Pauson-Khand cycloaddition reactions of chiral ynamides. Observation of an unusual endo-addition with norbornadiene

Article abstract of DOI:10.1016/j.tetlet.2003.10.064

Pauson-Khand cycloadditions using chiral ynamides are achieved in modest to good yields with excellent regioselectivity and modest stereoselectivity. An unusual endo addition is found when using norbornadiene and substituted ynamides, leading to cycloaddu

Full text of DOI:10.1016/j.tetlet.2003.10.064

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 9353–9358
Pauson–Khand cycloaddition reactions of chiral ynamides.
Observation of an unusual endo-addition with norbornadiene
Lichun Shen and Richard P. Hsung*,†
Department of Chemistry, University of Minnesota, Minneapolis, MN 55455, USA
Received 26 September 2003; accepted 7 October 2003
Abstract—Pauson–Khand cycloadditions using chiral ynamides are achieved in modest to good yields with excellent regioselectiv-
ity and modest stereoselectivity. An unusual endo addition is found when using norbornadiene and substituted ynamides, leading
to cycloadducts that were not observed in previous studies using ynamides or ynamines.
© 2003 Elsevier Ltd. All rights reserved.
Ynamides are becoming synthetically useful synthons
especially for use in transition metal-mediated pro-
cesses.1–4 The distinct stability of ynamides 1–3 (Fig. 1)
over traditional ynamines5 renders them viable sub-
strates for developing stereoselective6,7 and intramolec-
ular reactions8 that are otherwise challenging with
ynamines. Our efforts in this area4 and recent success in
achieving a facile synthesis of chiral ynamides 3 via
Cu-catalyzed cross-coupling3 led us to examine the
possibility of achieving auxiliary-driven asymmetric
Pauson–Khand cycloadditions.9–13 Co- or Fe-mediated
Pauson–Khand cycloadditions using ynamides have
been elegantly described recently by Rainier,10 Witul-
ski,11 and Chen.12 Specifically, Witulski11 reported
stereoselective intramolecular Pauson–Khand cycload-
ditions using tethered chiral sulfonyl-substituted
ynamides 1. However, Pauson–Khand reactions using
chiral auxiliary-based ynamides such as 3 have not been
explored.7a,14 We report here our findings related to
regio- and stereoselectivity issues in Pauson–Khand
cycloadditions of chiral ynamides as well as an unusual
endo-addition with norbornadiene.
To explore the feasibility ynamide Pauson–Khand
cycloaddition, chiral ynamides 6 and 7 were treated
with 1.05 equiv. of Co2(CO)8 at rt in CH2Cl2, providing
the respective cobalt carbonyl complexes 8 and 915 as
deep purple solids in 40–50% yield (Scheme 1). All
Figure 1.
* Corresponding author. E-mail: hsung@chem.umn.edu
† A recipient of 2001 Camille Dreyfus Teacher–Scholar Award.
Scheme 1.
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.10.064

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L. Shen, R. P. Hsung / Tetrahedron Letters 44 (2003) 9353–9358
attempts to secure an X-ray structure of these com-
plexes failed. Subsequent Pauson–Khand reactions of 8
and 9 with norbornadiene (NBD) were carried out in
various solvents in the presence of 6.0 equiv. Me3NO.
In each case, a mixture of three isomers (10–11a,b from
8, and 12–13a,b from 9) was isolated in 35–50% yield.
analysis that also distinctly revealed the same
anisotropic effect of the Ph ring observed in H NMR.
1
Pauson–Khand reactions of synthetically useful chiral
ynamides are shown in Scheme 3. Ynamides 19 and 20
were prepared from alkynyl bromides 17 and 18,
respectively, in good yields using Cu-catalyzed cross-
coupling.3a Subsequent cycloadditions of 19 and 20
afforded separable mixtures of endo (21 and 23, respec-
tively) and exo (22a,b and 24a,b, respectively) isomers
in modest overall yields19 with the endo addition again
being stereoselective.
