0, 11.0 Hz, 0.74 H),
5.84–5.87 (m, 1 H), 6.18 (dd, J = 8.0, 16.0 Hz, 0.26 H), 6.53
(d, J = 11.0 Hz, 0.74 H), 6.56 (d, J = 16.0 Hz, 0.26 H), 7.06–
7.49 (m, 20 H). 13C NMR (125 MHz, CDCl3): d = 54.78,
66.88, 70.52, 74.50, 74.66, 81.11, 83.47, 120.33, 126.06,
126.81, 127.82, 127.87, 127.97, 128.14, 128.17, 128.27,
128.35, 128.53, 128.67, 128.69, 128.72, 128.79, 132.76,
136.18, 136.86, 137.01, 138.30, 155.80. HRMS (FAB):
m/z [M + H+] calcd for C35H36NO4: 534.2644; found:
534.2654.
12a: [a]D23 +7.3 (c = 0.44, CHCl3). 1H NMR (500 MHz,
CDCl3): d = 1.82 (br s, 1 H), 3.09 (br s, 1 H), 3.91–3.99 (m,
3 H), 4.17 (dd, J = 4.5, 5.5 Hz, 1 H), 4.23 (br d, J = 3.0 Hz,
1 H), 4.52 (d, J = 12.0 Hz, 1 H), 4.68 (d, J = 12.0 Hz, 1 H),
4.76 (d, J = 12.0 Hz, 1 H), 4.79 (d, J = 12.0 Hz, 1 H), 5.14
(d, J = 12.5 Hz, 1 H), 5.10 (d, J = 12.5 Hz, 1 H), 5.62 (d, J =
6.0 Hz, 1 H), 7.27–7.40 (m, 15 H). 13C NMR (125 MHz,
CDCl3): d = 58.34, 67.35, 72.63, 73.27, 73.59, 76.42, 77.58,
84.59, 127.94, 128.01, 128.21, 128.37, 128.50, 128.69,
128.76, 128.82, 136.45, 138.04, 138.29, 157.59. HRMS
(FAB): m/z [M + H+] calcd for C27H30NO6: 464.2073; found:
464.2083.
(14) For recent reviews of ring-closing metathesis, see:
(a) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34,
18. (b) Fürstner, A. Angew. Chem. Int. Ed. 2000, 39, 3012.
(15) Characterization data for 10a–c:
10a: [a]D29 –32.9 (c = 1.0, CHCl3). 1H NMR (500 MHz,
CDCl3): d = 4.09 (br t, J = 5.5 Hz, 1 H), 4.52–4.61 (m, 5 H),
4.90–4.93 (br, 1 H), 5.12 (s, 2 H), 5.19 (d, J = 7.5 Hz, 1 H),
5.95 (d, J = 6.0 Hz, 1 H), 6.03 (d, J = 5.5 Hz, 1 H), 7.27–7.40
(m, 15 H). 13C NMR (125 MHz, CDCl3): d = 55.67, 66.99,
71.92, 72.79, 82.56, 86.81, 128.00, 128.09, 128.17, 128.22,
128.34, 128.61, 128.67, 128.72, 128.74, 132.89, 134.65,
136.76, 137.77, 138.37, 156.37. HRMS (FAB): m/z [M +
H+] calcd for C27H28NO4: 430.2018; found: 430.2020.
10b: [a]D25 –79.6 (c = 0.1, CHCl3). 1H NMR (500 MHz,
CDCl3): d = 4.02 (t, J = 5.5 Hz, 1 H), 4.30 (dd, J = 2.5, 5.0
Hz, 1 H), 4.64 (d, J = 12.0 Hz, 1 H), 4.65 (d, J = 12.0 Hz, 1
H), 4.69–4.71 (br, 1 H), 4.72 (d, J = 12.0 Hz, 1 H), 4.79 (d,
J = 12.0 Hz, 1 H), 5.12 (s, 2 H), 5.29 (d, J = 9.0 Hz, 1 H),
6.05 (dd, J = 2.0, 6.0 Hz, 1 H), 6.09 (dd, J = 3.0, 6.0 Hz, 1
H), 7.27–7.38 (m, 15 H). 13C NMR (125 MHz, CDCl3): d =
54.65, 66.88, 72.31, 72.58, 78.42, 80.03, 127.86, 127.90,
128.02, 128.05, 128.22, 128.61, 128.69, 133.06, 135.08,
136.90, 138.30, 138.79, 156.36. HRMS (FAB): m/z [M +
H+] calcd for C27H28NO4: 430.2018; found: 430.2013.
