Application of a samarium(II)-mediated spirocyclisation in an asymmetric approach to the cyclopentanol motif of stolonidiol

Article abstract of DOI:10.1055/s-2007-1000821

An asymmetric approach to the cyclopentanol motif of the biologically active, marine natural product stolonidiol has been developed. The approach involves the asymmetric synthesis of chiral γ,δ-unsaturated ketones and their spirocyclisation using SmI₂. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-1000821

LETTER
3155
Application of a Samarium(II)-Mediated Spirocyclisation in an Asymmetric
Approach to the Cyclopentanol Motif of Stolonidiol
S
m(II)-Mediate
i
d
Spiro
s
c
yclisatio
a
n
A. Sloan,a Thomas M. Baker,a Simon J. F. Macdonald,b David J. Procter*a
a
The School of Chemistry, University of Manchester, Oxford Road, Manchester, M13 9PL, UK
GlaxoSmithKline R&D Ltd, Medicines Research Centre, Gunnels Wood Road, Stevenage, SG1 2NY, UK
Fax +44(161)2754939; E-mail: david.j.procter@manchester.ac.uk
b
Received 21 August 2007
tivity against P388 leukemia cells in vitro (IC50 = 0.015 mg
mL–1), in addition to other significant biological activity.4
More recently, stolonidiol has been shown to display po-
tent choline acetyltransferase (ChAT) inducible activity
suggesting that it may act as a potent neurotrophic factor-
like agent on the cholinergic nervous system.5 Agents
with neurotrophic factor-like activity are potential thera-
peutics for dementia and disorders such as Alzheimer’s
disease. The pioneering work of Yamada led to the only
total synthesis of stolonidiol in 2001.6 We felt that the
considerable biological interest associated with the com-
pound necessitated the development of a shorter, more
flexible route to stolonidiol that would allow comprehen-
sive structure-activity relationship studies to be carried
out.5
Abstract: An asymmetric approach to the cyclopentanol motif of
the biologically active, marine natural product stolonidiol has been
developed. The approach involves the asymmetric synthesis of
chiral g,d-unsaturated ketones and their spirocyclisation using
SmI2.
Key words: samarium, radical reactions, asymmetric synthesis,
natural products, spiro compounds
Samarium(II) iodide (SmI2) is a one-electron reducing
agent that has found widespread use in organic synthesis.1
Cyclisation reactions are arguably the most useful trans-
formations mediated by SmI2 and these have been used
extensively in natural product synthesis.1f
We have previously studied the Sm(II)-mediated cyclisa-
tion reactions of g,d-unsaturated aldehydes2 and ketones.3
In particular, we have reported that a simple class of un-
saturated ketone can be directed down either of two dis-
tinct, stereoselective reaction pathways, depending upon
the alcohol co-solvent employed in the process.3b
OH
HO
O
4
stolonidiol
OH
5
OH
O
OR
BnO
O
Me
OH
Me OH
O
i
ii
Me
O
O
O
O
O
H
O
O
O
O
1
2
3
OH
Scheme 1 Reagents and conditions: (i) SmI2, THF–MeOH (4:1),
0 °C, 71%; (ii) SmI2, THF–t-BuOH (4:1), 0 °C, 64%.
BnO
BnO
OH
OR
7
6
OR
O
For example, lactone 1 underwent cyclisation upon treat-
ment with SmI2 in THF with MeOH as co-solvent to give
cyclopentanol 2. Using t-BuOH as co-solvent, under oth-
erwise identical conditions, gave cyclobutanol derivative
3 (Scheme 1). In this Letter we describe the application of
the former, spirocyclisation process in an asymmetric ap-
proach to the functionalised cyclopentanol motif found in
the natural product stolonidiol. Our work constitutes only
the second synthetic study on this important target.
Figure 1 Retrosynthetic analysis of stolonidiol
We believe that a suitably protected intermediate 5 is a
versatile intermediate en route to the natural product that
can accommodate several approaches to the 11-membered
ring of the target. The new, diastereoselective SmI2 cycli-
sation process, developed in our laboratory, allowed us to
consider an unusual disconnection in a retrosynthetic
study of 5. We envisaged that 5 could be obtained from
spirocyclic cyclopentanol 6 that in turn should be accessi-
ble using the SmI2-mediated sequential conjugate reduc-
The diterpenoid stolonidiol (4; Figure 1) was isolated in
1987 from a Japanese soft coral by Yamada.4 Initial as-
says showed the compound to display strong cytotoxic ac-
tion–intramolecular
aldol
cyclisation3b
of
enantiomerically pure ketone 7. We have previously
shown that the cyclisations of simpler substrates (e.g. 1)
give only syn spirocyclic products (e.g. 2).3b Similar syn
SYNLETT 2007, No. 20, pp 3155–3159
Advanced online publication: 03.12.2007
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x
.x
x
.2
0
0
7
DOI: 10.1055/s-2007-1000821; Art ID: D26107ST
© Georg Thieme Verlag Stuttgart · New York