The expected exo products 11a,b and 13a,b exhibited
excellent regioselectivity with only 2-amido enones (see
regioisomer 4 in Fig. 1) being present as shown by
NOE, although there is no diastereoselectivity. More
interestingly, not only were we quite surprised with the
finding of endo products 10 and 12, but these endo
products were also isolated as single regio- and
stereoisomers. This result represents an unusual sce-
nario in Pauson–Khand cycloadditions using NBD
since exo products are formed almost exclusively.7a,9,11
The related endo products were also not found in the
work of Perica`s7a,14 and Witulski11 using ynamines and
ynamides, respectively. However, it should be noted
that Livinghouse16a and Carretero16b,c did report
unusual endo-selective intramolecular Pauson–Khand
cycloadditions. In addition, Perica`s17 recently isolated
endo products from Pauson–Khand cycloadditions of
NBD with hetero bimetallic (MoꢀCo) complexes of
N-(2-alkynoyl)oxazolidinones or sultams, although
exo-selectivity remained in reactions using dicobalt
complexes of the same substrates.16
We briefly examined other chiral auxiliaries as shown in
products 25 and 26, and endo isomers were again
observed,20 although it was non-stereoselective, leading
to all four possible isomers. In addition, the reaction of
6 with norbornene led to 27 also as a mixture of four
isomers. By comparing with reactions of ynamides 6, 7,
14, 19–20 with NBD, these latter results imply that the
Ph group on the oxazolidinone auxiliary and the usage
of NBD are important in providing the selectivity for
the endo addition.
To improve the efficiency of this cycloaddition, we
examined two variables as shown in Scheme 4. Initially,
we were concerned there was an insufficient amount of
CO to render Co-insertion effective, but the reaction of
ynamide 6 with NBD under a blanket of 1 atm of CO
led to 10 in 9% yield. Also, both Perica`s7a and
Witulski11 had employed terminal unsubstituted
ynamines or ynamides and indicated that substituted
ynamines or ynamides gave lower yields; however, the
opposite was true in our work. However, reactions of
ynamide 28 with NBD and norbornene led to cycload-
ducts 29 and 30 in only 16 and 17% yield,
respectively.21
These endo-addition products were assigned initially
based on NOE and the fact that the unusual shifting of
olefinic protons Ha and Hb (see 10 and 12 in Scheme 1)
toward upfield could only be explained by the close
proximity of the phenyl ring on the Evans’ oxazolidi-
none auxiliary.18 However, the reaction of ynamide 14
with NBD allowed isolation of the crystalline endo-
product 15 as a single diastereomer with an overall
yield of 30% (Scheme 2).19 The endo stereochemistry
was unambiguously assigned using single crystal X-ray
Scheme 3.
Scheme 2.

L. Shen, R. P. Hsung / Tetrahedron Letters 44 (2003) 9353–9358
9355
Scheme 6.
Scheme 4.
While we are further exploring optimization issues, it
has become quite intriguing mechanistically especially
since we now only observe exo products when using
unsubstituted ynamides.7a,11,22 To rationalize these
results, a mechanistic working model is illustrated in
Schemes 5–7.
Scheme 7.
Presently, we are uncertain as to why the endo-coordi-
nated complex-II 33b would be favored over 33b to
undergo MI, while the corresponding exo-coordinated
complexes (not shown) do not appear to have any
preferences. Unfortunately, preliminary low-level
(PM3) calculations were inconclusive. By comparing
stabilities of migratory-inserted intermediates,7a one
postulation would be that the migratory-inserted endo-
intermediate-II 34b (a different perspective shown in
Scheme 6) is favored over endo-intermediate-I 34a
because of the orbital overlap or p-stacking between the
Ph ring of the auxiliary and the second olefin of NBD
seen in the modeling of 34b (see the arrow). This
p-stacking is absent in the endo-intermediate-I 34a as
well as in both exo-intermediates 37a and 37b.
