Low-energy pathway for Pauson-Khand reactions: Synthesis and reactivity of dicobalt hexacarbonyl complexes of chiral ynamines

Article abstract of DOI:10.1021/jo000278+

A family of dicobalt hexacarbonyl complexes of 1-(dialkylamino)-2-(trimethysilyl)acetylenes (3a-f) derived both from achiral and chiral amines [a, morpholine; b, (S)-2-methoxymethylpyrrolidine; c, (2R,5R)-2,5-bis(methoxymethyl)pyrrolidine; d, (±)-trans-2,5-bis(benzyloxymethyl)pyrrolidine; e, (2R,5R)-2,5-dimethylpyrrolidine; f, (S)-(α-methylbenzyl)benzylamine] has been prepared by a one-stage process from dichloroacetylene. The methanolysis at room temperature of these complexes (MeOH/K₂CO₃) induces the selective cleavage of the carbon-silicon bond, leading to the thermally unstable terminal ynamine complexes 12a-f. The Pauson-Khand reaction of 12a-f with strained olefins (norbornadiene and norbornene) takes place at unprecedentedly low temperatures (-35 °C) in the absence of chemical promoters. Diastereoselectivities of up to 94:6 are recorded in these reactions with the ynamine complexes derived from C₂ symmetrical chiral auxiliaries (12c,d). The high reactivity depicted by terminal ynamines in the Pauson-Khand reaction has been analyzed by theoretical semiempirical procedures [PM3(tm)] and with density functional theory (VWN/B88), and appears to reflect an easy CO loss from the ynamine-dicobalt hexacarbonyl complexes.

Full text of DOI:10.1021/jo000278+

J . Org. Chem. 2000, 65, 7291-7302
7291
Low -En er gy P a th w a y for P a u son -Kh a n d Rea ction s: Syn th esis
a n d Rea ctivity of Dicoba lt Hexa ca r bon yl Com p lexes of Ch ir a l
Yn a m in es
J aume Balsells, J ordi Va´zquez, Albert Moyano, Miquel A. Perica`s,* and Antoni Riera
Unitat de Recerca en S´ıntesi Asime`trica (URSA), Departament de Quı´mica Orga`nica,
Universitat de Barcelona, c/ Martı´ i Franque`s, 1-11, 08028-Barcelona, Spain
mapericas@qo.ub.es
Received February 29, 2000
A family of dicobalt hexacarbonyl complexes of 1-(dialkylamino)-2-(trimethysilyl)acetylenes (3a -f)
derived both from achiral and chiral amines [a , morpholine; b, (S)-2-methoxymethylpyrrolidine; c,
(2R,5R)-2,5-bis(methoxymethyl)pyrrolidine; d , (()-trans-2,5-bis(benzyloxymethyl)pyrrolidine; e,
(2R,5R)-2,5-dimethylpyrrolidine; f, (S)-(R-methylbenzyl)benzylamine] has been prepared by a one-
stage process from dichloroacetylene. The methanolysis at room temperature of these complexes
(MeOH/K2CO3) induces the selective cleavage of the carbon-silicon bond, leading to the thermally
unstable terminal ynamine complexes 12a -f. The Pauson-Khand reaction of 12a -f with strained
olefins (norbornadiene and norbornene) takes place at unprecedentedly low temperatures (-35
°C) in the absence of chemical promoters. Diastereoselectivities of up to 94:6 are recorded in these
reactions with the ynamine complexes derived from C2 symmetrical chiral auxiliaries (12c,d ). The
high reactivity depicted by terminal ynamines in the Pauson-Khand reaction has been analyzed
by theoretical semiempirical procedures [PM3(tm)] and with density functional theory (VWN/B88),
and appears to reflect an easy CO loss from the ynamine-dicobalt hexacarbonyl complexes.
Sch em e 1
In tr od u ction
Since its introduction in 1973, the Pauson-Khand
reaction (Scheme 1) has progressively gained importance
as a synthetic method for cyclopentenone synthesis.1
Depending on the substitution of the reacting olefin, up
to two chiral centers are created in this annulation, and
methods for controlling their absolute stereochemistry
have been explored from different perspectives.2,3
Up to now, the most successful approaches to enan-
tiocontrolled Pauson-Khand reactions have relied on the
use of chiral auxiliaries covalently bonded to either the
alkyne4 or the alkene reagents,5 and in fact, these
enantioselective versions of the process have been applied
in total synthesis.5a,6 In this context, we have systemati-
cally explored the use of acetylenic ethers4a-e and
thioethers4k-m as substrates for the reaction.
protocols involving auxiliary recovery, adducts 2 arising
from these reactions could be, in principle, elaborated to
(4) Acetylenic ethers: (a) Poch, M.; Valent´ı, E.; Moyano, A.; Perica`s,
M. A.; Castro Tetrahedron Lett. 1990, 31, 7505-8. (b) Verdaguer, X.;
Moyano, A.; Perica`s, M. A.; Riera, A.; Greene, A. E.; Piniella, J . F.;
Alvarez-Larena, A. J . Organomet. Chem. 1992, 433, 305-310. (c)
Bernardes, V.; Verdaguer, X.; Kardos, N.; Riera, A.; Moyano, A.;
Perica`s, M. A.; Greene, A. E. Tetrahedron Lett. 1994, 35, 575-578. (d)
Verdaguer, X.; Moyano, A.; Perica`s, M. A.; Riera, A.; Bernardes, V.;
Greene, A. E.; Alvarez-Larena, A.; Piniella, J . F. J . Am. Chem. Soc.
1994, 116, 2153-2154. (e) Verdaguer, X.; Va´zquez, J .; Fuster, G.;
Bernardes-Genisson, V.; Greene, A. E.; Moyano, A.; Perica`s, M. A.;
Riera, A. J . Org. Chem. 1998, 63, 7037-7052. Acetals of acetylenic
ketones: (f) Stolle, A.; Becker, H.; Salau¨n, J .; de Meijere, A. Tetrahe-
dron Lett. 1994, 35, 3521-3524. Esters of ynoic acids: (g) Fonquerna,
S.; Moyano, A.; Perica`s, M. A.; Riera, A. Tetrahedron 1995, 51, 4239-
4254. Amides of ynoic acids and related species: (h) Fonquerna, S.;
Moyano, A.; Perica`s, M. A.; Riera, A. J . Am. Chem. Soc. 1997, 119,
10225-10226. (i) Fonquerna, S.; Rios, R.; Moyano, A.; Perica`s, M. A.;
Riera, A. Eur. J . Org. Chem. 1999, 3459, 9-3478. (j) Balsells, J .;
Moyano, A.; Perica`s, M. A.; Riera, A. Org. Lett 1999, 1, 1981-1984.
Acetylenic thioethers: (k) Balsells, J .; Moyano, A.; Perica`s, M. A.; Riera,
A. Tetrahedron: Asymmetry 1997, 8, 1575-1580. (l) Montenegro, E.;
Poch, M.; Moyano, A.; Perica`s, M. A.; Riera, A. Tetrahedron 1997, 53,
8651-8664. (m) Montenegro, E.; Poch, M.; Moyano, A.; Perica`s, M. A.;
Riera, A. Tetrahedron Lett. 1998, 39, 335-338. Acetylenic sulfoxides:
(n) Montenegro, E.; Moyano, A.; Perica`s, M. A.; Riera, A.; Alvarez-
Larena, A.; Piniella, J . F. Tetrahedron: Asymmetry 1999, 10, 457-
471. (o) Adrio, J .; Carretero, J . C. J . Am. Chem. Soc. 1999, 121, 7411-
7412.
As a continuation of these efforts, we decided to test
the use of amines directly bonded to the unsaturated
system as chiral controllers for the Pauson-Khand
reaction. To this end, the almost unknown7 chiral
ynamines (1; see Chart 1) were selected as starting
materials. It is worth noting that, in addition to usual
(1) For recent reviews, see: (a) Chung, Y. K. Coord. Chem. Rev.
1999, 188, 297-341. (b) Schore, N. E. In Comprehensive Organome-
tallic Chemistry II; Hegedus, L. S., Ed.; Elsevier: Oxford, U.K., 1995;
Vol 12, pp 703-739.
(2) For the use of chiral phosphines bonded to cobalt, see: (a) Bladon,
P.; Pauson, P. L.; Brunner, H.; Eder, R. J . Organomet. Chem. 1988,
355, 449-454. (b) Brunner, H.; Niedernhuber, A. Tetrahedron: Asym-
metry 1990, 1, 711-714. (c) Park, H. J .; Lee, B. Y.; Kang, Y. K.; Chung,
Y. K. Organometallics 1995, 14, 3104-3107. (d) Hay, A. M.; Kerr, W.
J .; Kirk, G. G.; Middlemiss, D. Organometallics 1995, 14, 4986-4988.
(e) Castro, J .; Moyano, A.; Perica`s, M. A.; Riera, A.; Piniella, J . F.;
Alvarez-Larena, A. J . Organomet. Chem. 1999, 585, 53-58.
(3) For approaches based on the preferential oxidative removal of
CO from one of the diastereotopic cobalt atoms, see: (a) Kerr, W. J .;
Kirk, G. G.; Middlemiss, D. Synlett 1995, 1085-1086.
