Synthesis of highly oxygenated enantiomerically pure cis-bicyclo[4.3.0]nonanes from secondary sugar allyltin derivatives

Article abstract of DOI:10.1016/S0957-4166(03)00310-0

Secondary sugar allyltin derivatives of the D-series: Sug-CH(SnBu₃)-CH=CH₂ (obtained in an S_N2′ reaction of the corresponding primary allylic mesylates with 'Bu₃SnCu') with the S-configuration at the stereogenic

Full text of DOI:10.1016/S0957-4166(03)00310-0

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 14 (2003) 1709–1713
Synthesis of highly oxygenated enantiomerically pure
cis-bicyclo[4.3.0]nonanes from secondary sugar allyltin
derivativesꢀ
Sławomir Jarosz,* Katarzyna Szewczyk and Anna Zawisza†
Institute of Organic Chemistry, Polish Academy of Sciences Kasprzaka, 44, 01-224 Warszawa, Poland
Received 7 March 2003; accepted 3 April 2003
Abstract—Secondary sugar allyltin derivatives of the
D
-series: Sug-CH(SnBu3)-CHꢀCH2 (obtained in an SN2% reaction of the
corresponding primary allylic mesylates with ‘Bu3SnCu’) with the S-configuration at the stereogenic center bearing the -SnBu3
group decompose at 140°C to dienoaldehydes: CH2ꢀCH-CHꢀCH-[(CHOR)3]-CHO with the cis geometry across the internal
double bond. Such aldehydes react with the stabilized Wittig reagents to afford trienes, cyclization of which provides highly
oxygenated enantiomerically pure cis-bicyclo[4.3.0]nonenes. This methodology is complementary to that recently proposed by us
leading to such bicyclic systems, but with the trans junction between the five- and six-membered rings. © 2003 Elsevier Science
Ltd. All rights reserved.
1. Introduction
Stereoselective [4+2] cyclization of trienes 3 provides
highly oxygenated bicyclo[4.3.0]nonanes 4 with a trans
ring-junction; the geometry of the bicyclic product 4
arises from the endo transition state of this IMDA
process (Scheme 1).4
Carbobicyclic compounds (bicyclo[4.3.0]nonanes and
bicyclo[4.4.0]decanes) are interesting synthetic targets.
One of the most useful routes leading to such deriva-
tives consists of an intramolecular Diels–Alder reaction
of the corresponding trienes, e.g. 3 (Scheme 1).2 They
may be prepared from appropriate dienoaldehydes, e.g.
2, by reaction with ylides. We have previously reported,
that dienes 2 with the trans configuration across the
internal double bond are conveniently prepared by
controlled decomposition of the primary sugar allyltins
1 with a Lewis acid (Scheme 1).3
The alternative perhydroindane with the cis ring-junc-
tion should be prepared from the dienoaldehyde with
the opposite cis-configuration across the internal dou-
ble bond if the endo transition state is assumed.
Recently we have found, that such cis-dienes are
formed during thermal decomposition of secondary
sugar allyltins1 obtained by reaction of sugar allylic
Scheme 1. Reagents and conditions: i. Ref. 3; ZnCl2, methylene chloride, rt, 2 h; ii. Ref. 4; Ph3PꢀCHCOR; then cyclization.
ꢀ See Ref. 1.
* Corresponding author. Fax: (+48-22) 632-66-81; e-mail: sljar@icho.edu.pl
† Fellow of the Foundation for Polish Science: in-country outgoing fellowship. Present address: Department of Organic and Applied Chemistry,
Ło´dz´ University, Narutowicza 68, 90-136 Ło´dz´, Poland.
0957-4166/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0957-4166(03)00310-0

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S. Jarosz et al. / Tetrahedron: Asymmetry 14 (2003) 1709–1713
mesylates (or bromides) with tri-n-butyltin cuprate.3,5
Herein, application of secondary sugar allyltins in stereo-
controlled synthesis of highly oxygenated bicy-
clo[4.3.0]nonanes with the cis junction between the
carbocyclic rings is reported.