Based on related transition metal carbonyl complexes
containing Evans’ type auxiliary,23 it may be proposed
that cobalt complexes 31 and 32 can have the carbonyl
group of oxazolidinone coordinated to either
diastereotopic (Pro-R or S before coordination) Co
metal with 32 being favored for having less steric
congestion (Scheme 5). Loss of a CO ligand in 32
would allow coordination of NBD at its endo (or exo,
not shown) face to either the R- or S-Co metal. This
would lead to two diastereomeric endo-coordinated
complexes 33a and 33b with the favored product 36b
(endo-II) being derived from 33b through migratory
insertion (MI) and CO-insertion intermediates 34b and
35b.
In addition, support for this stacking could be found in
1
both the X-ray structure of 15 and in the H NMR of
cycloadducts 10, 12, 21, and 23 in which both olefinic
protons (Ha and Hb) are unusually upfield shifted,
suggesting an anisotropic effect of the phenyl ring. This
observation is also in good agreement with results from
using other ynamides that lack this particular phenyl
ring (see 25), or norbornene that lacks this extra double
bond (see 27), the selectivity for endo products is lost,
leading to both endo-I and -II products.
A second factor would be the observation of the endo
addition product only when using substituted
ynamides. To address this issue, our molecular model-
ing reveals that although being less congested, coordi-
nation at the exo face of NBD or norbornene would
lead to the unwanted steric interaction with the R
group as shown in 38 (Scheme 7). Thus, when R=H,
we as well as others7a,11 have observed only the exo
addition. On the other hand, despite being more con-
gested, coordination at the endo face of NBD (or
norbornene, see 39) would be devoid of such steric
interaction, and in the case of NBD, it could also
benefit from a double coordination with both Co
metals (see 40).
Scheme 5.

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L. Shen, R. P. Hsung / Tetrahedron Letters 44 (2003) 9353–9358
We have described here Pauson–Khand cycloaddition
reactions of chiral ynamides. These reactions can be
achieved in excellent regioselectivity, although in mod-
est stereoselectivity. When norbornadiene and substi-
tuted ynamides were used, an unusual endo addition
occurred leading to cycloadducts that were not
observed in previous studies using ynamines or
ynamides. Efforts are underway to further investigate
the mechanism and to develop applications of this
cycloaddition.
5. For reviews on chemistry of ynamines, see: (a) Himbert,
G. In Methoden Der Organischen Chemie (Houben-Weyl);
Kropf, H.; Schaumann, E., Eds.; Georg Thieme Verlag:
Stuttgart, 1993; pp. 3267–3443; (b) Collard-Motte, J.;
Janousek, Z. Top. Curr. Chem. 1986, 130, 89; (c) Ficini, J.
Tetrahedron 1976, 32, 1448.
6. For the only account using chiral ynamines before 1997,
see: (a) van Elburg, P. A.; Honig, G. W. N.; Reinhoudt,
D. N. Tetrahedron Lett. 1987, 28, 6397; (b) For a recent
account using ynamines to prepare optically enriched
g-butanolides, see: (b) Movassaghi, M.; Jasobsen, E. N.
J. Am. Chem. Soc. 2002, 124, 2456.
7. For the recent two accounts of chemistry of chiral
ynamines, see: (a) Balsells, J.; Va´zquez, J.; Moyano, A.;
Perica`s, M. A.; Riera, A. J. Org. Chem. 2000, 65, 7291;
(b) Roth, G.; Reindl, D.; Gockel, M.; Troll, C.; Fischer,
H. Organometallics. 1998, 17, 1393; (c) Fischer, H.; Pod-
schadly, O.; Roth, G.; Herminghaus, S.; Klewitz, S.;
Heck, J.; Houbrechts, S.; Meyer, T. J. Organomet. Chem.
1997, 541, 321.
Acknowledgements
The authors would like to thank the NSF (CHE-
0094005) for support. They would also like to thank
Dr. Victor Young for providing X-ray structural analy-
sis and Professor Kay Brummond for valuable
discussions.
8. For the only intramolecular reaction using ynamine, see:
Genet, J. P.; Kahn, P.; Ficini, J. Tetrahedron Lett. 1980,
21, 1521.
