Cyclocarbonylation of silicon tethered enynes derived from propargylic alcohols and vinylsilanes: A new reductive Pauson-Khand reaction with a traceless tether

Article abstract of DOI:10.1016/S0040-4039(02)00634-2

In nitrile solvents vinylsilyl ethers of propargylic alcohols undergo Pauson-Khand reaction with polysiloxane extrusion and concomitant reduction of the propargylic C-O bond. The product enones are formally the result of an intermolecular PKR reaction with ethylene.

Full text of DOI:10.1016/S0040-4039(02)00634-2

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 3739–3741
Cyclocarbonylation of silicon tethered enynes derived from
propargylic alcohols and vinylsilanes: a new reductive
Pauson–Khand reaction with a traceless tether
John F. Reichwein, Scott T. Iacono, Mittun C. Patel and Brian L. Pagenkopf*
Department of Chemistry and Biochemistry, The University of Texas at Austin, Austin, TX 78712, USA
Received 18 February 2002; accepted 25 March 2002
Abstract—In nitrile solvents vinylsilyl ethers of propargylic alcohols undergo Pauson–Khand reaction with polysiloxane extrusion
and concomitant reduction of the propargylic CꢀO bond. The product enones are formally the result of an intermolecular PKR
reaction with ethylene. © 2002 Elsevier Science Ltd. All rights reserved.
The isoprostanes (e.g. 4) are receiving considerable
attention for their ability to mimic the biological activ-
ity of the prostaglandins.1 It seemed that a Pauson–
Khand reaction with a silicon tethered2 enyne 1 suitably
functionalized at R1 and R2 could provide an enan-
tioselective and efficient route to the isoprostane core
(Scheme 1). While the Pauson–Khand reaction (PKR)
is a popular strategy for cyclopentenone synthesis,3 the
utilization of vinyl silanes as the olefinic component in
this reaction has seen little use. In this regard, Saigo
reported that under standard Pauson–Khand condi-
tions 3-sila-1,7-enynes undergo cycloisomerization to
eight-membered cyclic dienylsilanes (5“6, Scheme 2),
but cyclopentenones 7 were not detected.4
enones of general structure 3 has not been fully
explored.
Enyne 8, an internal alkyne with an aliphatic sub-
stituent at the propargylic position, was selected as a
model substrate for the isoprostane synthesis (Scheme
3). Enyne 8 was readily prepared by silylation of the
corresponding alcohol (Et3N, CH2Cl2, 0°C to rt, >85%
yield) with commercially available Me2SiCl(CHꢁCH2).
In the initial experiments to identify optimum condi-
tions for the PKR, many experimental variants were
explored, including the use of catalytic7–10 conditions
and the addition of adjuncts reported to facilitate the
PKR: silica,11 amine N-oxides,12 DMSO,13 primary
amines,14 molecular sieves,15 sulfides16 and oxygen.
However, none of these methods provided the desired
cyclopentenone 9, but instead metal decomplexation,
hydrolysis of the silyl ether and/or decomposition
occurred. In contrast, the use of damp nitrile solvents
had a dramatic effect on the course of the reaction, and
in refluxing acetonitrile (30 min) the Co2(CO)6 complex
of enyne 8 was converted to enone 10 in 62% isolated
yield.17,18 The beneficial effect of nitrile solvents on the
At the onset of this project the prospect of the 4-sila-
cyclopentenones undergoing Lewis acid-catalyzed desil-
ylation was an obvious potential challenge to the
successful implementation of the strategy outlined in
Scheme 1.5 Structurally related enones have been pre-
pared by Whitby through a zirconocene-mediated
cyclization/carbonylation sequence,6 but the general
effectiveness of the Tamao–Fleming oxidation with
Scheme 1.
* Corresponding author.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00634-2

3740
J. F. Reichwein et al. / Tetrahedron Letters 43 (2002) 3739–3741
bons bound to the silicon tether were reduced during
the course of the reaction. This new method offers a
convenient alternative to the intermolecular Pauson–
Khand reaction with ethylene gas. In these reactions,
the reduction of the propargylic oxygen indicates a
process more complicated than mere Lewis acid medi-
ated desilylation. Further details providing insight into
Scheme 2.
Table 1. Pauson–Khand reaction of vinylsilane-derived
1 eq Co2(CO)8
Ph
enynesa
O
Si
Me2
MeCN, 1% H2O
reflux
8
(62%)
nPr
nPr
Ph
O
O
O
Si
Me2
Ph
10
9, not detected
Scheme 3.
PKR has been documented.19 The use of anhydrous
acetonitrile had a deleterious effect on the efficiency of
the reaction.20
To explore the generality of this new reaction, a variety
of substrates with substituents offering different elec-
tronic and steric properties at the alkynyl and propar-
gylic positions were examined.21 The results of these
studies are presented in Table 1. Entry 1 showed that
terminal alkynes participate in the reaction, although
this substrate required 24 h for consumption of starting
material. In entries 2 and 3, enynes without substitution
at the propargylic position were shown to undergo
analogous cyclization. In entries 4 and 5, enynes with a
doubly activated benzylic and propargylic ether each
provided enone 18 in moderate yield. Throughout these
investigations, and illustrated specifically with entries 4
and 5, both the dimethyl and diphenyl silyl tethers
behaved similarly. The reaction of the pivaldehyde eny-
nes 20 and 22 were anomalous in that no reduction at
the propargylic position occurred in these substrates.
The diphenyl silanol group in product 23 helped secure
crystals (mp 95–98°C, hexanes) suitable for X-ray anal-
ysis (Fig. 1).22 Bicyclic enones (e.g. 3) were not observed
in any of the reactions reported in Table 1.
The enone products in Table 1 are formally the result
of an intermolecular PKR with an alkyne and ethylene
gas.23,24 For most laboratory preparations this new
method is superior to the reaction with ethylene for
several reasons. Specifically, the reaction does not
require high pressures or special equipment, and the
propargylic oxygen ensures that only one of the two
possible isomeric enones is formed during the reaction.
In summary, we have reported the first Pauson–Khand
reactions of silicon-tethered enynes in which the car-
Figure 1. ORTEP representation of 23.