3156
L. A. Sloan et al.
LETTER
selectivity is required for our planned approach to 5 enate (TPAP)]10 then gave 13 and 14. Finally,
(Figure 1).
dihydroxylation of the terminal olefin in 13 and 14, oxida-
tive cleavage and Wittig reaction with phosphorane 15
gave 16 and 17, respectively, as single double-bond iso-
mers by NMR (Scheme 2).
We began by developing an asymmetric route to cyclisa-
tion substrates 7, bearing methoxyethoxymethyl (MEM)
ether and methoxymethyl (MOM) ether groups (R =
MEM, R = MOM). Not only do these protecting groups We also chose to prepare cyclisation substrate 20 bearing
offer orthogonal protection in our synthetic approach but a free hydroxyl group that is also capable of influencing
they are also capable of coordination to Sm(III) and could the stereochemical course of the cyclisation through coor-
influence the diastereoselectivity of the cyclisation reac- dination to Sm(III). The synthesis of 20 required modifi-
tions. In developing an asymmetric route to ketones 7, we cation of the asymmetric route: deprotection of the
were aware that synthetic flexibility would be important secondary TBDMS ether in intermediate 12 and oxidation
for the preparation of alternative cyclisation substrates in using Ley’s reagent gave 18 (88% overall). One-pot dihy-
the future. Our approach to the requisite cyclisation sub- droxylation and oxidative cleavage11of the terminal olefin
strates is shown in Schemes 2 and 3.
then gave lactol 19 as a 1:1.4 mixture of diastereoisomers.
Treatment with phosphorane 15 gave 20 as a single ste-
reoisomer in moderate yield (Scheme 3).
O
O
O
O
OH
i
O
N
O
N
OBn
OBn
OBn
O
O
HO
8
10
O
i
ii
Bn
Bn
OBn
OBn
O
12
OBn
19
18
HO
9
ii
iii
OTBS
O
OTBS
HO
O
iii
HO
MeO
OBn
OBn
20
12
11
O
iv
O
Scheme 3 Reagents and conditions: (i) (a) TBAF, THF; (b) TPAP,
NMO, CH2Cl2, 88% for 2 steps; (ii) OsO4, NaIO4, 2,6-lutidine, dioxa-
ne, H2O, 99%; (iii) 15, THF, r.t., 64%.
O
O
RO
RO
v
OBn
We initially examined the cyclisation of substrates 16 and
17. We were pleased to find that treatment of 16 with SmI2
in THF–MeOH at 0 °C, our standard cyclisation condi-
tions,3b gave diastereoisomeric spirocycles 21a and 22a in
a 1:1 ratio (32%) although acyclic reduction product 23a
was the major product (62%, 1:1 mixture of diastereoiso-
mers) (Scheme 4). The MOM substrate 17 was found to
behave similarly, giving spirocycles 21b/22b in 35%
yield. The stereochemistry of 21a,b and 22a,b was as-
signed by X-ray crystallography and NOE studies (vide
infra).
O
O
13 R = MEM
14 R = MOM
Ph3P
O
O
16 R = MEM
17 R = MOM
15
Scheme 2 Reagents and conditions: (i) n-Bu2BOTf, i-Pr2EtN,
CH2Cl2, 9, –78 °C, 100% (ii) (a) LiOH, H2O2, THF, H2O, 94%; (b)
TMSCHN2, MeOH, toluene; (c) TBDMSOTf, 2,6-lutidine, CH2Cl2;
(iii) MeLi, Et2O, –78 °C, 74% for 3 steps; (iv) (a) MEMCl, i-Pr2EtN,
CH2Cl2, 83%, or MOMCl, i-Pr2EtN, CH2Cl2, 91%; (b) TBAF, THF;
(c) TPAP, NMO, CH2Cl2, 90% for 2 steps (13), 68% for 2 steps (14);
(v) (a) OsO4, K2CO3, K3Fe(CN)6, H2O, t-BuOH, pyridine; (b) NaIO4,
NaHCO3, THF, H2O, 76% for 2 steps (R = MEM), 87% for 2 steps (R
= MOM); (c) 15, CH2Cl2, 84% (16), 73% (17).