As shown in Scheme 2, the synthesis of bicy-
clo[4.3.0]nonene system from the cis-dienoaldehyde 7a
is complementary to that demonstrated previously by
us (route a in Scheme 2) leading to the bicyclic deriva-
tive 2a with the trans ring-junction.4
The
-manno-configurated derivative 6b5 behaved simi-
D
larly. Its thermal decomposition at 140°C provided the
cis-dienoaldehyde 7b; the coupling constant J5,6=10.1
Hz observed in the spectrum of acetate 8b confirmed
the geometry of the internal double bond. When the
decomposition experiment was conducted in the pres-
ence of Ph3PꢀCHCO2Me the tandem Wittig/Diels–
Alder reaction occurred affording the cis-bicyclo
[4.3.0]nonene derivative 10b as a mixture of two
stereoisomers in the ratio 6:1 (Scheme 3).
2. Thermal reaction of secondary sugar allyltin
derivatives with ylides: synthesis of highly oxygenated
cis-bicyclo[4.3.0]perhydroindanes
Secondary
D-gluco-configurated sugar allylltin deriva-
tive 6a was obtained by the SN2% reaction of the corre-
sponding allylic mesylate 5a with the soft nucleophile
tri-n-butyltin cuprate (‘Bu3SnCu’).6 This process was
highly stereoselective; only one isomer of 6 was
produced3 with the S-configuration at the newly cre-
ated stereogenic center.5
The configurations of both stereoisomers were estab-
lished on the basis of the NOESY correlation spectra.
In both compounds the strong H1–H6 correlations
indicated the cis-junction between the five- and six-
membered rings. In the spectrum of 10b the correlation
between H-6 and H-7 was observed, thus establishing
the 6S configuration. In the spectrum of the minor
isomer 10b% the NOE effect between H-1 and H-9
indicated the 1R configuration.
Compound 6 decomposed at high temperature (140°C)
to dienoaldehyde 7a with the cis-geometry across the
1
internal double bond as determined from the H NMR
spectrum of its derivative 8a (Scheme 2).
The aldehyde formed by thermal decomposition of the
appropriate allyltin could be either isolated pure or
react in situ with ylides, thus forming trienes, e.g. 9a
(Scheme 2), which may further undergo cyclization.
Indeed, thermal decomposition of 6a performed in the
presence of methoxycarbonylmethylene triphenylphos-
phorane provided the cis-perhydroindene 10a as the
only isomer in good yield.1 Configuration of this
The high cis selectivity of the cyclization might be
explained assuming an endo transition state. The pre-
ferred transition state (A in Fig. 1) in the cyclization of
the triene 9a should lead to the bicyclic isomer 10a with
the cis ring-junction. The other possible transition state
(B in Fig. 1) is disfavored, because of two severe steric
interactions and, therefore, the alternative cis-perhy-
droindene (10a%) is not formed.
1
derivative was assigned from the H NMR (NOESY)
experiments. The strong NOE correlation between H-1
and H-6 indicated the cis ring-junction, while correla-
tions H6–H8, H5–H7, and H5–H9 indicated the 5S,6S
and consequently 1S configurations in 10a (see Scheme
2 and Section 4).
The situation is similar with 9b. Again the transition
state C (Fig. 2) is preferred providing the perhydroin-
dene derivative 10b with the same (as in 10a) configura-
Scheme 2. Reagents and conditions: i. ‘Bu3SnCu’; ii. xylene (140°C), 3 h; iii. NaBH4, then Ac2O; iv. ZnCl2; v. 140°C,
Ph3PꢀCHCO2Me.

S. Jarosz et al. / Tetrahedron: Asymmetry 14 (2003) 1709–1713
1711
Scheme 3. Reagents and conditions: i. Boiling xylene (140°C), 4 h; ii. NaBH4, then Ac2O; iii. boiling xylene, Ph3PꢀCHCO2Me, 3–4 h.
Figure 1. The transition states in the intramolecular cyclization of the triene 9a.
Figure 2. The transition states in the intramolecular cyclization of the triene 9b.