J. F. Reichwein et al. / Tetrahedron Letters 43 (2002) 3739–3741
3741
the reaction mechanism and full experimental details
will be reported elsewhere.20
R.; Takahashi, T. Tetrahedron Lett. 1987, 28, 917–920.
Pagenkopf, B. L.; Lund, E. C.; Livinghouse, T. Tetra-
hedron 1995, 51, 4421–4438.
11. Simonian, S. O.; Smit, W. A.; Gybin, A. S.; Shashkov, A.
S.; Mikaelian, G. S.; Tarasov, V. A.; Ibragimov, I. I.;
Caple, R.; Froen, D. E. Tetrahedron Lett. 1986, 27,
1245–1248.
12. (a) Shambayati, S.; Crowe, W. E.; Schreiber, S. L. Tetra-
hedron Lett. 1990, 31, 5289–5292; (b) Jeong, N.; Chung, Y.
K.; Lee, B. Y.; Lee, S. H.; Yoo, S. E. Synlett 1991, 204–206.
13. Chung, Y. K.; Lee, B. Y.; Jeong, N.; Hudecek, M.; Pauson,
P. L. Organometallics 1993, 12, 220–223.
Acknowledgements
We thank the Robert A. Welch Foundation for finan-
cial support and Vincent Lynch for determination of
the X-ray structure. M.C.P. thanks the University of
Texas at Austin for an undergraduate research
fellowship.
14. Sugihara, T.; Yamada, M.; Ban, H.; Yamaguchi, M.;
Kaneko, C. Angew. Chem., Int. Ed. Engl. 1997, 36, 2801–
2804.
References
15. Perez-Serrano, L.; Blanco-Urgoiti, J.; Casarrubios, L.;
Dominguez, G.; Perez-Castells, J. J. Org. Chem. 2000, 65,
3513–3519.
1. Liu, T.; Stern, A.; Roberts, L. J.; Morrow, J. D. J. Biomed.
Sci. 1999, 6, 226–235.
2. (a) Gauthier, D. R.; Zandi, K. S.; Shea, K. J. Tetrahedron
1998, 54, 2289–2338; (b) Fensterbank, L.; Malacria, M.;
Sieburth, S. M. Synthesis 1997, 813–854; (c) Bols, M.;
Skrydstrup, T. Chem. Rev. 1995, 95, 1253–1277.
3. (a) Schore, N. E. Org. React. 1991, 40, 1–90; (b) Shore, N.
E. In Comprehensive Organometallic Chemistry II; Hege-
dus, L. S., Ed.; Elsevier: Oxford, 1995; Vol. 12, p. 703; (c)
Ingate, S. T.; Marco-Contelles, J. Org. Prep. Proced. Int.
1998, 30, 121–143; (d) Geis, O.; Schmalz, H.-G. Angew.
Chem., Int. Ed. 1998, 37, 911–914; (e) Chung, Y. K. Coord.
Chem. Rev. 1999, 188, 297–341; (f) Brummond, K. M.;
Kent, J. L. Tetrahedron 2000, 56, 3263–3283; (g) Fletcher,
A. J.; Christie, S. D. R. J. Chem. Soc., Perkin. Trans. 1
2000, 1657–1668; (h) Sugihara, T.; Yamaguchi, M.;
Nishizawa, M. Chem. Eur. J. 2001, 7, 1589–1595.
4. Kagoshima, H.; Hayashi, M.; Hashimoto, Y.; Saigo, K.
Organometallics 1996, 15, 5439–5441.
16. Sugihara, T.; Yamada, M.; Yamaguchi, M.; Nishizawa, M.
Synlett 1999, 771–773.
1
17. All products were fully characterized by IR, H and 13C
NMR and HRMS.
18. Representative procedure: 2-propyl-3-phenylpropyl-2-cyl-
copenten-1-one (10). To a solution of Co2(CO)8 (342 mg,
1.00 mmol) in MeCN (4 mL, containing 1% H2O) under
an atmosphere of nitrogen was added enyne 8 (287 mg, 1.00
mmol) in MeCN (1 mL). After stirring for 1 h at rt, the
reaction flask was placed into a preheated oil bath (135°C)
to bring the reaction mixture quickly to reflux. After 30 min
the reaction flask was removed from the oil bath and
allowed to cool to rt. The volatile components were
removed in vacuo, and the residue was purified by flash
chromatography on silica gel using 40% EtOAc/hexanes