Attempts to improve the efficiency of the cyclisation by
changing the temperature of the reaction, and the nature
and amount of the proton source, were unsuccessful. In-
Acylation of Evans’ oxazolidinone (n-BuLi, THF, –78 terestingly, when the cyclisation of 16 was carried out at
°C, pentenoyl chloride, 93%) gave literature imide 8.7 Bo- 40 °C, only spirocycle 21a was isolated, although the
ron-mediated, asymmetric aldol reaction8 with aldehyde yield was low (15%). This suggests that retro-aldol frag-
99 then gave the syn adduct 10 in excellent yield. Hydrol- mentation of the spirocycles may play a role in determin-
ysis, ester formation and TBDMS protection of the sec- ing product distribution.
ondary hydroxyl all proceeded efficiently to give 11 that
upon treatment with methyllithium gave 12. Protection of
the tertiary hydroxyl using MEM or MOM chloride,
deprotection of the secondary TBDMS ether, and oxida-
We next studied the behaviour of the free-hydroxyl sub-
strate 20 with SmI2. Pleasingly, exposure of the free-hy-
droxyl substrate 20 to our standard conditions of SmI2 in
THF–MeOH, gave two spirocycle diastereoisomers 24
tion using Ley’s reagent [tetrapropylammonium perruth-
Synlett 2007, No. 20, 3155–3159 © Thieme Stuttgart · New York

LETTER
Sm(II)-Mediated Spirocyclisation
3157
in the cyclisations of 16, 17 and 20 in that only syn diaste-
reoisomers were obtained. Coordination of Sm(III) to the
MEM ether (16), MOM ether (17), and free hydroxyl (20)
substituents appears to have no influence on the stereo-
chemical course of the cyclisation.
O
OBn
O
O
O
RO
i
16/17
BnO
H
OH
OR
21a R = MEM
21b R = MOM
All spirocycles were readily separated by column chroma-
tography. Deprotection of 24 gave crystalline triol 27
O
O
O
whose
structure
was
confirmed
by
X-ray
23a R = MEM
23b R = MOM
crystallography13 (Scheme 6). Thus, spirocycles 21a, 21b
and 24 possess the syn,syn stereochemistry required for
our approach to stolonidiol. The syn,anti stereochemistry
of the spirocycles 22a, 22b and 25 was determined by
NOE experiments on the MOM-protected spirocycle 22b.
BnO
OH
OR
22a R = MEM
22b R = MOM
Scheme 4 Reagents and conditions: (i) SmI2 (4 equiv), THF–
MeOH (4:1), 0 °C, 21a (16%), 22a (16%), 23a (62%), 21b (17%),
22b (18%), 23b (61%).
and 25 now as the major products (1:1 ratio, 51%).12 We
again obtained an uncyclised by-product, however, in this
case, ketone 26 (33%) was isolated resulting from the ret-
ro-aldol reaction of an intermediate Sm(III) alkoxide
(Scheme 5).
O
O
O
i
OBn
20
BnO
H
OH
O
O
OH
26
24
O
Scheme 6 Reagents and conditions: (i) H2, Pd(OH)2/C, EtOH, 97%;
O
(ii) LiAlH4, THF, 54% (unoptimised).
Finally, the lactone ring in spirocycle 24 was reduced with
LiAlH4 to give 5 (R = H), a versatile intermediate in our
approach to stolonidiol and its analogues.
BnO
OH
OH
25
In summary, we have developed an efficient and flexible,
asymmetric route to g,d-unsaturated ketone cyclisation
substrates and have explored their reactivity with SmI2.
Although, the conjugate reduction–aldol spirocyclisation
is less efficient with these more complex substrates, the
spirocyclic products have been obtained in moderate
yield, and an asymmetric synthesis of the cyclopentanol
motif of stolonidiol has therefore been completed.
Scheme 5 Reagents and conditions: (i) SmI2 (4 equiv), THF–
MeOH (4:1), 0 °C, 24 (28%), 25 (23%), 26 (33%).