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S. Jarosz et al. / Tetrahedron: Asymmetry 14 (2003) 1709–1713
tion at the ring junction. However, the alternative
endo-transition state (D in Fig. 2) is less disfavored
(than B in Fig. 1) and the alternative 1R,6R isomer is
formed in significant amounts.
the mixture was kept at rt for 30 min. It was then
concentrated in vacuum and the product was isolated by
column chromatography (hexane–ethyl acetate, 10:1).
From 6a acetate 8a was obtained in 77% yield (374 mg)
and from 6b compound 8b in 78% yield (379 mg).
3. Summary
4.2.1. (2S,3S,4R,Z)-1-Acetoxytribenzyloxyocta-5,7-diene
1
8a. [h]2D0=−9.4 (c 1.3, CHCl3). H NMR l: 6.66 (ddd,
The secondary sugar allyltin derivatives of the
D
-series,
H-7), 6.27 (dd, J6,7 11.5 Hz, H-6), 5.49 (dd, J5,6 10.8 Hz,
H-5), 5.28 (dd, J6,8b 0.9, J7,8b 16.7 Hz, H-8b) 5.14 (d,
J7,8a 10.0 Hz, H-8a), 4.82 and 4.70 (AB, J 11.4 Hz,
CH2Ph), 4.64 (dd, J4,5 9.5 Hz, H-4), 4.59 and 4.36 (AB,
J 11.7 Hz, CH2Ph), 4.57 and 4.51 (AB, J 11.6 Hz,
CH2Ph), 4.22 (dd, J1a,2 4.9 Hz, H-1a), 4.13 (dd, J1a,1b
11.6, J1b,2 5.9 Hz, H-1b), 3.79 (ddd, H-2), 3.61 (dd, J2,3
4.6, J3,4 5.7 Hz, H-3), 1.95 [s, OC(O)CH3]. 13C NMR l:
170.5 [OC(O)CH3], 138.4, 138.3, 138.2 (3×Cquat benzyl),
133.7 (C-6), 131.8 (C-7), 128.6 (C-5), 120.0 (C-8), 81.0
(C-3), 77.5 (C-2), 75.0 (C-4), 75.0, 73.0 and 70.5 (3×
CH2Ph), 63.7 (C-1), 20.8 [OC(O)CH3]. Anal. calcd for
C31H34O5: C, 76.51; H, 7.04. Found: C, 76.26; H, 7.18.
with the S-configuration at the stereogenic center bear-
ing the -SnBu3 group decompose at 140°C affording the
dienoaldehydes with the cis-configuration across the
internal double bond. If the thermal decomposition is
conducted in the presence of Ph3PꢀCHCO2Me, the
dienaldehydes react with the ylide providing the corre-
sponding trienes, which in situ undergo cyclization to
cis-perhydroindenes in good yields. The method pre-
sented in this paper is complementary to that reported
previously by us, which allows preparation of the bicy-
clo[4.3.0]nonenes with the trans ring-junction between
both rings.
4.2.2.
(2R,3S,4R,Z)-1-Acetoxytribenzyloxyocta-5,7-
1
4. Experimental
4.1. General
diene 8b. [h]2D0=−2.4 (c 0.85, CHCl3). H NMR l: 6.58
(ddd, H-7), 6.25 (dd, J6,7 11.2 Hz, H-6), 5.55 (dd, J5,6
10.1 Hz, H-5), 5.29 (d, J7,8b 16.7 Hz, H-8b), 5.19 (d, J7,8a
10.3 Hz, H-8a), 4.73 and 4.65 (AB, J 11.3 Hz, CH2Ph),
4.62 and 4.31 (AB, J 11.9 Hz, CH2Ph), 4.57 (dd, J4,5 8.8
Hz, H-4), 4.54 and 3.35 (AB, J 11.4 Hz, CH2Ph), 4.52
(dd, J1a,1b 12.1, J1b,2 2.8 Hz, H-1b), 4.17 (dd, J1a,2 5.3
Hz, H-1a), 3.86 (ddd, J2,3 6.2 Hz, H-2), 3.67 (dd, J3,4 4.3
Hz, H-3), 1.99 [s, OC(O)CH3]. 13C NMR l: 170.8
[OC(O)CH3], 138.3, 138.2, 138.1 (3×Cquat benzyl), 133.3
(C-6), 131.8 (C-7), 129.2 (C-5), 119.9 (C-8), 81.5 (C-3),
77.0 (C-2), 74.2 (C-4), 75.0, 72.1 and 70.3 (3×CH2Ph),
63.2 (C-1), 20.9 [OC(O)CH3]. Anal. calcd for C31H34O5:
C, 76.51; H, 7.04. Found: C, 76.57; H, 6.82.