(5) Enol ethers: (a) Castro, J .; So¨rensen, H.; Riera, A.; Morin, C.;
Moyano, A.; Perica`s, M. A.; Greene, A. E. J . Am. Chem. Soc. 1990,
112, 9388-9389. (b) Castro, J .; Moyano, A.; Perica`s, M. A.; Riera, A.;
Greene, A. E. Tetrahedron: Asymmetry 1994, 5, 307-310.
10.1021/jo000278+ CCC: $19.00 © 2000 American Chemical Society
Published on Web 10/06/2000

7292 J . Org. Chem., Vol. 65, No. 22, 2000
Balsells et al.
Ch a r t 1
Sch em e 2
Sch em e 3
enantiomerically pure R-aminocyclopentanones and R-
aminocyclopentanols.8
We wish to disclose here our results in this area, which
cover the development of a high-yield one-pot procedure
for the preparation of dicobalt hexacarbonyl complexes
of chiral 1-amino-2-(trimethysilyl)acetylenes (3) from the
corresponding chiral amines and the evaluation of a
family of such chiral amines belonging to the C1 and C2
symmetry point groups as sterocontrollers in the Pau-
son-Khand reaction of ynamines. It has been established
from these studies that ynamines represent a new
paradigm of reactivity in Pauson-Khand reactions. An
explanation of this behavior has been provided on the
basis of theoretical studies.
from dichloroacetylene,13 and by Ficini, who converted
dichloroenamines into ynamines by treatment with base14
(Scheme 2).
Resu lts a n d Discu ssion
Trapping of the acetylide resulting from â-elimination
would then be done with trimethylsilyl chloride; besides
the known protecting effect of the triple bond exerted by
silyl substituents,15 we have previously shown that yields
of formation of dicobalt hexacarbonyl complexes of elec-
tron-rich terminal alkynes, which are necessary inter-
mediates for Pauson-Khand reactions, are highly in-
creased on silylation of the triple bond.4a Once this
beneficial effect has been exerted, desilylation can be
readily achieved by methanolysis in the presence of
potassium carbonate.16
Dichloroacetylene was prepared in ethereal solution
according to a previously reported procedure.17 Then, to
a cold (-70 °C) solution of 4, the secondary amines 6a -f
were added (Scheme 3), and interaction of these reagents
was maintained until complete addition, as indicated in
Table 1. The very unstable dichloroenamines 5a -f, which
were formed in essentially quantitative yield, were not
isolated. After vacuum removal at low temperature of
solvent and excess 4, the crude dichloroenamines were
converted to the silylynamines 7a -f by treatment with
2 equiv of n-BuLi (-70 to -10 °C) followed by quenching
with trimethylsilyl chloride (-10 °C to room tempera-
ture).
P r ep a r a t ion of Dicob a lt H exa ca r b on yl Com -
p lexes of Ch ir a l Tr im eth ylsilylyn a m in es. A first
target in the development of this project was the estab-
lishment of experimental conditions suitable for the high-
yield synthesis of ynamines9 derived from chiral second-
ary amines. The main restriction introduced by these
substances is economical: the high value of the enantio-
merically pure secondary amines makes advisable the
preparation of the corresponding ynamines on small
scale, whereas most reported syntheses of these com-
pounds are carried out on large scale, to mitigate
problems due to extremely easy hydrolysis during ma-
nipulation. Enhanced hydrolytic tendency and limited
thermal stability of terminal ynamines derived from
bulky, R-branched amines were other conceivable prob-
lems to be considered at the synthesis stage.
According to that, we planned to prepare the target
ynamines starting from dichloroacetylene (4) and use a
one-pot procedure similar to those previously developed
for alkoxyacetylenes,10 (alkylthio)acetylenes,11 and bis-
(alkylthio)acetylenes.4k,12 In the present instance, such
methodology would bridge previous work by Brandsma,
who reported on the preparation of dichloroenamines (5)
Crude silylynamines 7a -f were obtained in high yield
and were notably pure (1H and 13C NMR). According to
our expectations, they showed an enhanced hydrolytic
and thermal stability with respect to their terminal
counterparts; however, their manipulation is still almost
unavoidably accompanied by significant decomposition.
Bearing in mind our ultimate target, the crude silylyn-
amines 7a -f were treated with octacarbonyldicobalt to
produce in high yield complexes 3a -f. These are green
solids or oils (not red, as normally observed for alkyne-
dicobalt hexacarbonyl complexes), stable for months at
(6) Bernardes, V.; Kann, N.; Riera, A.; Moyano, A.; Perica`s, M. A.;
Greene, A. E. J . Org. Chem. 1995, 60, 6670-6671. (b) Tormo, J .;
Verdaguer, X.; Moyano, A.; Perica`s, M. A.; Riera, A. Tetrahedron 1996,
52, 14021-14040. (c) Castro, J .; Moyano, A.; Perica`s, M. A.; Riera, A.;
Greene, A. E.; Alvarez-Larena, A.; Piniella, J . F. J . Org. Chem. 1996,
61, 9016-9020. (d) Tormo, J .; Moyano, A.; Perica`s, M. A.; Riera, A. J .
Org. Chem. 1997, 62, 4851-4856.
(7) van Elburg, P. A.; Honig, G. W. N.; Reinhoudt, D. N. Tetrahedron
Lett. 1987, 28, 6397-6400.
(8) For applications of enantiomerically pure aminocyclopentanols,
see: Ramesh, N. G.; Klunder, A. J . H.; Zwannenburg, B. J . Org. Chem.
1999, 64, 3635-3641 and references therein.
(9) For some reviews, see: (a) Ficini, J . Tetrahedron 1976, 32, 1449-
1486. (b) Collard-Motte, J .; J anousek, Z. Top. Curr. Chem. 1986, 130,
89-131. (c) Booker-Milburn, K. I. In Comprehensive Organic Func-
tional Group Transformations; Katritzky, A. R., Meth-Cohn, O., Rees,
C. W., Eds. Elsevier: Oxford, U.K., 1995; Vol. 2, pp 1039-1074.
(10) Moyano, A.; Charbonnier, F.; Greene, A. E. J . Org. Chem. 1987,
52, 2919-2922.
(11) Nebois, P.; Kann, N.; Greene, A. E. J . Org. Chem. 1995, 60,
7690-7692.
(12) Riera, A.; Cabre´, F.; Moyano, A.; Perica`s, M. A., Santamar´ıa,
J . Tetrahedron Lett. 1990, 31, 2169-2172.
(13) van der Heiden, R.; Brandsma, L. Synthesis 1987, 76-77.
(14) Ficini, J .; Barbara, C. Bull. Soc. Chim. Fr. 1965, 2787-2793.
(15) Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic
Synthesis; Wiley-Interscience: New York, 1999; pp 654-656.
(16) Bernardes, V.; Verdaguer, X.; Moyano, A.; Perica`s, M. A.; Riera,
A.; Greene, A. E., J . Organomet. Chem. 1994, 470, C12-C14.
(17) Kende, A. S.; Fludzinski, P. Synthesis 1982, 455-456.

Low-Energy Pathway for Pauson-Khand Reactions
J . Org. Chem., Vol. 65, No. 22, 2000 7293
Ta ble 1. On e-P ot Syn th esis of Tr im eth ylsilylyn a m in es
(7a -f) a n d of th e Cor r esp on d in g Dicoba lt Hexa ca r bon yl
Com p lexes (3a -f)
Sch em e 4
able from 1-chloro-2-phenylacetylene (8).21 Both com-
pounds were prepared uneventfully and readily converted
to their dicobalt hexacarbonyl complexes 10a ,b (Scheme
4).
The Pauson-Khand reactions of 10a ,b with norbor-
nadiene took place with noticeable regioselectivity, ex-
clusively leading to R-aminocyclopentenones 11a ,b. In the
case of complex 10b, moreover, the reaction was notably
diastereoselective, the cyclopentenone adduct 11b being
obtained as a readily separable 4:1 mixture of diastere-
omers. On the negative side, the reactions required
rather drastic conditions to proceed and, probably as a
consequence, yields of 11a ,b were low.22 The idea that
steric effects by the bulky phenyl group could severely
hinder cobaltacycle formation en route to cyclopentenones
11a ,b is fully confirmed by the results of attempted
reactions of complexes 3a ,b, bearing an even bulkier
trimethylsilyl group, with the same olefin. No cyclopen-
tenone adduct could be detected in these cases.
In view of these results, we turned our attention to the
unsubstituted ynamines 1, which should be devoid of
unfavorable steric effects. For reactivity studies, dicobalt
hexacarbonyl complexes of unsubstituted ynamines 12a-f
were conveniently prepared through a one-pot process
from crude trimethylsilylynamines 7a -f as outlined in
Scheme 5. Complexes 12a -f, which are also green-
colored solids or oils, are highly unstable, decomposing
by CO loss with great ease. They could be stored under
CO for limited periods of time but, in practice, were best
prepared immediately prior to use.
room temperature provided that they are kept under CO
atmosphere, and can be easily purified by standard
chromatography. Overall yields for the preparation of
silylynamines (7a -f) and complexes (3a -f) are uniformly
high and have been summarized in Table 1.