Carrying out the cyclisation of 20 in the absence of MeOH
at 0 °C or –78 °C led to the isolation of an unsaturated lac-
tone resulting from a retro-aldol reaction of the starting
material. This suggests that conjugate reduction of the un-
saturated lactone group does not occur in the absence of By employing synthetic equivalents for the tertiary hy-
MeOH and that the retro-aldol process dominates. At- droxyl group in 7 that have a reduced steric presence, we
tempts to use nonprotic activators,1b,e such as DMPU, aim to identify substrates that will give improved yields in
HMPA, and Et3N were unsuccessful and led to complex the cyclisation. For example, a preliminary result using a
product mixtures.
protected hydroxymethyl group a to the ketone carbonyl
group in racemic, model substrate 28, gave spirocycle 29
in an excellent yield of 90% (Scheme 7).
It is clear from our studies that increased steric hindrance
around the ketone carbonyl in 16, 17 and 20 (cf 1) makes
the challenging carbon–carbon bond-forming step that We are currently preparing a range of substrates that un-
forms two adjacent quaternary centres, even more diffi- dergo efficient cyclisation and possess a group capable of
cult. Of the four diastereoisomers possible from the cycli- binding Sm(III) and exerting greater control on the stereo-
sation reactions, two were formed in an approximately 1:1 chemical course of the cyclisation.
ratio. We found that deprotection of spirocycle 21a and
21b gave 24, and deprotection of spirocycle 22a and 22b
gave 25. Thus the same sense of selectivity was observed
Synlett 2007, No. 20, 3155–3159 © Thieme Stuttgart · New York

3158
L. A. Sloan et al.
LETTER
O
by opening to air and the addition of NaCl (sat. solution in
H2O, 5 mL). The aqueous layer was separated and extracted
with 60% EtOAc in PE (40–60 °C) (4 × 15 mL). The com-
bined organic extracts were dried (MgSO4), and concen-
trated in vacuo. Purification by column chromatography
[eluting with 30% EtOAc in PE (40–60 °C)], gave
O
O
O
i
OTBDMS
OH
(5R,6R,7S)-6-[2-(benzyloxy)ethyl]-6-hydroxy-7-(1-
hydroxy-1-methylethyl)-2-oxaspiro[4.4]nonan-1-one (24;
O
OTBDMS
28
29
22 mg, 0.06 mmol, 28%) as a clear, colourless oil; [a]20
D
Scheme 7 Reagents and conditions: (i) SmI2 (4 equiv), THF–
–18.1 (c = 1.85, CHCl3). ATR: 3440, 2939, 1729 (s, ester
CO), 1374 (m), 1195 cm–1. 1H NMR (300 MHz, CDCl3): d =
1.16 (s, 3 H, Me), 1.46 (s, 3 H, Me), 1.71–2.01 (m, 5 H, 1 H
of CH2CH, 1 H of CH2CH2CH, 1 H of CH2CH2OBn, 1 H of
CH2CH2OCO, CH), 2.17 (1 H, q, J = 7.2 Hz, 1 H of CH2),
2.28–2.34 (m, 1 H, CH2) 2.41 (1 H, dt, J = 11.4, 2.4 Hz,
CH2CH2OBn), 2.56 (1 H, q, J = 7.8 Hz, 1 H of
MeOH (4:1), 0 °C, 90% (1:1 mixture of diastereoisomers).
Acknowledgment
We thank the EPSRC and GlaxoSmithKline for an Industrial CASE
award (L.A.S), and AstraZeneca and Pfizer for additional untied
funding (D.J.P). We also thank Mark Slater and Matthew Powner
for assistance optimizing the route to 16.
CH2CH2OC=O), 3.52–3.61 (m, 2 H, CH2OBn), 3.96 (1 H,
dt, J = 6.9, 0.9 Hz, 1 H of CH2OC=O), 4.05–4.11 (m, 1 H,
CH2OCO), 4.16 (1 H, OH), 4.23 (d, AB system, J = 8.5 Hz,
1 H, OCH2Ph), 4.26 (d, AB system, J = 8.5 Hz, 1 H,
References and Notes
OCH2Ph), 5.86 (1 H, OH), 7.27–7.34 (m, 5 H, ArCH). 13
NMR (100 MHz, CDCl3): d = 29.9 (CH2CH2OCO), 30.0
C
(1) For recent reviews on the use of samarium(II) iodide, see:
(a) Molander, G. A.; Harris, C. R. Tetrahedron 1998, 54,
3321. (b) Kagan, H.; Namy, J. L. Lanthanides: Chemistry
and Use in Organic Synthesis; Kobayashi, S., Ed.; Springer:
Berlin, 1999, 155. (c) Steel, P. G. J. Chem. Soc., Perkin
Trans. 1 2001, 2727. (d) Kagan, H. B. Tetrahedron 2004,
59, 10351. (e) Dahlén, A.; Hilmersson, G. Eur. J. Inorg.