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J. A.; Hsung, R. P.; Rameshkumar, C.; Wei, L.-L. Tetra-
hedron 2001, 57, 7575; (b) Mulder, J. A.; Kurtz, K. C.
M.; Hsung, R. P. Synlett 2003, 1379. For the first prepa-
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ynamides, see: (a) Witulski, B.; Alayrac, C.; Tevzaadze-
Saeftel, L. Angew. Chem., Int. Ed. 2003, 42, 4257; (b)
Tanaka, R.; Hirano, S.; Urabe, H.; Sato, F. Org. Lett.
2003, 5, 67; (c) Witulski, B.; Lumtscher, J.; Bergstra¨ßer,
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Mori, M. Org. Lett. 2002, 4, 803; (g) Timbert, J.-C.;
Cintrat, J.-C. Chem. Eur. J. 2002, 8, 1637; (h) Minie`re, S.;
Cintrat, J.-C. Synthesis 2001, 705; (i) Minie`re, S.; Cintrat,
J.-C. J. Org. Chem. 2001, 66, 7385; (j) Hoffmann, R. W.;
Bru¨ckner, D. New. J. Chem. 2001, 25, 369; (k) For
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3. For our syntheses of ynamides, see: (a) Frederick, M. O.;
Mulder, J. A.; Tracey, M. R.; Hsung, R. P.; Huang, J.;
Kurtz, K. C. M.; Shen, L.; Douglas, C. J. J. Am. Chem.
Soc. 2003, 125, 2368; (b) For a related account, see:
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14. For an example of using chiral ynol ether in Pauson–
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1994, 116, 2153.

L. Shen, R. P. Hsung / Tetrahedron Letters 44 (2003) 9353–9358
9357
15. General procedure for the Pauson–Khand reaction of
ynamides: To a solution of an appropriate ynamide (0.2
mmol) in CH2Cl2 (2 mL) was added Co2(CO)8 (72.8 mg,
0.21 mmol). The mixture was stirred at rt for 30 min until
the complex was formed completely as indicated by TLC.
The respective alkene (2.0 mmol) was then added to the
reaction mixture, and after cooling to −10°C, a solution
of TMANO (1.2 mmol) in CH2Cl2 (1 ml) was added to
dropwise. The reaction was warmed to rt and allowed to
react for 10–16 h. Once completed, the reaction mixture
was filtered through a small bed of celite and concen-
trated under reduced pressure. Purification of the crude
material using silica gel column chromatography (gradi-
ent eluent: 10% to 50% EtOAc in hexanes) afforded the
respective cycloadduct.
45.19, 49.22, 51.58, 59.45, 70.25, 127.80, 128.46, 128.86,
131.47, 132.56, 134.54, 137.17, 155.57, 176.73, 204.11; IR
(thin film) cm−1 2958 (m), 1762 (s), 1699 (s), 1406 (m),
1210 (m), 702 (m); LC–MS: m/e (% relative intensity) 364
(100) (M+H+), 298 (10).
15: Rf=0.37 (50% EtOAc in hexanes); [h]2D3=+42.3° (c
0.53, CH2Cl2); 1H NMR (500 MHz, CDCl3) l 1.58 (d,
1H, J=8.5 Hz), 1.66 (dt, 1H, J=8.5, 2.0 Hz), 2.91 (t, 1H,
J=5.5 Hz), 2.96 (brd, 1H), 3.18 (brd, 1H), 3.61 (dd 1 H,
J=4.0, 5.5 Hz), 4.23 (t, 1H, J=9.0 Hz), 4.67 (t, 1H,
J=8.5 Hz), 5.03 (dd, 1H, J=3.0, 5.5 Hz), 5.47 (t, 1H,
J=9.0 Hz), 5.56 (dd, 1H, J=3.0, 5.5 Hz), 7.06–7.08 (m,
2H), 7.20–7.28 (m, 2H), 7.39–7.46 (m, 6H); 13C NMR
(125 MHz, CDCl3) l 31.60, 44.68, 46.47, 49.37, 51.70,
126.09, 126.45, 127.78, 127.91, 128.14, 128.33, 128.47,
128.63, 130.40, 133.24, 133.97, 136.20, 156.09, 204.09; IR
(thin film) cm−1 2925 (m), 1761 (s), 1700 (s), 1395 (m),
1209 (m); LC–MS: m/e (% relative intensity) 384 (100)
(M+H+), 318 (10).