It is to be mentioned that Himbert and co-workers have
explored a related approach to ynamines where the base
employed for the generation of dichloroacetylene is the
lithium amide of the secondary amine which has to be
subsequently added to the generated triple bond.18 When
this elegant, atom-economical approach was applied to
the bulky amines in the present study, the yields of
ynamine 7 were ca. 30% lower than generating dichlo-
roacetylene in a separate step.19
P a u son -Kh a n d Rea ction s of Yn a m in es. The Pau-
son-Khand chemistry of ynamines has remained unex-
plored. The only related reports describe the cycloaddi-
tions of N-(1-alkynyl)sulfonamides or N-(1-alkynyl)-
carboxamides, in which the electron-donating nature of
the nitrogen atom has been deeply modified.20 For simple
ynamines, possessing electronically richer triple bonds,
substantial differences in reactivity toward olefins could
be anticipated.
To get a complete picture of the behavior of these
alkynes in the reaction, we decided to study both unsub-
stituted ynamines 1 and their C-substituted congeners.
Among these last substrates, we selected the 1-(dialkyl-
amino)-2-phenylacetylenes 9a ,b, which are readily avail-
The Pauson-Khand reactions of complexes 12a -f with
strained olefins [norbornadiene (NBD) and norbornene
(NB)] were next studied under both thermal (A) and
amine oxide promoted23 (B) conditions, to afford the
tricyclic adducts 13a -d and 14b-d as shown in Scheme
6. Relevant information for these reactions has been
summarized in Table 2.
(18) Himbert, G.; Nasshan, H.; Gerulat, O. Synthesis 1997, 293-
294.
(19) This is probably due to the coexistence in the reaction medium
of dichloroenamine 5 and lithium amide. The formation of 1,1-bis-
(dialkylamino)-2-chlorethenes has been reported by Brandsma under
these conditions.12
(20) Witulski, B.; Stengel, T. Angew. Chem., Int. Ed. Engl. 1998,
37, 489-492. (b) Witulski, B.; Go¨ssmann, M. Chem. Commun. 1999,
1879. For the use of N-tosylynamines in a related 2 + 2 + 1 cobalt-
mediated cycloaddition, see: Rainier, J . D.; Imbriglio, J . E. Org. Lett.
1999, 1, 2037-2039.
The most noticeable observation on these processes is
the unprecedentedly high reactivity of the ynamine
(21) Viehe, H. G.; Reinstein, M. Angew. Chem., Int. Ed. Engl. 1964,
3, 506.
(22) Promotion of the reactions by NMO23 led to diminished yields:
15% of 11a and 0% of 11b.
(23) Shambayati, S.; Crowe, W. E.; Schreiber, S. L. Tetrahedron Lett.
1990, 31, 5289-5292.

7294 J . Org. Chem., Vol. 65, No. 22, 2000
Balsells et al.
Sch em e 5
with NBD (entries 4, 9, and 19) take place at reasonable
rate, and in the case of complex 12c it has been possible
to conduct the reaction at -35 °C (entry 10). These low-
temperature, thermal reactions are also possible with
NB, but require considerably longer periods of time for
complete disappearance of the initial complexes (entries
14 and 23).
In general, for a certain complex/olefin pair, performing
the reaction with chemical activation by NMO represents
an important acceleration. Given the intrinsically high
reactivity of the starting ynamine complexes, the most
important practical application that can be drawn from
this observation is from low-temperature reactions, which
take place to completion in rather short periods of time
(entries 5, 7, 12, 15, 20, and 24).
Sch em e 6
Although the yields of the Pauson-Khand cycloaddi-
tions of complexes 12 were only moderate, the reactions
took place cleanly and adducts 13 or 14 were the only
defined products arising from the ynamine complexes.
From the point of view of stereochemical outcome,
complex 12b, containing a singly R-substituted amine,
reacts with strained olefins with poor diastereoselectivity.
Moreover, the diastereoselectivity/temperature profile
exhibited by the reactions of 12b is essentially flat
(compare entries 2 and 4). With complexes 12c,d , con-
taining a C2 symmetrical amine, the situation is quite
different. Thus, even at room temperature (entries 8, 13,
17, and 21) high diastereoselectivities are observed with
the studied olefins and, for any of the C2 auxiliaries, the
observed diastereoselectivity sharply increases as the
reaction temperature is lowered. Adduct 13c can be
obtained with a maximum 94:6 diastereoselectivity (dr
15.6:1; entry 12) by performing the reaction with NMO
as a chemical promoter at -30 °C. Very interestingly,
the reaction is complete in only 5 h at this very low
temperature. On the other hand 14c, which arises from
the same ynamine reacting with norbornene, is obtained
with a maximum 89.5:10.5 diastereoselectivity (dr 8.5:1;
entry 14) by conducting the cycloaddition under purely
thermal conditions at -21 °C.
With the bulkier trans-2,5-bis(benzyloxymethyl)pyr-
rolidine as the chiral auxiliary, thermal reactions tend
to be slightly slower but take place with considerably
higher yields. Adduct 13d , containing this auxiliary and
arising from the reaction with NBD, can be obtained as
an 88.5:11.5 mixture of diastereomers (dr 7.7:1, entry 20)
by performing the process at -21 °C with chemical
activation. Finally, adduct 14b (involving the use of
norbornene) is obtained in 49% yield as a 90:10 diaster-
eomeric mixture (dr 9.1:1; entry 23) through a thermal
reaction at -21 °C.
All of the Pauson-Khand adducts reported in Table 2
are oily materials that could be easily purified by column
chromatography and exhibited good chemical stability.
Diastereomeric separation, however, proved to be much
more difficult than in the case of adduct 11b and could
not be performed.
Ra tion a liza tion of th e Rea ctivity Beh a vior of
Yn a m in es in th e P a u son -Kh a n d Cycloa d d ition .
The very high reactivity depicted by ynamines in the
purely thermal intermolecular Pauson-Khand reaction,
which greatly exceeds that observed for closely related
alkyne derivatives also containing an electron-rich triple
bond,25 was a striking observation. The existence of some
correlation between reactivity and electronic nature of
the triple bond was strongly indicated by the fact that
Ta ble 2. P a u son -Kh a n d Rea ction s of Ch ir a l Ter m in a l
Yn a m in es w ith Str a in ed Alk en es
starting
reacn conditionsb
product
entry complex alkenea (temp (°C), time (h)) (yield (%), drc)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
12a
12b
NBD
NBD
NBD
NBD
NBD
NB
A (22, 0.03)
A (22, 0.03)
A (0, 1)
13a (78, -)
13b (41, 1.6:1)
13b (44, 1.6:1)
13b (77, 1.8:1)
13b (68, 2.3:1)
14b (22, 2.0:1)
14b (22. 2.4:1)
13c (22, 4.5:1)
13c (30, 7.3:1)
13c (22, 8.0:1)
13c (18, 4.9:1)
13c (18, 15.6:1)
14c (27, 5.3:1)
14c (20, 8.5:1)
14c (17, 7.4:1)
14c (17, 7.5:1)
13d (24, 2.4:1)
13d (32, 4.6:1)
13d (32, 7.0:1)
13d (34, 7.7:1)
14d (51, 5.9:1)
14d (49, 6.4:1)
14d (49, 9.1:1)
14d (45, 6.8:1)
A (-21, 24)
B (-30, 12)
A (22, 0.5)
B (-21, 12)
A (22, 0.08)
A (-21, 12)
A (-35, 72)
B (-20, 3)
B (-30, 5)
A (22, 0.08)
A (-21, 144)
B (-20, 24)
B (-30, 72)
A (22, 0.17)
A (0, 1.5)
A (-21, 12)
B (-21, 4)
A (22, 0.08)
A (0, 1.5)
A (-21, 168)
B (-21, 6)
NB
12c
NBD
NBD
NBD
NBD
NBD
NB
NB
NB
NB
NBD
NBD
NBD
NBD
NB
NB
NB
NB
12d
a
b
NBD ) norbornadiene; NB ) norbornene. A ) The olefin (10
equiv) was added to a solution of complex 12 in toluene at the
specified temperature. B ) Anhydrous NMO (6 equiv) and the
olefin (10 equiv) were added to a dichloromethane solution of
complex 12 at the specified temperature. Reaction times are for
complete conversion. c Determined by HPLC.
complexes 12a -d toward strained olefins.24 Thus, the
reactions with NBD at room temperature are complete
within 2-10 min (entries 1, 2, 8, and 17), while with the
less reactive NB slightly longer (5-30 min) reaction times
are needed for complete consumption of the starting
complex. The reactivity of these ynamine complexes is so
high that, even at -20 °C, the purely thermal reactions
(24) It is to be mentioned that complexes 12e and 12f, which have
not been included in Table 2, appear to react with NBD and NB in a
much similar manner that of 12a -d . However, any attempted isolation
of the corresponding adducts involving chromatographic purification
unavoidably leads to complete decomposition.