Chem. 2004, 3393. (f) Edmonds, D. J.; Johnston, D.;
Procter, D. J. Chem. Rev. 2004, 104, 3371.
(2) (a) Johnston, D.; McCusker, C. M.; Procter, D. J.
Tetrahedron Lett. 1999, 40, 4913. (b) Johnston, D.;
McCusker, C. F.; Muir, K.; Procter, D. J. J. Chem. Soc.,
Perkin Trans. 1 2000, 681. (c) Johnston, D.; Francon, N.;
Edmonds, D. J.; Procter, D. J. Org. Lett. 2001, 3, 2001.
(d) Johnston, D.; Couché, E.; Edmonds, D. J.; Muir, K.;
Procter, D. J. Org. Biomol. Chem. 2003, 328. (e) Edmonds,
D. J.; Muir, K. W.; Procter, D. J. J. Org. Chem. 2003, 68,
3190.
(CH2CH2CH), 30.5 (Me), 30.9 (Me), 33.9 (CH2CH2CH),
36.9 (CH2CH2OBn), 54.2 (CqCOO), 55.4 (CH), 65.3
(CH2OBn), 65.4 (CH2OCO), 72.4 (OCH2Ph), 72.5
(CqOHCH2CH2OBn), 86.0 (CqMe2OH), 127.6 (ArCH),
128.2 (4 × ArCH), 138.0 (ArCq), 182.9 (ester CO). MS (CI
mode): m/z (%) = 349 (85) [M+], 331 (40), 308 (40), 219
(100), 195 (50). HRMS: m/z [M + H]+ calcd for C20H29O5:
349.2010; found: 349.2006. Further elution gave (5S,6S,7S)-
6-[2-(benzyloxy)ethyl]-6-hydroxy-7-(1-hydroxy-1-
methylethyl)-2-oxaspiro[4.4]nonan-1-one (25; 18.5 mg,
0.05 mmol, 23%) as a clear, colourless oil; [a]20D –15.9 (c =
1.32, CHCl3). ATR: 2343 (m), 2947 (m), 1744 (s, ester CO),
1453 (m), 1372 (m), 1183 (m) cm–1. 1H NMR (500 MHz,
CDCl3): d = 1.16 (s, 3 H, Me), 1.29 (s, 3 H, Me), 1.53–1.56
(m, 2 H, CH2CH), 1.87–1.91 (m, 2 H, 1 H of CH2CH2CH, 1
H of CH2CH2OCO), 2.03–2.10 (m, 2 H, 1 H of CH2CH2CH,
1 H of CH2CH2OBn), 2.42–2.48 (m, 2 H, 1 H of
CH2CH2OBn, 1 H of CH2CH2OCO), 2.60 (1 H, t, J = 10.0
Hz, CH), 3.62–3.68 (m, 2 H, CH2OBn), 4.01 (dt, J = 2.6, 5.1
Hz, 2 H, CH2OCO), 4.33 (d, AB system, J = 11.6 Hz, 1 H,
OCH2Ph), 4.43 (d, AB system, J = 11.6 Hz, 1 H, OCH2Ph),
7.19–7.40 (m, 5 H, ArCH). 13C NMR (100 MHz, CDCl3):
d = 23.2 (CH2CH2CH), 29.2 (Me), 30.1 (CH2CH2CH), 30.9
(Me), 31.3 (CH2CH2OCO), 33.1 (CH2CH2OBn), 56.2
(CqCOO), 57.4 (CH), 65.2 (CH2OCO), 66.6 (CH2OBn), 72.5
(CqOHCH2CH2OBn), 72.9 (OCH2Ph), 83.9 [CqMe2OH],
127.7 (ArCH), 128.0 (2 × ArCH), 128.3 (2 × ArCH), 137.8
(CqAr), 181.6 (ester CO). MS (CI mode): m/z (%) = 349 (40)
[M+], 313 (100), 307 (100), 291 (30), 225 (35), 221 (40),
200(50), 183 (85), 108 (40). HRMS: m/z [M + H]+ calcd for
C20H29O5: 349.2010; found: 349.2010. Further elution gave
3-[6-(benzyloxy)-4-oxohexyl]dihydrofuran-2 (3H)-one (26;
23 mg, 0.08 mmol, 33%) as a clear, colourless oil. IR (neat):
2918 (m), 2353 (m), 1765 (s, ketone CO), 1710 (s, ester CO),
1371 (m), 1103 (m) cm–1. 1H NMR (300 MHz, CDCl3): d =