10c: [a]D29 +6.2 (c = 1.0, CHCl3). 1H NMR (500 MHz,
CDCl3): d = 4.02 (t, J = 5.5 Hz, 1 H), 4.30 (dd, J = 2.5, 5.0
Hz, 1 H), 4.64 (d, J = 12.0 Hz, 1 H), 4.65 (d, J = 12.0 Hz, 1
H), 4.70–4.73 (br m, 2 H), 4.79 (d, J = 12.0 Hz, 1 H), 5.12
(s, 2 H), 5.28 (d, J = 9.0 Hz, 1 H), 6.05 (dd, J = 1.5, 6.0 Hz,
1 H), 6.08 (dd, J = 2.5, 6.5 Hz, 1 H), 7.27–7.41 (m, 15 H).
13C NMR (125 MHz, CDCl3): d = 54.65, 66.87, 72.31, 72.58,
78.44, 80.03, 127.84, 127.90, 128.01, 128.03, 128.21,
128.60, 128.69, 133.05, 135.08, 136.91, 138.30, 143.67,
156.35. HRMS (FAB): m/z [M + H+] calcd for C27H28NO4:
430.2018; found: 430.2019.
13a: [a]D29 –2.5 (c = 1.0, CHCl3). 1H NMR (300 MHz,
CDCl3): d = 2.98–3.22 (br, 2 H), 3.90–3.98 (br m, 2 H),
4.21–4.26 (br m, 3 H), 4.51 (d, J = 11.7 Hz, 1 H), 4.71 (d,
J = 12.0 Hz, 1 H), 4.79 (d, J = 12.0 Hz, 1 H), 4.82 (d, J = 11.7
Hz, 1 H), 5.17 (s, 2 H), 5.63 (br d, J = 5.7 Hz, 1 H), 7.23–
7.65 (m, 15 H). 13C NMR (125 MHz, CDCl3): d = 58.41,
67.34, 72.66, 73.31, 73.61, 76.46, 77.52, 84.55, 127.91,
127.98, 128.17, 128.34, 128.47, 128.66, 128.74, 128.80,
136.44, 138.00, 138.29, 157.69. HRMS (FAB): m/z
[M + H+] calcd for C27H30NO6: 464.2073; found: 464.2072.
(18) Donohoe, T. J.; Blades, K.; Moore, P. R.; Waring, M. J.;
Winter, J. J. G.; Helliwell, M.; Newcombe, N. J.; Stemp, G.
J. Org. Chem. 2002, 67, 7946.
(19) Poli, G. Tetrahedron Lett. 1989, 30, 7385.
(20) Characterization data for 3–5:
3: [a]D23 +6.3 (c = 0.79, MeOH). 1H NMR (500 MHz, D2O):
d = 3.22 (t, J = 3.0 Hz, 1 H), 3.73 (dd, J = 4.0, 7.5 Hz, 1 H),
3.80 (dd, J = 3.0, 7.5 Hz, 1 H), 3.91–3.94 (m, 2 H). 13C NMR
(125 MHz, D2O): d = 51.91, 73.32, 75.91, 76.01, 83.35.
HRMS (FAB): m/z [M + H+] calcd for C5H12NO4: 150.0766;
found: 150.0766.
4: [a]D23 –11.9 (c = 0.23, MeOH). 1H NMR (500 MHz, D2O):
d = 3.35 (t, J = 8.0 Hz, 1 H), 3.86–3.92 (m, 2 H), 3.99 (t, J =
4.5 Hz, 1 H), 4.07 (dd, J = 6.0, 8.0 Hz, 1 H). 13C NMR (125
MHz, D2O): d = 56.37, 71.18, 73.37, 74.80, 76.84. HRMS
(FAB): m/z [M + H+] calcd for C5H12NO4: 150.0766; found:
150.0767.
5: [a]D22 –2.3 (c = 1.0, MeOH). 1H NMR (500 MHz, D2O):
d = 3.46 (t, J = 6.0 Hz, 1 H), 3.96 (t, J = 5.0 Hz, 1 H), 4.00
(dd, J = 6.0, 6.5 Hz, 1 H), 4.19 (t, J = 7.0 Hz, 1 H), 4.22 (dd,
J = 4.5, 5.5 Hz, 1 H). 13C NMR (125 MHz, D2O): d = 57.19,
67.83, 71.83, 73.85, 76.39. HRMS (FAB): m/z [M + H+]
calcd for C5H12NO4: 150.0766; found: 150.0767.
(16) (a) Cha, J. K.; Christ, W. J.; Kishi, Y. Tetrahedron Lett.
1983, 24, 3947. (b) Cha, J. K.; Christ, W. J.; Kishi, Y.
Tetrahedron Lett. 1983, 24, 3943. (c) VanRheenen, V.;
Kelly, R. C.; Cha, D. Y. Tetrahedron Lett. 1976, 17, 1973.
Synlett 2007, No. 11, 1711–1714 © Thieme Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not
be copied or emailed to multiple sites or posted to a listserv without the copyright holder's
express written permission. However, users may print, download, or email articles for
individual use.