Low-Energy Pathway for Pauson-Khand Reactions
J . Org. Chem., Vol. 65, No. 22, 2000 7295
Sch em e 7
the structurally related N-(1-alkynyl)sulfonamides, pos-
sessing an electronically poorer triple bond, require much
higher temperatures to react. However, if one considers
the geometric and electronic modifications suffered by the
acetylenic bond upon complexation, the transmission
(and even the nature) of the effects exerted by the alkyne
substituents was much less clear.27
To shed some light on this behavior we decided to
comparatively analyze by theoretical means28 the ther-
mochemistry of the steps which are believed to be
kinetically relevant in the Pauson-Khand reactions of
propyne (taken as an example of alkyne with normal
reactivity) and of N,N-(dimethylamino)acetylene (a simple
terminal ynamine) with ethylene. These steps (Scheme
7) are the initial dissociative loss of a CO ligand, which
generates a free coordination site for the entrance of the
reacting olefin, and the evolution of the so-generated
olefin complex into a cobaltacycle.
mented in the Spartan suite of programs.30 For the
dissociative step A, the loss of each of the three distinct
CO ligands in each starting complex (Ia ,b) was consid-
ered. Moreover, the possible conformers generated by
rotation around the C-N bond were considered in the
case of Ib. In each case, the most stable pentacarbonyl
complex presented a CO-bridged structure and was
generated by the loss of a distal (with respect to R)
equatorial CO ligand. Since it is known that cobalt
carbonyl complexes of alkynes present fluxional charac-
ter, all possible olefin-substituted complexes III were also
examined. Again, it was found in both cases that com-
plexes containing the olefin ligand at a distal equatorial
site were considerably more stable (6-7 kcal.mol-1) than
any other stereoisomer. We finally considered the ener-
getics of cobaltacycles IV arising from complexes III, with
the restriction of considering only those able to lead to
an R-substituted cyclopentenone, as experimentally ob-
served.
When the energetics of the overall CO/CH2dCH2
substitution process (step I f III: a , -5.5 kcal.mol-1; b,
-5.2 kcal.mol-1) and cobaltacycle formation (step III f
IV: a , -37.6 kcal.mol-1; b, -37.1 kcal.mol-1) are consid-
ered, the two systems appear to be completely equivalent.
However, if the dissociative step A is considered, the loss
of carbon monoxide is predicted to be up to 7.9 kcal.mol-1
easier in the case of the (dimethylamino)acetylene com-
plex Ia . Interestingly enough, this is in complete agree-
ment with the experimental observation of the poor
thermal stability of ynamine complexes 3a -f and 12a -
f, which have to be stored under a CO atmosphere to
prevent decarbonylation.
For an initial screening, we examined these processes
by the semiempirical PM3(tm) procedure,29 as imple-
(25) The reaction of the dicobalt hexacarbonyl complexes of acety-
lenic ethers with norbornene at 65 °C in isooctane requires 18 h for
completion,4c while the reaction of the corresponding complex of
(phenylthio)acetylene with norbornadiene in toluene is complete after
5 h at 60-70 °C.26
(26) Daalman, L.; Newton, R. F.; Pauson, P. L.; Wadsworth, A. J .
Chem. Res., Miniprint 1984, 3150-3164.
(27) For a discussion of changes in the reactivity of alkynes upon
coordination to cobalt, see: Happ, B.; Bartik, T.; Zucchi, C.; Rossi, M.
C.; Ghelfi, F.; Pa´lyi, G.; Va´radi, G.; Szalontai, G.; Horvath, I. T.; Chiesi-
Villa, A.; Guastini, C. Organometallics 1995, 14, 809-819.
(28) For previous theoretical descriptions of bonding in dicobalt
hexacarbonyl complexes of acetylenes with the extended Hu¨ckel
formalism, see: (a) Thorn, D. L.; Hoffmann, R. Inorg. Chem. 1978, 17,
126-140. (b) Hoffman, D. M.; Hoffmann, R.; Fisel, C. R. J . Am. Chem.
Soc. 1982, 104, 3858-3875. (c) Pepermans, H.; Hoogzand, C.; Geer-
lings, P. J . Organomet. Chem. 1986, 306, 395-405. (d) Halet, J . F.;
Saillard, J . Y. J . Organomet. Chem. 1987, 327, 365-77.
To examine this phenomenon more closely, the struc-
tures of the dicobalt hexacarbonyl complexes Ia ,b were
(29) PM3(tm) is
a modification of the original PM3 procedure
(Stewart, J . J . P. J . Comput. Chem. 1989, 10, 209-220) including a
parametrization for transition metals.
(30) SPARTAN, version 5.0, Wavefunction, Inc., 18401 Von Karman
Ave., Suite 370, Irvine, CA 92612.

7296 J . Org. Chem., Vol. 65, No. 22, 2000
Balsells et al.
tion of the amino substituent.36 In complete agreement
with this interpretation, when the dimethylamino group
in Ib was rotated by 90° to disrupt the hyperconjugation
with the CR-Co2 bond and the molecular geometry was
reoptimized with this restriction, some important geo-
metric changes took place: (i) The nitrogen atom became
pyramidal. (ii) The N-CR distance increased from 1.356
to 1.392 Å. (iii) The difference in length between the CR-
Co1 and CR-Co2 bonds was greatly reduced, passing from
0.150 to 0.033 Å. From the energetic point of view, the
electronic energy of this rotationally perturbed structure
was 13.6 kcal.mol-1 higher than that of Ib. It is thus clear
that hyperconjugation plays an important role in dictat-
ing the conformational preferences of Ib and in deter-
mining its geometric characteristics.
F igu r e 1. DFT-Optimized geometries and electronic energies
(VWN/B88) of the dicobalt hexacarbonyl complexes Ia ,b. (ax
) axial; ep ) equatorial proximal; ed ) equatorial distal).
It is interesting to realize that the structural phenom-
ena in Ib bear some analogy with the well-documented
stabilization of propargyl cations by dicobalt hexacarbo-
nyl complexes.37 In these cases, it is assumed that the
direction of the electron density flow is from the cluster
toward the propargyl carbon,38 and the phenomenon can
be described as an example of (positive or cationic)
hyperconjugation.
Ta ble 3. Releva n t Dista n ces (Å) in th e DF T (VWN/B88)
Op tim ized Geom etr y of th e Dicoba lt Hexa ca r bon yl
Com p lexes of P r op yn e (Ia ) a n d
(Dim eth yla m in o)a cetylen e (Ib)
parama
Ia
Ib
CR-CH3
CR-N(CH3)2
CR-Câ
1.513
1.355
1.369
2.014
2.166
2.016
1.995
2.618
1.850
1.825
1.861
1.847
1.809
1.871
1.345
2.059
2.058
2.037
2.038
2.576
1.875
1.835
1.882
1.875
1.836
1.882
Centering now our attention on the origin of the easy
loss of CO from Ib, it is important to realize that, as a
consequence of hyperconjugation, the Co2 cobalt atom in
Ib should become more electronically rich (as it is the
case), and this should be reflected in shorter Co2-CO
distances as a consequence of increased back-bonding
capacity in the metal.39 When the Co1-CO and Co2-CO
distances in Ib are compared, it can be seen that this is
in fact the case except for the Co2-COed bond in Ib, which
is elongated. Since this bond is trans to the CR-Co2 one
in the distorted octahedral coordination sphere of the Co2
atom, it seems that the dimethylamino substituent is
assisting and directing the dissociative loss of CO through
a trans effect,40 as pictorially represented by the reso-
nance structures in Figure 2.
C
R-Co1
CR-Co2
Câ-Co1
Câ-Co2
Co1-Co2
Co1-COep
Co1-COax
Co1-COed
Co2-COep
Co2-COax
Co2-Coed
a
As defined in Figure 1.
submitted to full geometry optimization using ab initio
DFT theory (VWN/B88),31 as implemented in the ADF
code, and using the ADF II(DZ)-SC basis set.34 The
results of this study have been summarized in Figure 1
and Table 3.
(35) Negative hyperconjugation occurs in X-C-Y systems where
X is an atom bearing one or more nonbonding electron pairs and the
C-Y bond is characterized by a low-lying LUMO, when a electron pair
on X is oriented antiperiplanar to the C-Y bond. The geometrical
consequences of hyperconjugation are the shortening of the C-X bond
and the lengthening of the C-Y bond. The stabilization arising from
such phenomenon can be rationalized in terms of double bond-no bond
resonance: X-C-Y S (+)XdC Y(-). For a discussion on the impor-
tance of negative hyperconjugation, see: Schleyer, P. v. R.; Kos, A. J .
Tetrahedron 1983, 39, 1141-1150.
(36) The term anomeric effect is normally used to jointly designate
the preference for conformational arrangements allowing the existence
of negative hyperconjugation and the consequences (enthalpic, geo-
metric, and kinetic) of this phenomenon. For recent, general references
on this topic, see: (a) The Anomeric Effect and Associated Stereoelec-
tronic Effects; ACS Symposium Series 539; Thatcher, G. R. J ., Ed.;
American Chemical Society: Washington, DC, 1993. (b) J uaristi, E.
The Anomeric Effect; CRC Press: Boca Raton, FL, 1994. For an
example of anomeric interaction involving a Mn(CO)5 fragment as a
C-2 substituent on a tetrahydropyranyl ring, see: DeShong, P.; Lessen,
T. A.; Le, T. X.; Anderson, G.; Sidler, D. R.; Slough, G. A.; von
Philipsborn, W.; Vo¨hler, M.; Zerbe, O. In The Anomeric Effect and
Associated Stereoelectronic Effects; ACS Symposium Series 539;
Thatcher, G. R. J ., Ed.; American Chemical Society: Washington, DC,
1993; pp 227-239.