Optical rotations were measured with a JASCO DIP 360
automatic polarimeter at 20 2°C. NMR spectra were
recorded with Bruker AM-500 (500 MHz) specrometer
in CDCl3 solutions with Me4Si as an internal standard.
1H and 13C signal of aromatic groups occurred at the
expected chemical shifts were omitted in the description
of spectra. 13C NMR spectra were recorded in the
DEPT 135 mode. The proton and carbon resonances in
8a,b and 10a,b,b% were assigned by the COSY and
HETCOR correlations. Mass spectra (LSIMS, positive
mode) were recorded on an AMD-604 mass spectrome-
ter. HPLC was carried out on a Shimadzu instrument:
central unit C-R4A, pump unit LC-8A, UV detector
SPD-6A on a column Machery Nagel Nucleosil 100-7.
TLC was performed on silica gel HF-254 ready plates
and column chromatography on silica gel 230–400 or
70–230 mesh (E. Merck). Organic solutions were dried
over anhydrous magnesium or sodium sulfate.
4.3. Decomposition of secondary sugar allyltins in the
presence of Ph3PꢀCHCO2Me
To a solution of allyltin 6a or 6b (763 mg, 1 mmol) in
dry xylene (10 mL) Ph3PꢀCHCO2Me (500 mg, 1.5
mmol) was added and the mixture was boiled under
reflux for 3–4 h. It was then cooled to room tempera-
ture, concentrated and the product was isolated by
column chromatography (hexane–ethyl acetate, 10:1)
and further purified by HPLC (hexane–ethyl acetate,
20:1). From 6a compound 10a was obtained in 75%
yield (373 mg). Reaction of 6b afforded two stereoiso-
mers: 10b (66%, 328 mg) and 10b% (11%, 54 mg).
4.2. Thermal decomposition of secondary sugar allyltin
derivatives
A solution of the corresponding allyltin derivative 6a or
6b (763 mg, 1 mmol) was dissolved in dry xylene (5 mL)
and boiled under reflux until TLC (hexane–ethyl ace-
tate, 5:1) indicated disappearance of the starting mate-
rial and formation of a new more polar product (2–3 h).
The mixture was cooled to room temperature, concen-
trated and the residue was dissolved in methanol/water
(5:1 v/v, 6 mL). Sodium borohydride (50 mg) was added
and the mixture was stirred for 30 min at room temper-
ature. Water (10 mL) was added, the organic phase was
separated, dried, and concentrated to ca half of the
volume. To a residue (co-evaporated twice with toluene)
pyridine (4 mL) and acetic anhydride (2 mL) were added
followed by a catalytic amount of DMAP (20 mg) and
4.3.1. (1S,5S,6S,7S,8S,9R)-Tribenzyloxy-5-methoxycar-
bonylbicyclo[4.3.0]non-2-ene 10a. [h]2D0=+63.1 (c 0.6,
CHCl3). H NMR l: 5.72 (m, J2,3 10.1 Hz, H-2), 5.65
1
(m, H-3), 4.59 (m, 3×CH2Ph), 4.04 (dd, J8,9 5.0 Hz,
H-8), 3.69 (dd, J6,7 11.5, J7,8 5.5 Hz, H-7), 3.66 (m, H-9),
3.62 [s, C(O)OCH3], 2.79 (m, H-1) 2.68 (ddd, J4b,5 6.0,
J5,6 7.5 Hz, H-5), 2.64 (ddd, J1,6 5.4 Hz, H-6), 2.29 (m,
J4a,4b 17.7 Hz, H-4b), 1.99 (m, H-4a). 13C NMR l: 175.4
[C(O)OCH3], 138.5, 138.3, 138.2 (3×Cquat benzyl), 127.8
(C-2), 124.8 (C-3), 90.3 (C-8), 88.4 (C-7), 83.0 (C-9),
72.1, 71.8, 71.5 (3×CH2Ph), 51.7 [C(O)OCH3],

S. Jarosz et al. / Tetrahedron: Asymmetry 14 (2003) 1709–1713
1713
40.6 (C-6), 39.9 (C-1), 38.5 (C-5), 25.1 (C-4). NOESY:
References
H1–H6, H9–H5, H6–H8, H5–H7. HRMS m/z:
521.23039 [C32H34O5Na (M+Na+) requires 521.23364].
