7566
B. Leroy / Tetrahedron Letters 46 (2005) 7563–7566
reaction temperature was found to have negligible influ-
ence on the yield and the diastereoselectivity of the pro-
cess. Therefore, we decided to pursue our investigations
2. (a) Kupchan, S. M.; Hemingway, R. J.; Werner, D.; Karim,
A.; McPhail, A. T.; Sim, G. A. J. Am. Chem. Soc. 1968, 90,
3596; (b) Kupchan, S. M.; Hemingway, R. J.; Werner, D.;
Karim, A. J. Org. Chem. 1969, 34, 3903.
7
with the mixture of cis and trans cyclopropanes 10.
3
. Leroy, B. Tetrahedron Lett. 2005, 46, 3025; For similar
reactions using (cyclopropyl)methylsilanes, see: Yadav, V.
K.; Balamurugan, R. Org. Lett. 2003, 5, 4281.
In order to determine the scope of this new transforma-
tion, the ring-opening/aldol reaction sequence was car-
ried out in the presence of various aldehydes and
ketones (Table 1). Aliphatic or aromatic aldehydes
proved to be suitable substrates for this transformation
4
5
. Villieras, J.; Rambaud, M. Org. Synth. 1988, 66, 220.
. Fouquet, E.; Gabriel, A.; Maillard, B.; Pereyre, M. Bull.
Soc. Chim. Fr. 1995, 132, 590.
6. The diastereoisomeric relationship for aldol products was
assigned on the basis of the frequency of resonance for the
hydrogen vicinal to the hydroxyl group, which is consis-
tently higher for the syn isomer than for the anti one.
(
1
entries 1–2), as were dialkyl ketones (entry 3). Alcohols
3–15 were obtained in excellent yields. More interest-
ingly, cyclic ketones were found to smoothly undergo al-
dol condensation, providing an entry towards 5-, 6- and
7
. The absence of influence of the cyclopropane geometry was
already observed for aldol reactions with (cycloprop-
yl)methylstannane 1. However, for this substrate, an
important temperature effect on the diastereoselectivity
was observed (see Ref. 3).
7
-membered derivatives 16–18 (entries 4–6).
With various aldol products in hand, the lactonisation
step was finally investigated. Initial attempts under basic
conditions proved unsuccessful. In contrast, treatment
of linear compounds 12–15 with catalytic amounts of
PTSA in refluxing benzene led to the isolation of exo-
methylene-d-valerolactones 19–22 in quantitative yields
after simple basic work-up (Table 2, entries 1–4). Much
to our delight, the lactonisation of cyclic derivatives 16–
8
9
. To the best of our knowledge, only one example of such
exo-methylene spirolactone has been reported in the liter-
ature: Hon, Y.-S.; Liu, Y.-W.; Hsieh, C.-H. Tetrahedron
2004, 60, 4837.
. Typical experimental procedure. Preparation of 16: To a
solution of (cyclopropyl)methylstannane 10 (100 mg,
0
.204 mmol) and cyclopentanone (21 mg, 0.246 mmol) in
dry diethyl ether (4 mL) at 0 ꢁC was added TiCl (410 lL,
.410 mmol, 1 M solution in dichloromethane). The reac-
4
1
8 proved to be equally efficient and gave access to
0
unique spiro derivatives 23–25, possessing a 5–6, 6–6
tion mixture was stirred at 0 ꢁC for 2 h, then was diluted
with dichloromethane (20 mL) and quenched with satu-
8
and 7–6 bicyclic structure, respectively (entries 5–7).
3
rated NaHCO (20 mL). The aqueous layer was separated
In summary, we have developed an efficient method
for the synthesis of functionalised exo-methylene-d-
valerolactones, involving a one-pot ring-opening/aldol
condensation of a new (cyclopropyl)methylstannane
and extracted with dichloromethane (2 · 20 mL). The
combined organic layers were dried (MgSO ) and evapo-
4
rated in vacuo. The residue was purified by column-
chromatography (silica gel, petroleum ether–diethylether,
1
9
2:1) to give 16 as a colourless oil (46 mg, 79%). H NMR
derivative, followed by an acid-catalysed lactonisation.
(
300 MHz, CDCl
3
) 6.12 (1H, d, J = 1.9 Hz), 5.55 (1H, s),
An easy access to new spiro compounds of various ring-
sizes has also been delineated. Current efforts are now
focusing on the application of this methodology to the
synthesis of natural products of biological interest.
4
.20 (2H, q, J = 7.6 Hz), 4.10 (2H, q, J = 6.7 Hz), 3.00 (1H,
broad s), 2.69–2.78 (3H, m), 1.51–1.96 (8H, m), 1.30 (3H, t,
13
J = 6.7 Hz), 1.21 (3H, t, J = 7.6 Hz). C NMR (63 MHz,
CDCl
3
) 175.79, 166.58, 138.25, 126.55, 82.10, 60.70, 60.42,
3.29, 40.18, 37.41, 31.78, 23.79, 14.17. IR (film) 3519,
962, 2873, 1727, 1714, 1631, 1373, 1146, 1027. MS (APCI)
m/z: 284.7 (M+H , 2), 220.9 (65), 192.9 (95), 165.0 (40),
47.0 (53), 119.0 (100). Preparation of 23: To a solution of
5
2
+
Acknowledgements
1
The author is grateful to Professor I. E. Mark o´ for sup-
port and helpful suggestions. Financial support of this
work by the Fonds National de la Recherche Scientifi-
que (B.L., charg e´ de recherche FNRS) and the Univer-
sit e´ catholique de Louvain is gratefully acknowledged.
alcohol 16 (37 mg, 0.130 mmol) in benzene (6 mL) was
added monohydrated PTSA (2 mg). The reaction mixture
was refluxed for 2 h, then was diluted with dichlorometh-
ane (20 mL) and quenched with saturated NaHCO
20 mL). The aqueous layer was separated and extracted
with dichloromethane (2 · 20 mL). The combined organic
layers were dried (MgSO ) and evaporated in vacuo to give
3 as a colourless oil (32 mg, 100%). H NMR (300 MHz,
CDCl ) 6.48 (1H, s), 5.61 (1H, s), 4.16 (2H, q, J = 7.6 Hz),
3
(
4
1
2
References and notes
3
2
.83–2.98 (3H, m), 1.60–2.01 (8H, m), 1.25 (3H, t,
1
3
1
. For excellent reviews, see: (a) Grieco, P. A. Synthesis 1975,
7; (b) Gammill, R. B.; Wilson, C. A.; Bryson, T. A. Synth.
J = 7.6 Hz). C NMR (63 MHz, CDCl ) 171.32, 164.86,
3
6
131.76, 128.65, 91.75, 61.14, 45.78, 38.71, 36.05, 28.47,
Commun. 1975, 5, 245; (c) Hoffmann, H. M. R.; Rabe, J.
Angew. Chem., Int. Ed. Engl. 1985, 24, 94; (d) Petragnani,
N.; Ferraz, H. M. C.; Silva, G. V. J. Synthesis 1986, 157.
23.60, 23.54, 14.09. IR (film) 3434, 2964, 2876, 1731, 1627,
1306, 1182. MS (APCI) m/z: 238.9 (M+H , 100), 224.8
(35), 192.9 (45).
+
Leroy, Bernard