An analysis of the geometric parameters in these
molecules helps in understanding the mechanism by
which the dimethylamino substituent facilitates the
dissociative loss of CO. In a comparison of the hexacar-
bonyl complexes Ia ,b, it is interesting to observe that,
whereas Ia is perfectly symmetrical, in Ib the CR-Co1
and CR-Co2 bonds show important differences in length,
the later being longer by 0.150 Å. An inspection of the
structure of Ib in Figure 1 provides an explanation for
this behavior: The nitrogen atom in the dimethylamino
substituent is essentially planar, and the conformation
of this unit is such that the nitrogen lone pair can
partially be delocalized into the CR-Co2 σ* orbital giving
rise to a (negative or anionic) hyperconjugative interac-
tion.35 In other words, an anomeric effect appears to exist
in the N-CR-Co2 fragment, as dictated by the conforma-
(31) Calculations performed using the VWN local functional32 with
Becke’s 1988 (B88) nonlocal exchange correction.33
(32) Vosko, S. H.; Wilk, L.; Nusair, M. Can. J . Phys. 1980, 58, 1200-
1211.
(33) Becke, A. D. Phys. Rev. A 1988, 38, 3098-3100.
(34) Baerends, E. J .; Ellis, D. E.; Ros, P. E. Chem. Phys. 1973, 2,
41-51. (b) Baerends, E. J .; Ellis, D. E.; Ros, P. E. Chem. Phys. 1973,
2, 52-59. (c) te Velde, G.; Baerends, E. J . J . Comput. Phys. 1992, 99,
84-98.
(37) For leading references, see: (a) Caffyn, A. J . M.; Nicholas, K.
M. In Comprehensive Organometallic Chemistry II; Hegedus, L. S., Ed.;
Elsevier: Oxford, U.K., 1995; Vol. 12, pp 685-702. (b) Nicholas, K.
M. Acc. Chem. Res. 1987, 20, 207-214.
(38) Schreiber, S. L.; Klimas, M. T.; Sammakia, T. J . Am. Chem.
Soc. 1987, 109, 5749.
(39) Cotton, F. A.; Wilkinson, G.; Murillo, C. A.; Bochmann, M.
Advanced Organic Chemistry, 6th ed.; Wiley-Interscience: New York,
1999; pp 636-639.

Low-Energy Pathway for Pauson-Khand Reactions
J . Org. Chem., Vol. 65, No. 22, 2000 7297
Sch em e 8
F igu r e 2. Anomeric (N-C-Co) and trans (C-Co-CO) effects
in Ib facilitating the dissociative loss of CO. Some CO ligands
have been omitted for clarity.
Ra tion a liza tion of th e Obser ved Dia ster eoselec-
t ivit y in t h e P a u son -Kh a n d Cycloa d d it ion s of
Yn a m in es. Regarding diastereoselectivity, the Pauson-
Khand reaction has normally been analyzed by compar-
ing, on the basis of either qualitative41 or quantitative
arguments,4e,42 the relative stabilities of the diastereo-
meric cobaltacycles which are assumed to intermediates
in the commonly accepted mechanism of the process.1
According to this mechanism, cobaltacycle formation is
the product-determining step, i.e., where the regio- and
the stereochemistry of the cyclopentenone products is
fixed.
In the case of ynamines the great facility of the initial
dissociative loss of CO we have just discussed tells in
favor of cobaltacycle formation being kinetically impor-
tant, so that the assumption of the existence of a
parallelism between the relative energies of these co-
baltacycles and those of the transition states leading to
them (Hammond postulate) seems fully justified. Accord-
ing to this, the greater the energy difference between the
diastereomeric cobaltacycle intermediates in a given
reaction, the higher the diastereoselectivity of the process
should be.
To analyze the differences in the diastereoselectivity
of the Pauson-Khand reactions of ynamines derived from
amines structurally similar but belonging to the C1 and
the C2 point groups (like 6b,c), we decided to perform a
PM3(tm) study of the cobaltacycle intermediates in the
reactions of ynamine complexes 12b,c with norborna-
diene. For comparison purposes, we selected the chiral
auxiliaries as belonging to the same enantiomeric se-
ries: (R)-6b and (R,R)-6c. Since it is well-known that
NBD exclusively reacts through its exo face,1 and it has
been established that only cobaltacycles with the Co(CO)3
and CH2 (bridge) moieties in a distal arrangement are
energetically viable,4e the only source of stereochemical
diversity in these processes is the nature [CoR (pro-R) or
CoS (pro-S)] of the cobalt atom of the starting complex
involved in the formation of the cobaltacycle (Scheme 8).
The classical view in comparing the efficiency as a
chiral auxiliary of 2-(methoxymethyl)pyrrolidine (6b) and
trans-2,5-bis(methoxymethyl)pyrrolidine (6c) is based on
the consideration that the system containing the C2
symmetrical amine has many less available conforma-
tions, since neither the rotation around the substrate-
nitrogen bond nor the inversion at nitrogen generates a
new conformer.43 In a parallel manner, less competing
conformationally isomeric transition states should exist
in the reactions of the system containing the C2 sym-
metrical amine, and an efficient transmission of the
stereochemical information of the chiral auxiliary toward
the newly created stereocenters should be possible in all
of them. In agreement with this view, up to 8 conforma-
tional minima were located for any of the two diastere-
omeric cobaltacycles arising from 12b, which contain 6b
as the chiral auxiliary. We have represented in Figure 3
(top) the most stable conformers of the cobaltacycles
involving each of the diastereotopic cobalt atoms in 12b.
As it can be seen, the one involving the CoS cobalt atom
is predicted to be 1.5 kcal.mol-1 more stable than the one
involving the CoR cobalt atom.
For each of the cobaltacycles arising from 12c, which
contain the C2 symmetrical amine 6c as the chiral
auxiliary, only two conformational minima could be
located. The most stable ones have been represented in
Figure 3 (bottom). Also in this case the cobaltacycle
involving the CoS cobalt atom is predicted to be the most
stable one, and the energy difference with the one
involving the CoR cobalt atom is now 2.3 kcal.mol-1
.
Thus, the present theoretical calculations provide an
explanation for the observation of diastereoselectivity in
the Pauson-Khand reactions of the ynamine complexes,
since they predict the existence of significant energy
differences between the cobaltacycles leading to the two
possible diastereomers of the reaction products. More-
over, the calculations succeed in predicting that the use
of C2 symmetrical amines as chiral auxiliaries will lead
to increased diastereoselectivities.
(40) Although trans influences (structural) and effects (kinetic) are
most common in square planar complexes, they are not rare in
octahedral ones. An illustrative example is provided by [Co(NH3)5(CH3)]-
S2O6, in which the Co-N bonds cis to the strong σ-donor methyl group
exhibit distances in the range 1.957-1.969 Å, whereas the trans Co-N
bond is much longer (2.127 Å). See: Kofod, P.; Harris, P.; Larsen, S.
Inorg. Chem. 1997, 36, 2258-2266.
(41) Magnus, P.; Exon, C.; Albaugh-Robertson, P. Tetrahedron 1985,
41, 5861-5869. (b) Magnus, P.; Principe, L. M. Tetrahedron Lett. 1985,
26, 4851-4854.
(42) Castro, J .; Moyano, A.; Perica`s, M. A.; Riera, A. Tetrahedron
1995, 51, 6541-6556.
(43) For some reviews, see: (a) Whitesell, J . K. Chem. Rev. 1989,
89, 1581-1590. (b) Rosini, C.; Franzini, L.; Raffaelli, A.; Salvadori, P.
Synthesis 1992, 503-517.

7298 J . Org. Chem., Vol. 65, No. 22, 2000
Balsells et al.
performed by the “Servicio de Espectrometr´ıa de Masas,
Universidad de Co´rdoba”. Solutions of dichloroacetylene in
diethyl ether were prepared by the method of Kende.17
(Wa r n in g! Dichloroacetylene is toxic and explosive. Although
this procedure appears to be completely safe, it is strongly
recommended that all work with dichloroacetylene be conducted
in a hood and behind appropriate shielding.) (S)-2-(Methoxy-
methyl)pyrrolidine,44 (2R,5R)-2,5-bis(methoxymethyl)pyrroli-
dine,45 and (2R,5R)-2,5-dimethylpyrrolidine46 were prepared
according to reported procedures. (()-trans-2,5-Bis(benzyl-
oxymethyl)pyrrolidine47 was prepared by alkylation of (()-
trans-2,5-bis(hydroxymethyl)pyrrolidine.45
Gen er a l P r oced u r e for th e Syn th esis of Dicoba lt
Hexa ca r bon yl Com p lexes of Tr im eth ylsilylyn a m in es.
Hexa ca r bon yl(µ-(η-1-m or p h olin o-2-(tr im eth ysilyl)a cety-
len e))d icoba lt(Co-Co), 3a . Freshly distilled morpholine (6a )
(522 mg, 6.0 mmol) was added to a solution of 8.0 mmol of
dichloroacetylene (4) in 5 mL of diethyl ether cooled to -70
°C. The mixture was then allowed to warm to room temper-
ature, heated to 33 °C for 30 min, and cooled again to -70 °C.
Solvent and excess dichloroacetylene were eliminated at
reduced pressure at that temperature. The crude dichloroe-
namine (5a ) was dissolved in 15 mL of diethyl ether, cooled to
-70 °C, and n-BuLi (8.25 mL, 13.2 mmol, 1.6 M in hexanes)
was added via syringe. The temperature was slowly raised to
-10 °C, and 0.91 mL (7.2 mmol) of chlorotrimethylsilane was
added via syringe. The mixture was then allowed to warm to
room temperature, 10 mL of anhydrous hexane was added,
and after 15 min, the mixture was filtered through a pad of
Celite under nitrogen. Solvent evaporation at reduced pressure
afforded 980 mg of the crude trimethylsilylynamine 7a as a
colorless oil.