Anal. calcd for C32H34O5: C, 77.08; H, 6.87. Found: C,
77.04; H, 6.80.
1. Preliminary communication: Jarosz, S.; Szewczyk, K. Tetra-
hedron Lett. 2001, 42, 3021–3024.
2. For examples of the application of IMDA in the synthesis
of carbobicyclic products, see: (a) Fraser-Reid, B.; Benko,
Z.; Guiliano, R.; Sun, K. M.; Taylor, N. J. Chem. Soc.,
Chem. Commun. 1984, 1029–1030; (b) Carruthers, W.
Cycloaddition Reactions in Organic Synthesis (Tetrahedron
Organic Chemistry Series Vol. 8) 1990, 91–208; (c) Roush,
W. R. Advances in Cycloaddition 1990, 2, 91–146 (Curran,
D. P., Ed.) and references cited therein; (d) Herczegh, P.;
Zsely, M.; Szilagyi, L.; Bajza, I.; Kovacs, A.; Batta, G.;
Bognar, R. Cycloaddition Reactions in Organic Chemistry
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Chem. 1991, 56, 2826–2837; (f) Craig, D.; Geach, N. J.;
Pearson, Ch. J.; Slawin, A. M. Z.; White, A. J. P.; Williams,
D. J. Tetrahedron 1995, 51, 6071–6098; (g) Ishikara, K.;
Kurihara, H.; Yamamoto, H. J. Am. Chem. Soc. 1996, 118,
3049–3050; (h) Ainsworth, P. J.; Craig, D.; White, A. J. P.;
Williams, D. J. Tetrahedron 1996, 52, 8937–8946; (i)
Deagostino, A.; Maddaluno, J.; Prandi, C.; Venturello, P.
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Sakata, S. T.; Shea, K. J. J. Org. Chem. 1996, 61, 7438–7451;
(k) Diedrich, M. K.; Klaerner, F.-G. J. Am. Chem. Soc.
1998, 120, 6212–6218; (l) Evans, D. A.; Barnes, D. M.;
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J. Am. Chem. Soc. 1999, 121, 7582–7594; (m) Fukunaga, K.;
Kunieda, T. Tetrahedron Lett. 1999, 40, 6041–6044; (n)
Jung, M. E.; Huang, A. Org. Lett. 2000, 2, 2659–2662; (o)
Enholm, E. J.; Jiang, Sh. J. Org. Chem. 2000, 65, 4756–4758;
(p) Hayashi, H. In Cycloaddition Reactions in Organic
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VCH: New York, 2002; pp. 5–55.
4.3.2.