for elution to afford the title compound 10 as a pale yellow
oil (149 mg, 62%). Rf 0.65 (40% EtOAc/hexanes); IR (thin
5. Jones, T. K.; Denmark, S. E. Helv. Chim. Acta 1983, 66,
2377–2396.
6. Probert, G. D.; Harding, R.; Whitby, R. J.; Coote, S. J.
Synlett 1997, 1371–1374.
1
film) w 3447 (br, m), 2930 (m), 1706 (s), 1614 (s) cm−1; H
NMR (300 MHz, CDCl3) l 7.34–7.19 (m, 5H), 2.69 (t,
J=7.8 Hz, 2H), 2.50–2.45 (m, 4H), 2.39–2.36 (m, 2H), 2.13
(t, J=7.5 Hz, 2H), 1.91–1.85 (m, 2H), 1.43–1.36 (m, 2H),
0.88 (t, J=7.5, 3H); 13C NMR (75 MHz, CDCl3) l 210.3
(C), 173.7 (C), 141.7 (C), 140.8 (C), 128.7 (CH), 128.6
(CH), 126.3 (CH), 36.1 (CH2), 34.5 (CH2), 31.0 (CH2), 29.4
(CH2), 29.2 (CH2), 25.4 (CH2), 22.1 (CH2), 14.4 (CH3);
HRMS m/z calcd for C17H23O [M+H]+ 243.1749, found
243.1741.
7. Jeong, N.; Hwang, S. H.; Lee, Y. S.; Chung, Y. K. J. Am.
Chem. Soc. 1994, 116, 3159–3160.
8. (a) Pagenkopf, B. L.; Livinghouse, T. J. Am. Chem. Soc.
1996, 118, 2285–2286; (b) Belanger, D. B.; O’Mahony, D.
J. R.; Livinghouse, T. Tetrahedron Lett. 1998, 39, 7637–
7640; (c) Belanger, D. B.; Livinghouse, T. Tetrahedron
Lett. 1998, 39, 7641–7644; (d) Pagenkopf, B. L.; Belanger,
D. B.; O’Mahony, D. J. R.; Livinghouse, T. Synthesis 2000,
1009–1019.
19. Hoye, T. R.; Suriano, J. A. J. Org. Chem. 1993, 58,
1659–1660.
20. Reichwein, J. F.; Iacono, S. T.; Pagenkopf, B. L. Tetra-
9. Krafft, M. E.; Bonaga, L. V. R.; Hirosawa, C. J. Org.
Chem. 2001, 66, 3004–3020.
hedron 2002, in press.
21. For a ‘reductive Pauson–Khand’ variant, see: Krafft, M.
E.; Bonaga, L. V. R.; Wright, J. A.; Hirosawa, C. J. Org.
Chem. 2002, 67, 1233–1246.
10. Other metal catalysts explored with these silicon tethered
enynes included [Ir(COD)Cl]2·2(S)-tolBINAP: Shibata, T.;
Takagi, K. J. Am. Chem. Soc. 2000, 122, 9852–9853;
Mo(CO)6: Jeong, N.; Lee, S. J. Tetrahedron Lett. 1993, 34,
4027–4030; [RhCl(CO)dppp]2: Jeong, N. Organometallics
1998, 17, 3642–3644; Evans, P. A.; Robinson, J. E. J. Am.
Chem. Soc. 2001, 123, 4609–4610; Ru3(CO)12: Kondo, T.;
Nobuyoshi, S.; Okada, T.; Mitsudo, T. J. Am. Chem. Soc.
1997, 119, 6187–6188; Morimoto, T.; Chatani, N.; Fuku-
moto, Y.; Murai, S. J. Org. Chem. 1997, 62, 3762–3765;
‘Cp2Ti’: Hicks, F. A.; Berk, S. C.; Buchwald, S. L. J. Org.
Chem. 1996, 61, 2713–2718; ‘Cp2Zr’: Negishi, E.; Ceder-
baum, F. R.; Takahashi, T. Tetrahedron Lett. 1986, 27,
2829–2832. Negishi, E.; Swanson, D. R.; Cederbaum, F.
22. Crystallographic data for structure 23 has been deposited
with the Cambridge Crystallographic Data Center as
supplementary publication number CCDC 175779. Copies
of the data can be obtained, free of charge, on application
to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax:
+44(0)-1223-336033 or email: deposit@ccdc.cam.ac.uk].
23. Khand, I. U.; Pauson, P. L. J. Chem. Res. (M) 1977,
168–177.
24. (a) Kerr, W. J.; McLaughlin, M.; Pauson, P. L.; Robertson,
S. M. Chem. Commun. 1999, 2171–2172; (b) Kerr, W. J.;
McLaughlin, M.; Pauson, P. L.; Robertson, S. M. J.
Organomet. Chem. 2001, 630, 104–117.