F igu r e 3. PM3(tm)-optimized geometries of the most stable
conformers of the putative cobaltacycles leading to 13b,c.
A small sample of this oil (98 mg) was dissolved in 2 mL of
anhydrous pentane, and the resulting solution was transferred
to another flask containing a solution of 185 mg (0.54 mmol)
of Co2(CO)8 in 4 mL of pentane. Gas evolution was observed,
as the solution became green in color. After 15 min of stirring
at room temperature, the mixture was concentrated to 1/3 of
its initial volume under a mild CO stream and directly
introduced in a chromatographic column (2.5% v/v triethyl-
amine pretreated SiO2), and elution with hexane/dichlo-
romethane mixtures of increasing polarity was started. Com-
plex 3a (226 mg) could be isolated from the eluate as a green
solid (80% yield, based on initial morpholine): IR (film) νmax
Con clu sion s
In summary, we have developed an efficient one-stage
method for the conversion of chiral secondary amines into
the hexacarbonyldicobalt complexes of the corresponding
trimethylsilylynamines. We have also shown that the
desilylation of these species is a convenient method for
the preparation of the very unstable dicobalt hexacar-
bonyl complexes of terminal ynamines.
The reactivity of these last complexes toward strained
olefins for cyclopentenone building (the Pauson-Khand
reaction) is the highest ever recorded under purely
thermal conditions, the process taking place even at -35
°C. With complexes containing C2 symmetrical amines,
the possibility of performing Pauson-Khand reactions
at such low temperatures allows the achievement of high
levels of diastereoselectivity.
According to semiempirical and density functional
theory calculations, the increased reactivity of ynamine
complexes has its origin in the unusually easy dissocia-
tive loss of CO in the derived dicobalt hexacarbonyl
complexes. This behavior, in turn, seems to arise from
an anomerically assisted and directed dissociative loss
of CO. Such stabilization should be absent (or present to
a much lesser extent) in N-(1-alkynyl)amides which, as
we have already commented, only undergo intermolecu-
lar Pauson-Khand reaction at much higher tempera-
tures.
2090, 2050, 2010, 1600 cm-1 1H NMR (300 MHz, CDCl3) δ
;
0.32 (s, 9H), 2.93 (br, 4H), 3.75 (br, 4H); 13C NMR (75 MHz,
CDCl3) δ 1.1 (3CH3), 53.9 (2CH2), 66.2 (2CH2), 68.0 (Cq), 133.2
(Cq), 200.0 (CO); MS (FAB-NBA) m/z (relative intensity) 469
(M+, 14), 441 (M+ - CO, 100), 413 (M+ - 2CO, 100).
H exa ca r b on yl-µ-(η -1-[(S)-2-m et h oxym et h ylp yr r oli-
d in o]-2-(tr im eth ysilyl)a cetylen e)-d icoba lt (Co-Co), 3b.
The above procedure was followed starting from a solution of
10.0 mmol of 4 in 6 mL of diethyl ether and 690 mg (6.0 mmol)
of (S)-(-)-2-methoxymethylpyrrolidine (6b). The reaction
leading to the dichloroenamine 5b was carried out for 2 h at
0 °C. After that time, 8.25 mL (13.2 mmol, 1.6 M in hexanes)
of n-BuLi were used for the elimination/transmetalation step,
and 0.91 mL (7.2 mmol) of chlorotrimethylsilane were used to
trap the lithium acetylide. After filtration and solvent removal,
1.10 g of the crude trimethylsilylynamine 7b was obtained as
a brown oil.
A portion of this oil (110 mg) was dissolved in 3 mL of
pentane and the resulting mixture added to a solution of 178
mg (0.52 mmol) of Co2(CO)8 in 5 mL of pentane. After 15 min
stirring at room temperature and column chromatography, 3b
(243 mg) was isolated as a green oil (81% yield based on the
starting amine 6b): IR (film) νmax 2080, 2040, 2010, 1600 cm-1
.
The operation of anomeric effects in the dicobalt
hexacarbonyl complexes of ynamines is being currently
investigated in our laboratories by accurate DFT theory
and will be reported separately.
1H NMR (300 MHz, CDCl3) δ 0.32 (s, 9H), 0.85 (br, 2H), 1.24
(44) Enders, D.; Fey, P.; Kipphardt, H. Org. Synth. 1987, 65, 173-
182.
(45) Chen, L.-y. Ph.D. Thesis, Universite´ Catholique de Louvain,
1991.
(46) Short, R. P.; Kennedy, R. M.; Masamune, S. J . Org. Chem. 1989,
54, 1755-1756.
(47) Marzi, M.; Misiti, D. Tetrahedron Lett. 1989, 30, 6075-6076.
Exp er im en ta l Section
Gen er a l Meth od s. General experimental aspects have
been published elsewhere.4e High-resolution mass spectra were

Low-Energy Pathway for Pauson-Khand Reactions
J . Org. Chem., Vol. 65, No. 22, 2000 7299
(br, 2H), 1.90 (br, 2H), 2.80-3.00 (m, 1H), 3.33 (s, 3H), 3.20-
3.60 (m, 2H). 13C NMR (75 MHz, CDCl3) δ 1.4 (3CH3), 24.0
(CH2), 28.8 (CH2), 55.3 (CH2), 59.0 (CH3), 64.8 (CH), 70.0 (Cq),
72.9 (CH2), 129.5 (Cq), 200.9 (CO). MS (FAB-NBA) m/z
(relative intensity) 469 (M+ - CO, 24), 441 (M+ - 2CO, 97),
413 (M+ - 3CO, 51), 385 (M+ - 4CO, 100).
Hexa ca r bon yl(µ-(η -1-[(R,R)-2,5-bis(m eth oxym eth yl)-
p yr r olid in o]-2-(t r im et h ysilyl)a cet ylen e))d icob a lt (Co-
Co), 3c. The general procedure was followed starting from a
solution of 8.0 mmol of 4 in 5 mL of diethyl ether and 636 mg
(4.0 mmol) of (R,R)-2,5-bis(methoxymethyl)pyrrolidine (6c).
The reaction leading to the dichloroenamine 5c was carried
out for 2 h at 20 °C. After that time, 5.5 mL (8.8 mmol, 1.6 M
in hexanes) of n-BuLi was used for the elimination/transmeta-
lation step, and 0.60 mL (4.8 mmol) of chlorotrimethylsilane
was used to trap the lithium acetylide. After filtration and
solvent removal, 985 mg of the crude trimethylsilylynamine
7c was obtained as a brown oil.
6H), 1.50-1.60 (m, 2H), 2.05-2.25 (m, 2H), 3.5-3.7 (m, 2H);
13C NMR (75 MHz, CDCl3) δ 1.9 (3CH3), 18.4 (2CH3), 30.7
(2CH2), 59.7 (2CH), 201.5 (CO). Absorption for the triple bond
carbon atoms was not observed. MS (FAB-NBA) [m/z (relative
intensity)]: 481 (M+, 5%), 453 (M+ - CO, 100%).
H e xa ca r b on yl(µ-(η-1-[(S )-(r-m e t h ylb e n zyl)b e n zyl-
a m in o]-2-(tr im eth ysilyl)a cetylen e))d icoba lt(Co-Co), 3f.
The general procedure was followed by starting from a solution
of 8.0 mmol of 4 in 5 mL of diethyl ether and 1.266 g (6.0 mmol)
of (S)-(R-methylbenzyl)benzylamine (6f). The reaction leading
to the dichloroenamine 5f was carried out for 24 h at 33 °C.
After that time, 8.25 mL (13.2 mmol, 1.6 M in hexanes) of
n-BuLi was used for the elimination/transmetalation step, and
0.91 mL (7.2 mmol) of chlorotrimethylsilane was used to trap
the lithium acetylide. After filtration and solvent removal,
1.307 g of the crude silylynamine 7f was isolated as a brown
oil.
A portion of this oil (109 mg) was dissolved in 3 mL of
pentane and the resulting mixture added to a solution of 171
mg (0.50 mmol) of Co2(CO)8 in 6 mL of pentane. After 15 min
of stirring at room temperature and column chromatography,
3f (162 mg) was obtained as a green oil (55% yield, based on
the starting amine 6f): IR (film) νmax 2060, 2010, 2000, 1570
A portion of this oil (110 mg) was dissolved in 3 mL of
pentane and the resulting mixture added to a solution of 148
mg (0.43 mmol) of Co2(CO)8 in 5 mL of pentane. After 15 min
of stirring at room temperature and column chromatography,
3c (87 mg) was isolated as a green oil (36% yield, based on
the starting amine 6c): IR (film) νmax 2100, 2060, 2020, 1600
1
cm-1; H NMR (300 MHz, CDCl3) δ 0.21 (s, 9H), 1.51 (d, J )
cm-1
;
1H NMR (300 MHz, CDCl3) δ 0.41 (s, 9H), 1.80-2.30
6.6 Hz, 3H), 4.0 (d, J ) 14 Hz, 1H), 4.35 (d, J ) 14 Hz, 1H),
4.85-4.95 (m, 1H), 6.90-7.40 (m, 10H); 13C NMR (75 MHz,
CDCl3) δ 1.3 (3CH3), 15.6 (CH3), 55.4 (CH2), 65.3 (CH), 70.1
(Cq), 127.1 (CH), 127.5 (2CH), 127.7 (2CH), 127.8 (CH), 128.2
(2CH), 128.5 (2CH), 132.6 (Cq), 137.6 (Cq), 140.4 (Cq), 200.9
(CO); MS (FAB-NBA) m/z (relative intensity) 565 (M+ - CO,
15%), 509 (M+ - 3CO, 55%), 481 (M+ - 4CO, 100%).