Characterization of selected new compounds: 10: Rf=0.18
(33% EtOAc in hexanes); [h]2D3=−80.8° (c 0.34, CH2Cl2);
1H NMR (500 MHz, CDCl3) l 0.92 (t, 3H, J=7.0 Hz),
1.25–1.42 (m, 6H), 1.49 (d, 1H, J=8.0 Hz), 1.63 (d, 1H,
J=8.0 Hz), 1.83–1.89 (m, 1H), 2.40–2.46 (m, 1H), 2.76 (t,
1H, J=5.0 Hz), 2.83 (brd, 1H), 3.03 (brd, 1H), 3.25 (t,
1H, J=5.0 Hz), 4.24 (t, 1H, J=9.0 Hz), 4.73 (t, 1H,
J=9.0 Hz), 4.85 (dd, 1H, J=3.0, 6.0 Hz), 5.17 (dd, 1H,
J=3.0, 6.0 Hz), 5.62 (t, 1H, J=9.0 Hz), 7.23–7.25 (m,
2H), 7.32–7.36 (m, 3H); 13C NMR (75 MHz, CDCl3) l
13.96, 22.43, 26.51, 29.80, 30.32, 31.44, 43.63, 43.89,
45.26, 49.28, 51.63, 59.45, 70.31, 127.83, 128.50, 128.90,
131.47, 132.64, 134.52, 137.24, 155.60, 176.77, 204.20; IR
(thin film) cm−1 2928 (m), 2857 (m), 1762 (s), 1700 (s),
1405 (m), 1212 (m); LC–MS: m/e (% relative intensity)
392 (100) (M+H+), 326 (18).
21: Rf=0.63 (50% EtOAc in hexanes); [h]2D3=−58.57° (c
0.40, CH2Cl2); 1H NMR (500 MHz, CDCl3) l 0.08 (s,
6H), 0.90 (s, 9H), 1.46 (d, 1H, J=7.5 Hz), 1.58 (dt, 1H,
J=7.5, 1.5 Hz), 2.08–2.11 (m, 1H), 2.65–2.68 (m, 1H),
2.74 (t, 1H, J=5.0 Hz), 2.90 (brd, 1H), 3.01 (brd, 1H),
3.40 (t, 1H, J=5.0 Hz), 3.86–3.92 ( m, 2H), 4.22 (t, 1H,
J=9.5 Hz), 4.73 (t, 1H, J=9.0 Hz), 4.86 (dd, 1H, J=3.0,
6.0 Hz), 5.07 (dd, 1H, J=3.0, 6.0 Hz), 5.68 (t, 1H, J=9.5
Hz), 7.22–7.26 (m, 2H), 7.33–7.36 (m, 3H); 13C NMR (75
MHz, CDCl3) l −5.50, 18.12, 25.78, 33.50, 43.63, 44.07,
46.37, 49.35, 51.53, 59.25, 60.44, 70.41, 127.78, 128.57,
128.96, 131.57, 132.42, 135.15, 137.13, 174.06, 204.27
(missing 1 signal due to overlap); IR (thin film) cm−1 2952
(m), 2854 (m), 1762 (s), 1700 (s), 1401 (m), 1251 (m);
LC–MS: m/e (% relative intensity) 466 (100) (M+H+), 334
(30).