1.39–1.48 (m, 1 H, COOCH2CH2], 1.68 (app. pent, J = 5.4
Hz, 2 H, (COCH2CH2CH2CH), 1.80–2.00 (m, 2 H, 1 H of
COCH2CH2, 1 H of COOCH2CH2), 2.34–2.42 (m, 1 H,
COCH2), 2.45–2.54 (m, 3 H, COCHCH2, COCHCH2), 2.69
(t, J = 4.5 Hz, 2 H, BnOCH2CH2), 3.74 (t, J = 4.5 Hz, 2 H,
BnOCH2), 4.16 (dt, J = 5.1, 6.8 Hz, 1 H, COOCH2), 4.32 (dt,
J = 2.1, 6.8 Hz, 1 H, COOCH2), 4.50 (s, 2 H, OCH2Ph),
7.26–7.36 (m, 5 H, ArCH). 13C NMR (100 MHz, CDCl3):
(3) (a) Hutton, T. K.; Muir, K.; Procter, D. J. Org. Lett. 2002, 4,
2345. (b) Hutton, T. K.; Muir, K.; Procter, D. J. Org. Lett.
2003, 5, 4811.
(4) Mori, K.; Iguchi, K.; Yamada, N.; Yamada, Y.; Inouye, Y.
Tetrahedron Lett. 1987, 28, 5673.
(5) Yabe, T.; Yamada, H.; Shimomura, M.; Miyaoka, H.;
Yamada, Y. J. Nat. Prod. 2001, 63, 433.
(6) Miyaoka, H.; Baba, T.; Mitome, H.; Yamada, Y.
Tetrahedron Lett. 2001, 42, 9233.
(7) Kamenecka, T. M.; Danishefsky, S. J. Angew. Chem. Int. Ed.
1998, 37, 2995.
(8) Evans, D. A.; Bartroli, J.; Shih, T. L. J. Am. Chem. Soc.
1981, 103, 2127.
(9) Oxidation of commercially available 3-benzyloxypropan-1-
ol gave 9 (py·SO3, DMSO, Et3N, CH2Cl2, 78%).
(10) Ley, S. V.; Norman, J.; Griffith, W. P.; Marsden, S. P.
Synthesis 1994, 639.
(11) Yu, W.; Mei, Y.; Kang, Y.; Hua, Z.; Jin, Z. Org. Lett. 2004,
6, 3217.
(12) Anhydrous MeOH (4.34 mL) was added to a stirred solution
of SmI2 (0.1 M in THF, 9.20 mL, 0.92 mmol, 4 equiv) at 0 °C
and the solution was stirred for 10 min. (3E)-3-[(3S)-6-
(Benzyloxy)-3-(1-hydroxy-1-methylethyl)-4-oxohexyl-
idene]dihydrofuran-2 (3H)-one (20; 100 mg, 0.23 mmol, 1.0
equiv) in THF (1.5 mL) was added and the resultant solution
was stirred at 0 °C for 0.5 h before the reaction was quenched
Synlett 2007, No. 20, 3155–3159 © Thieme Stuttgart · New York

LETTER
Sm(II)-Mediated Spirocyclisation
3159
d = 21.1 (COCH2CH2CH2), 28.5 (OCH2CH2), 29.7
(COCH2), 39.2 (CH), 42.8 (CH2CHCO), 42.9
m/z [M + NH4]+ calcd for C17H26O4N: 308.1856; found:
308.1859.
(CH2CH2OBn), 65.3 (CH2OBn), 66.5 (CH2OCO), 73.2
(OCH2Ph), 127.7 (3 × ArCH), 128.4 (2 × ArCH), 138.0
(ArCq), 179.2 (ester CO), 208.6 (ketone CO). MS (CI mode):
(13) CCDC 605754 contains the supplementary crystallographic
data for this paper (compound 27). These data can be
obtained free of charge from The Cambridge
Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
+
m/z (%) = 309 (20) [MNH4 ], 308 (100), 291 (10). HRMS:
Synlett 2007, No. 20, 3155–3159 © Thieme Stuttgart · New York

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