(m, 4H), 3.37 (br, 6H), 3.30-3.80 (m, 6H); 13C NMR (75 MHz,
CDCl3) δ 1.7 (3CH3), 27.0 (2CH2), 58.8 (2CH), 63.6 (2CH3), 70.7
(2CH2), 200.9 (CO). Absorptions due to the triple bond carbons
were not observed. MS (FAB-NBA) [m/z (relative intensity)]:
513 (M+ - CO, 10%), 485 (M+ - 2CO, 37%), 457 (M+ - 3CO,
30%), 429 (M+ - 4CO, 89%), 401 (M+ - 5CO, 100%).
Hexacar bon yl(µ-(η-1-[(()-tr a n s-2,5-bis(ben zyloxym eth -
yl)p yr r olid in o]-2-(tr im eth ysilyl)a cetylen e))d icoba lt(Co-
Co), 3d . The general procedure was followed starting from a
solution of 5.0 mmol of 4 in 3 mL of diethyl ether and 933 mg
(3.0 mmol) of (()-trans-2,5-bis(benzyloxymethyl)pyrrolidine
(6d ). The reaction leading to the dichloroenamine 5d was
carried out for 2 h at 33 °C. After that time, 4.12 mL (6.6 mmol,
1.6 M in hexanes) of n-BuLi was used for the elimination/
transmetalation step, and 0.45 mL (3.6 mmol) of chlorotri-
methylsilane was used to trap the lithium acetylide. After
filtration and solvent removal, 854 mg of the crude silylyn-
amine 7d was isolated as a brown oil.
A portion of this oil (85 mg) was dissolved in 2 mL of pentane
and the resulting mixture added to a solution of 103 mg (0.30
mmol) of Co2(CO)8 in 4 mL of pentane. After 15 min of stirring
at room temperature and column chromatography, 3d (88 mg)
was isolated as a green solid (42% yield, based on the starting
Syn th esis of Dicoba lt Hexa ca r bon yl Com p lexes of
1-Am in o-2-p h en yla cetylen es. Hexa ca r bon yl(µ-(η-1-m or -
p h olin o-2-p h en yla cetylen e))d icoba lt(Co-Co), 10a . To a
solution of 261 mg (3.0 mmol) of freshly distilled morpholine
(6a ) in 7 mL of THF, cooled to -78 °C, was added via syringe
1.87 mL (3.0 mmol, 1.6 M in hexanes) of n-BuLi. After 5 min,
a solution of 409 mg (3.0 mmol) of 1-chloro-2-phenylacetylene
(8) in 3 mL of THF was added to the mixture. The system was
then allowed to warm to room temperature, 10 mL of anhy-
drous hexane was added, and the solution was filtered through
Celite under nitrogen. Solvents were removed in vacuo, and
the residual brown oil consisting of crude 1-morpholino-2-
phenylacetylene (9a ) (759 mg) was dissolved in 3 mL of
anhydrous pentane. This solution was transferred to another
flask containing a solution of 1.02 g (3.0 mmol) of Co2(CO)8 in
4 mL of pentane. After 30 min of stirring at room temperature,
the mixture was filtered through a pad of Celite and purified
by column chromatography, eluting with hexanes, to afford
810 mg (57% yield) of 10a as a green solid: IR (film) νmax 2100,
amine 6d ): IR (film) νmax 2215, 2060, 2020, 1950, 1570 cm-1
;
1H NMR (300 MHz, CDCl3) δ 0.30 (s, 9H), 1.40-2.40 (m, 4H),
3.20-3.80 (m, 6H), 4.45 (s, 4H), 7.0-7.4 (br, 10H); 13C NMR
(75 MHz, CDCl3) δ 1.8 (3CH3), 27.2 (2CH2), 63.8 (2CH), 68.4
(2CH2), 73.4 (2CH2), 127.7 (6CH), 128.4 (4CH), 138.0 (2Cq),
200.9 (CO). Absorptions due to the triple bond carbons were
not observed. MS (FAB-NBA) [m/z (relative intensity)]: 609
(M+ - 3CO, 42%), 525 (M+ - 6CO, 100%).
2060, 2010, 1710, 1620 cm-1 1H NMR (300 MHz, CDCl3) δ
;
2.93 (t, J ) 4.8 Hz, 4H), 3.82 (t, J ) 4.8 Hz, 4H), 7.20-7.40
(m, 3H), 7.45-7.50 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 52.4
(2CH2), 66.2 (2CH2), 127.3 (CH), 128.8 (4CH), 138.8 (Cq), 200.6
(CO). Absorptions due to the triple bond carbon atoms were
not observed. MS (FAB-NBA) [m/z (relative intensity)]: 473
(M+ , 20%), 445 (M+ - CO, 100%), 417 (M+ - 2CO, 100%).
Hexa ca r bon yl(µ-(η -1-[(S)-2-(m eth oxym eth yl)p yr r oli-
d in o]-2-p h en yla cetylen e))d icoba lt(Co-Co), 10b. To a so-
lution of 250 mg (2.17 mmol) of freshly distilled (S)-2-
(methoxymethyl)pyrrolidine (6b) in 7 mL of THF, cooled to
-78 °C, was added via syringe 1.35 mL (2.17 mmol, 1.6 M in
hexanes) of n-BuLi. After 5 min, a solution of 273 mg (2.0
mmol) of 8 in 3 mL of THF was added to the mixture. The
system was then allowed to warm to room temperature, 10
mL of anhydrous hexane was added, and the solution was
filtered through Celite under nitrogen. Solvents were removed
at reduced pressure, and the residual brown oil, consisting of
1-[(S)-2-(methoxymethyl)pyrrolidino]-2-phenylacetylene (9b)
(385 mg) was dissolved in 3 mL of anhydrous pentane. This
solution was transferred to another flask containing a solution
of 684 mg (2.0 mmol) of Co2(CO)8 in 4 mL of pentane. After 30
min of stirring at room temperature, the mixture was filtered
through a pad of Celite and purified by column chromatogra-
phy, eluting with hexanes, to afford 185 mg (17% yield) of 10b
Hexa ca r bon yl(µ-(η -1-[(R,R)-2,5-d im eth ylp yr r olid in o]-
2-(tr im eth ysilyl)a cetylen e))d icoba lt(Co-Co), 3e. The gen-
eral procedure was followed starting from a solution of 8.0
mmol of 4 in 5 mL of diethyl ether and 252 mg (2.54 mmol) of
(R,R)-2,5-dimethylpyrrolidine (6e). The reaction leading to the
dichloroenamine 5e was carried out for 1 h at -10 °C. After
that time, 3.49 mL (5.58 mmol, 1.6 M in hexanes) of n-BuLi
was used for the elimination/transmetalation step, and 0.38
mL (3.04 mmol) of chlorotrimethylsilane was used to trap the
lithium acetylide. After filtration and solvent removal, 429 mg
of the crude trimethylsilylynamine 7e was isolated as a brown
oil.
A portion of this oil (98 mg) was dissolved in 2 mL of pentane
and the resulting mixture added to a solution of 171 mg (0.50
mmol) of Co2(CO)8 in 6 mL of pentane. After 15 min of stirring
at room temperature and column chromatography, 3e (192 mg)
was isolated as a green solid (69% yield, based on the starting
amine 6e): IR (film) νmax 2215, 2060, 2020, 1950, 1570 cm-1
;
1H NMR (300 MHz, CDCl3) δ 0.34 (s, 9H), 1.19 (d, J ) 6.6 Hz,

7300 J . Org. Chem., Vol. 65, No. 22, 2000
Balsells et al.
as a green solid: 1H NMR (300 MHz, CDCl3) δ 2.01 (br, 4H),
3.00 (br, 2H), 3.20-3.80 (m, 3H), 3.32 (s, 3H), 7.20-7.70 (m,
5H); 13C NMR (75 MHz, CDCl3) δ 24.1 (CH2), 28.7 (CH2), 54.6
(CH2), 58.8 (CH3), 64.0 (CH), 73.2 (CH2), 86.3 (Cq), 119.3 (Cq),
126.9 (CH), 128.5 (2CH), 129.1 (2CH), 139.7 (Cq), 200.6 (CO);
MS (FAB-NBA) m/z (relative intensity) 501 (M+ , 8%), 473 (M+
- CO, 50%), 445 (M+ - 2CO, 100%).
P a u son -Kh a n d Rea ction s of 1-(Cycloa lk yla m in o)-2-
p h en yla cetylen es. (()-(1S*,2S*,6R*,7R*)-5-P h en yl-4-m or -
p h olin otr icyclo[5.2.1.02,6]d eca -4,8-d ien -3-on e, 11a . Th er -
m a l Rea ction . To a solution of 100 mg (0.211 mmol) of
complex 10a in 2 mL of toluene was added norbornadiene (195
mg, 2.11 mmol) dissolved in toluene (3 mL), and the mixture
was heated at 95 °C for 3 h, allowed to cool to room temper-
ature, filtered through Celite, and purified by column chro-
matography (2.5% v/v triethylamine pretreated SiO2, eluting
with hexanes/diethyl ether, 91/9), to give 19 mg (29% yield) of
11a as a colorless oil.