11a: Rf=0.44 (50% EtOAc in hexanes); [h]2D3=−138.6° (c
0.49, CH2Cl2); 1H NMR (500 MHz, CDCl3) l 0.90 (t,
1H, J=7.0 Hz), 1.05–1.07 (m, 1H), 1.16–1.29 (m, 8H),
1.42–1.46 (m, 1H), 2.09 (d, 1H, J=5.0 Hz), 2.31–2.36 (m,
1H), 2.47–2.53 (m, 1H), 2.57 (d, 1H, J=5.0 Hz), 2.76
(brd, 1H), 2.88 (brd, 1H), 4.31 (t 1 H, J=7.0 Hz), 4.77 (t,
1H, J=8.5 Hz), 5.71 (t, 1H, J=8.0 Hz), 6.17 (dd, 1H,
J=3.0, 6.0 Hz), 6.23 (dd, 1H, J=3.0, 5.5 Hz), 7.30–7.38
(m, 5H); IR (thin film) cm−1 2928 (m), 2854 (m), 1767 (s),
1634 (s), 1401 (m), 1200 (m); LC–MS: m/e (% relative
intensity) 392 (100) (M+H+).
1
22a,b: Rf=0.68 (50% EtOAc in hexanes); H NMR (500
MHz, CDCl3) 22a: l 0.01–0.03 (m, 7H), 0.84–0.87 (m,
10H), 2.08 (d, 1H, J=4.5 Hz), 2.73 (d, 1H, J=5.0 Hz),
2.74–2.79 (m, 1H), 2.83 (brd, 1H), 2.87 (brd, 1H), 3.38–
3.42 (m, 1H), 3.86–3.95 (m, 2H), 4.28 (t 1 H, J=8.5 Hz),
4.77 (t, 1H, J=9.0 Hz), 5.76 (t, 1H, J=8.5 Hz), 6.16 (dd,
1H, J=3.0, 6.0 Hz), 6.22 (dd, 1H, J=2.5, 5.0 Hz),
7.29–7.36 (m, 5H); 22b: l 0.05–0.08 (m, 7H), 0.91–0.93
(m, 10H), 2.18 (d, 1H, J=5.5 Hz), 2.28–2.34 (m, 1H),
2.54–2.60 (m, 1H), 2.61 (brd, 1H), 2.66 (brd, 1H), 2.85 (d,
1H, J=5.0 Hz), 3.66–3.70 (m, 2H), 4.31 (t 1 H, J=8.5
Hz), 4.78 (t, 1H, J=9.0 Hz), 5.80 (t, 1H, J=8.5 Hz), 6.13
(dd, 1H, J=3.0, 5.5 Hz), 6.16 (dd, 1H, J=3.0, 6.0 Hz),
7.29–7.36 (m, 5H); LC–MS: m/e (% relative intensity) 466
(100) (M+H+).
23: Rf=0.47 (50% EtOAc in hexanes); mp 94–96°C;
[h]2D3=−54.89° (c 0.63, CH2Cl2); 1H NMR (500 MHz,
CDCl3) l 0.07 (s, 6H), 0.90 (s, 9H), 0.48 (d, 1H, J=9.0
Hz), 1.51–1.56 (m, 2H), 1.60 (dt, 1H, J=9.0, 2.0 Hz),
1.64–1.70 (m, 2H), 1.88–1.94 (m, 1H), 2.42–2.48 (m, 1H),
2.75 (t, 1H, J=5.0 Hz), 2.83 (brd, 1H), 3.03 (brd, 1H),
3.25 (t, 1H, J=5.0 Hz), 3.63–3.66 ( m, 2H), 4.23 (t, 1H,
J=8.5 Hz), 4.72 (t, 1H, J=9.0 Hz), 4.84 (dd, 1H, J=3.0,
6.0 Hz), 5.16 (dd, 1H, J=3.0, 6.0 Hz), 5.61 (t, 1H, J=9.0
Hz), 7.22–7.24 (m, 2H), 7.34–7.35 (m, 3H); 13C NMR (75
MHz, CDCl3) l −5.38, 18.21, 22.93, 25.84, 30.02, 32.97,
43.65, 43.91, 45.21, 49.30, 51.67, 59.45, 62.50, 70.36,
127.84, 128.54, 128.93, 131.47, 132.66, 134.67, 137.22,
11b: Rf=0.38 (50% EtOAc in hexanes); [h]2D3=−148.5° (c
0.51, CH2Cl2); 1H NMR (500 MHz, CDCl3) l 0.14 (d,
1H, J=9.0 Hz), 0.90 (t, 1H, J=7.0 Hz), 1.23–1.34 (m,
8H), 2.05–2.09 (m, 1H), 2.19 (d, 1H, J=5.0 Hz), 2.47–
2.53 (m, 1H), 2.50 (brd, 1H), 2.67 (d, 1H, J=5.0 Hz), 70
(brd, 1H), 4.33 (t 1 H, J=9.0 Hz), 4.78 (t, 1H, J=8.5
Hz), 5.75 (t, 1H, J=8.0 Hz), 6.14 (dd, 1H, J=2.5, 5.0
Hz), 6.18 (dd, 1H, J=2.5, 5.0 Hz), 7.30–7.35 (m, 5H); IR
(thin film) cm−1 2930 (m), 2859 (m), 1766 (s), 1703 (s),
1403 (m); LC–MS: m/e (% relative intensity) 392 (100)
(M+H+).