(1S,5S,6S,7R,8S,9R)-7,8,9-Tribenzyloxy-5-
methoxycarbonylbicyclo[4.3.0]non-2-ene 10b. [h]2D0=
1
+106.4 (c 1.1, CHCl3). H NMR l: 5.83 (m, J2,3 9.8,
J1,2ꢀJ2,4a 3.0 Hz, H-2), 5.75 (m, H-3), 4.76 and 4.64
(AB, J 12.0 Hz, CH2Ph), 4.62 and 4.49 (AB, J 11.6 Hz,
CH2Ph), 4.59 and 4.54 (AB, J 11.7 Hz, CH2Ph), 4.08
(dd, J7,8 5.2, J6,7 6.2 Hz, H-7), 3.90 (dd, H-8), 3.77 (dd,
J1,9 6.8, J8,9 3.6 Hz, H-9), 3.44 [s, C(O)OCH3], 2.95
(ddd, J4a,5 11.0, J4b,5 4.7 Hz, H-5), 2.88 (ddd, J1,6 8.5,
J5,6 11.6 Hz, H-6), 2.45 (m, H-1), 2.27 (ddd, J4a,4b 16.6,
J3,4b 5.3 Hz, H-4b), 1.99 (m, H-4a). 13C NMR l: 177.0
[C(O)OCH3], 2×138.7, 138.3 (3×Cquat benzyl), 127.8
(C-3), 125.5 (C-2), 87.8 (C-9), 83.7 (C-8), 80.1 (C-7),
73.0, 72.5, 72.3 (3×CH2Ph), 51.2 [C(O)OCH3], 41.0
(C-1), 39.7 (C-6), 38.5 (C-5), 28.0 (C-4). NOESY: H1–
H6, H6–H7. Anal. calcd for C32H34O5: C, 77.08; H,
6.87. Found: C, 77.01; H, 6.83.
4.3.3.
(1R,5R,6R,7R,8S,9R)-7,8,9-Tribenzyloxy-5-
methoxycarbonylbicyclo[4.3.0]non-2-ene 10b%. [h]2D0=
−48.4 (c 0.7, CHCl3). 1H NMR l: 5.80 (m, J2,3 10.1 Hz,
H-3), 5.74 (m, H-2), 4.25 (m, 3×CH2Ph), 4.08 (dd, J1,9
6.9, J8,9 4.2 Hz, H-9), 3.87 (dd, J8,7 5.0 Hz, H-8), 3.81
(dd, J6,7 5.2 Hz, H-7), 3.64 [s, C(O)OCH3], 3.06 (m,
H-1), 2.63 (m, J1,6ꢀJ5,6 8.8 Hz, H-6), 2.52 (m, J5,4a 8.2,
J5,4b 5.4 Hz, H-5), 2.27 (m, J4a,4b 17.2, J2,4b 2.9 Hz,
H-4b), 2.13 (m, J2,4a 1.8 Hz, H-4a). 13C NMR l: 175.7
[C(O)OCH3], 138.5, 138.4, 138.3 (3×Cquat benzyl), 126.0
(C-3), 125.7 (C-2), 83.5 (C-9), 81.4 (C-8), 80.7 (C-7),
72.1, 72.0, 71.7 (3×CH2Ph), 51.7 [C(O)OCH3], 42.1
(C-6), 41.4 (C-5), 37.2 (C-1), 26.0 (C-4). NOESY: H1–
H6, H1–H9, H5–H7. HRMS m/z: 521.23313
[C32H34O5Na (M+Na+) requires 521.23364].
3. Jarosz, S. Tetrahedron 1997, 53, 10765–10774.
4. (a) Jarosz, S.; Kozłowska, E.; Jez; ewski, A. Tetrahedron
1997, 53, 10775–10782; (b) Jarosz, S.; Sko´ra, S. Tetrahedron:
Asymmetry 2000, 11, 1425–1432.
5. Jarosz, S.; Szewczyk, K.; Zawisza, A. Tetrahedron: Asymme-
try, next paper.
Acknowledgements
6. Lipshutz, B. H.; Ellsworth, E. L.; Dimock, S. H.; Reuter,
D. C. Tetrahedron Lett. 1989, 30, 2065–2068; although we
depicted this reagent as ‘Bu3SnCu’ the nature of this species
is much more complicated and its structure according to
Lipshutz should be written as Bu(Bu3Sn)Cu(CN)Li2.
This work was supported by Grant No. 4 T09A 107 23
from the State Committee for Scientific Research,
which is gratefully acknowledged.