12: Rf=0.57 (50% EtOAc in hexanes); [h]2D3=−127.74° (c
0.58, CH2Cl2); 1H NMR (300 MHz, CDCl3) l 0.89 (t,
3H, J=6.9 Hz), 1.31–1.38 (m, 4H), 1.42 (d, 1H, J=8.4
Hz), 1.54 (d, 1H, J=8.4 Hz), 1.75–1.86 (m, 1H), 2.32–
2.43 (m, 1H), 2.69 (t, 1H, J=5.4 Hz), 2.78 (brd, 1H), 2.96
(brd, 1H), 3.19 (t, 1H, J=5.4 Hz), 4.17 (t, 1H, J=8.7
Hz), 4.65 (t, 1H, J=8.7 Hz), 4.79 (dd, 1H, J=2.7, 5.4
Hz), 5.12 (dd, 1H, J=2.7, 5.4 Hz), 5.53 (t, 1H, J=8.7
Hz), 7.21–7.25 (m, 2H), 7.30–7.35 (m, 3H); 13C NMR (75
MHz, CDCl3) l 13.72, 22.81, 28.56, 29.95, 43.57, 43.86,

9358
L. Shen, R. P. Hsung / Tetrahedron Letters 44 (2003) 9353–9358
176.57, 204.26 (missing 1 signal due to overlap); IR (thin
2.61–2.64 (m, 1H), 4.31 (dd, 1H, J=4.2, 8.7 Hz), 4.76 (t,
1H, J=8.7 Hz), 6.03 (dd, 1H, J=3.9, 9.0 Hz), 7.20–7.23
(m, 2H), 7.29–7.37 (m, 3H), 7.63 (d, 1H, J=3.0 Hz); IR
(thin film) cm−1 2953 (m), 2872 (m), 1754 (s), 1700 (s),
1399 (s); GC–MS: m/e (% relative intensity) 309 (3)
(M+H+), 265 (100), 198 (54).
film) cm−1 2932 (m), 2858 (m), 1764 (s), 1702 (s), 1406
(m); LC–MS: m/e (% relative intensity) 494 (100) (M+
H+).
1
29a,b: Rf=0.43 (25% EtOAc in hexanes); H NMR (300
MHz, CDCl3) 29a: l 1.25 (d, 1H, J=9.6 Hz), 1.35 (d,
1H, J=9.6 Hz), 2.03–2.05 (m, 1H), 2.62–2.64 (m, 1H),
2.76 (brd, 1H), 2.86 (brd, 1H), 4.23 (dd, 1H, J=4.2, 8.7
Hz), 4.72 (t, 1H, J=8.7 Hz), 6.04 (dd, 1H, J=3.9, 9.0
Hz), 6.13 (dd, 1H, J=3.0, 5.4 Hz), 6.26 (dd, 1H, J=3.0,
5.4 Hz), 7.21–7.24 (m, 2H), 7.30–7.34 (m, 3H), 7.80 (d,
1H, J=3.3 Hz); 29b: l 0.27 (d, 1H, J=9.6 Hz), 0.95–0.97
(m, 1H), 2.15–2.17 (m, 1H), 2.50 (brd, 1H), 2.55 (brd,
1H), 2.62–2.65 (m, 1H), 2.71–2.73 (m, 1H), 4.30 (dd, 1H,
J=4.2, 8.7 Hz), 4.75 (t, 1H, J=8.7 Hz), 6.01 (dd, 1H,
J=3.6, 8.4 Hz), 6.10 (dd, 1H, J=3.0, 5.4 Hz), 6.22 (dd,
1H, J=3.0, 5.4 Hz), 7.21–7.24 (m, 2H), 7.30–7.34 (m,
3H), 7.70 (d, 1H, J=3.0 Hz); IR (thin film) cm−1 2975
(m), 1762 (s), 1703 (s), 1400 (s); GC–MS: m/e (% relative
intensity) 307 (100) (M+H+), 241 (54), 196 (72).
16. (a) Pagenkopf, B. L.; Belanger, D. B.; O’Mahony, D. J.
R.; Livinghouse, T. Synthesis 2000, 1009. Also see: (b)
Adrio, J.; Rivero, M. R.; Carretero, J. C. Chem. Eur. J.
2001, 7, 2435; (c) Adrio, J.; Rivero, M. R.; Carretero, J.
C. Angew. Chem., Int. Ed. 2000, 39, 2906.
17. Rios, R.; Perica`s, M. A.; Moyano, A.; Maestro, M. A.;
Mah´ıa, J. Org. Lett. 2002, 4, 1205.
18. (a) Evans, D. A. Aldrichim. Acta 1982, 15, 23; (b) Heath-
cock, C. H. Aldrichim. Acta 1990, 23, 99.
19. Despite being modest, the overall yield implies the
cycloaddition step occurred in about 60% since our best
yield for the formation of the cobalt complex is around
50%. This is the case with later examples as well.
20. The endo/exo stereochemistry in 26 was not vigorously
assigned.
1
30a,b: Rf=0.38 (33% EtOAc in hexanes); H NMR (300
21. We did use other alkenes such as cyclopentene, cyclohex-
ene, and allyl alcohol. Unfortunately, they all led to their
respective cycloadducts in 510% yield. We are currently
examining this limitation.
22. The exo stereochemistry in 29 was assigned using NOE.
23. For an example, see: Powers, T. S.; Wulff, W. D.; Quinn,
J.; Shi, Y.; Jiang, W. Q.; Hsung, R. P.; Parisi, M.; Rahm,
A.; Jiang, X. W.; Yap, G. A.; Rheingold, A. L. J.
Organomet. Chem. 2001, 617, 182.
MHz, CDCl3) 30a: l 0.96 (d, 1H, J=10.5 Hz), 1.06 (d,
1H, J=10.8 Hz), 1.18–1.28 (m, 2H), 1.48–1.72 (m, 2H),
1.99 (d, 1H, J=5.4 Hz), 2.25 (d, 1H, J=4.2 Hz), 2.35 (d,
1H, J=4.2 Hz), 2.54–2.56 (m, 1H), 4.24 (dd, 1H, J=4.2,
8.7 Hz), 4.72 (t, 1H, J=9.0 Hz), 6.07 (dd, 1H, J=3.9, 9.0
Hz), 7.20–7.23 (m, 2H), 7.29–7.37 (m, 3H), 7.76 (d, 1H,
J=3.3 Hz); 30b: l 0.09 (d, 1H, J=11.4 Hz), 0.55 (d, 1H,
J=10.8 Hz), 1.18–1.28 (m, 2H), 1.48–1.72 (m, 2H), 1.98–
2.00 (m, 1H), 2.09 (d, 1H, J=4.8 Hz), 2.54–2.56 (m, 1H),