(m, 1H), 6.20-6.30 (m, 2H); 13C NMR (50 MHz, CDCl3) δ 41.0
(CH2), 43.7 (CH), 43.6 (CH), 43.9 (CH), 48.3 (2CH2), 52.2 (CH),
66.5 (2CH2), 135.5 (CH), 136.5 (CH), 138.4 (CH), 154.2 (Cq),
206.9 (Cq); MS (CI-NH3) m/z (relative intensity) 232 (M+ + 1,
100%); HRMS (CI, butane) calcd for C14H18NO2 [MH+] 232.1337,
found 232.1317.
(1S*,2S*,6S*,7R*)-4-[(S)-2-(Meth oxym eth yl)pyr r olidin o]-
tr icyclo[5.2.1.02,6]d eca -4,8-d ien -3-on e, 13b. Th er m a l Re-
a ction a t -22 °C. The above procedure was followed by
starting from 213 mg (0.57 mmol) of Co2(CO)8 in 5 mL of
pentane and 110 mg (0.52 mmol) of 1-[(S)-2-(methoxymethyl)-
pyrrolidino]-2-(trimethysilyl)acetylene (7b). After the desilyl-
ation, 225 mg (0.45 mmol, 87% yield) of complex 12b was
obtained as a green oil. This complex was dissolved in 5 mL
of toluene, the solution was cooled to -22 °C, and 415 mg (4.5
mmol) of norbornadiene was added to the system. After 24 h
of stirring at -22 °C, the mixture was filtered through Celite
and purified by chromatography to give 90 mg (77%) of 13b
as an oil. HPLC analysis (Nucleosil 120 C-18, 20 cm, MeOH/
H2O, 70/30, 0.5 mL/min): 27.50 min (64.6%), 29.30 min
(35.4%).
N-Oxid e-P r om oted Rea ction . A solution of 71 mg (0.15
mmol) of the complex 10a in 2 mL of dichloromethane was
cooled to -20 °C, and 106 mg (0.9 mmol) of anhydrous NMO
was added in one portion. After 10 min, 138 mg (1.5 mmol) of
norbornadiene was added, and the mixture was then allowed
to warm to 0 °C. After 3 h, the reaction mixture was filtered
through Celite and purified by column chromatography to give
7 mg (15%) of 11a : 1H NMR (300 MHz, CDCl3) δ 1.38 (s, 2H),
2.32 (d, J ) 5.8 Hz, 1H), 2.51 (s, 1H), 2.80-2.90 (m, 2H), 2.95
(d, J ) 5.0 Hz, 2H), 3.10-3.30 (m, 2H), 3.70 (quintuplet, J )
3 Hz, 4H), 6.24 (m, 2H), 7.30-7.45 (m, 3H), 7.45-7.55 (m, 2H);
13C NMR (75 MHz, CDCl3) δ 41.5 (CH2), 43.0 (CH), 43.6 (CH),
47.5 (CH), 49.6 (2CH2), 51.2 (CH), 67.2 (2CH2), 128.0 (2CH),
128.1 (2CH), 128.6 (CH), 136.2 (Cq), 137.3 (CH), 138.1 (CH),
148.4 (Cq), 152.0 (Cq), 206.5 (Cq); MS (CI-NH3) m/z (relative
intensity) 308 (M+ + 1, 100%); HRMS (CI, butane) calcd for
N-Oxid e-P r om oted Rea ction a t -30 °C. Starting from
190 mg (0.55 mmol) of Co2(CO)8 in 5 mL of pentane and 98
mg (0.464 mmol) of 7b, 172 mg (0.40 mmol, 87%) of the
desilylated complex 12b was obtained. This complex was
dissolved in 5 mL of dichloromethane, the solution was cooled
to -30 °C, and 284 mg (2.43 mmol) of anhydrous NMO and
378 mg (4.1 mmol) of norbornadiene were added to the system.
After 12 h the reaction was complete. The mixture was filtered
through Celite and purified by chromatography to give 71 mg
(68%) of 13b as an oil: HPLC analysis 27.50 min (69.4%),
29.30 min (30.6%); IR (film) νmax 1700, 1600 cm-1 1H NMR
;
(200 MHz, CDCl3, major diastereomer) δ 1.25-1.35 (m, 2H),
1.76 (br, 1H), 1.82-1.95 (m, 3H), 2.21 (m, 1H), 2.57 (br, 2H),
2.86 (s, 1H), 3.00-3.20 (m, 2H), 3.35 (s, 3H), 3.30-3.50 (m,
2H), 4.15-4.20 (m, 1H), 5.85-5.90 (m, 1H), 6.10-6.20 (m, 1H),
6.20-6.30 (m, 1H); 13C NMR (50 MHz, CDCl3, major diaste-
reomer) δ 22.9 (CH2), 28.4 (CH2), 41.1 (CH2), 43.5 (CH), 43.9
(CH), 44.1 (CH), 49.3 (CH2), 52.0 (CH), 57.2 (CH), 59.0 (CH3),
74.2 (CH2), 128.3 (CH), 136.3 (CH), 138.5 (CH), 150.2 (Cq),
205.7 (Cq); MS (CI-NH3) m/z (relative intensity) 260 (M+ + 1,
100%); HRMS (CI, butane) calcd for C16H22NO2 [MH+] 260.1650,
found 260.1605.
C
20H22NO2 [MH+] 308.1651, found 308.1674.
(1S*,2S*,6R*,7R*)-5-P h en yl-4-[(S)-2-(m eth oxym eth yl)-
p yr r olid in o]tr icyclo[5. 2.1.02,6]d eca -4,8-d ien -3-on e, 11b.
The procedure described for the preparation of 11a was
followed starting from 170 mg (0.339 mmol) of complex 10b
in 2.5 mL of toluene and 312 mg (3.4 mmol) of norbornadiene
in toluene (2.5 mL) The reaction was conducted at 70 °C for 5
h and led to 11b (11 mg) as a 4:1 mixture of diastereomers in
9% yield. The major one could be separated by column
chromatography as an oil. 11b (major diastereomer: 1H NMR
(200 MHz, CDCl3) δ 1.20-2.10 (m, 9H), 2.23 (m, 1H), 2.70-
3.40 (m, 5H), 3.24 (s, 3H), 6.10-6.30 (m, 2H), 7.20-7.40 (m,
3H), 7.50-7.60 (m, 2H).
(1R *,2S *,6S *,7S *)-4-[(S )-2-(Me t h oxym e t h yl)p yr r oli-
d in o]tr icyclo[5.2.1.02,6]-4-d ecen -3-on e, 14b. Th er m a l Re-
a ction a t Room Tem p er a tu r e. The general procedure was
followed starting from 87 mg (0.26 mmol) of Co2(CO)8 in 5 mL
of pentane and 45 mg (0.21 mmol) of 7b. After the desilylation,
80 mg (0.19 mmol, 88%) of complex 12b was obtained as a
green oil. This complex was dissolved in 4 mL of toluene, and
188 mg (2.0 mmol) of norbornene was added to the system.
After 30 min of stirring at room temperature, the mixture was
filtered through Celite and purified by chromatography to give
11 mg (22%) of 14b as an oil. HPLC analysis (Nucleosil 120
C-18, 20 cm. MeOH/H2O, 70/30, 0.5 mL/min): 34.66 min
(66.6%); 36.52 min (33.4%).
Gen er a l P r oced u r e for th e P a u son -Kh a n d Rea ction s
ofTer m in al Yn am in es.(()-(1S*,2S*,6S*,7R*)-4-Mor ph olin o-
tr icyclo[5.2.1.02,6]d eca -4,8-d ien -3-on e, 13a . To a solution of
410 mg (1.2 mmol) of Co2(CO)8 in 5 mL of pentane was added
at room temperature 187 mg (1.0 mmol) of 1-morpholino-2-
(trimethysilyl)acetylene (7a ). Gas evolution and development
of green color in the solution were observed. After 10 min, the
solvent was removed by passing a CO stream over the solution,
and 400 mg (2.9 mmol) of potassium carbonate and 5 mL of
methanol were added to the system. After 30 min of vigorous
stirring, 5 mL of pentane was added. Stirring was continued
for 2 min, the phases were allowed to separate, and the
pentane one was transferred, via cannula and under CO
pressure, to another flask. This extraction operation was
repeated 3-4 times, until the pentane phase was colorless.
Pentane was removed by passing a nitrogen stream over the
solution, and the resulting green oil (353 mg, 0.89 mmol, 89%),
consisting of the desilylated dicobalt hexacarbonyl complex
12a , was dissolved in 5 mL of toluene. Norbornadiene (920
mg, 10 mmol) was added dropwise at room temperature. When
the addition was complete, the green color had disappeared
and no 12a could be detected by TLC. The mixture was filtered
through a pad of Celite and purified by chromatography (2.5%
v/v triethylamine pretreated SiO2, eluting with hexanes/diethyl
ether, 91/9) to afford 160 mg (78% yield) of 13a as an oil: IR
(film) νmax 1705, 1610 cm-1; 1H NMR (200 MHz, CDCl3) δ 1.20-
1.40 (m, 2H), 2.22 (d, J ) 7.5 Hz, 1H), 2.60 (br, 2H), 2.90 (br,
1H), 2.95-3.25 (m, 4H), 3.78 (t, J ) 7.2 Hz, 4H), 6.15-6.20
N-Oxid e-P r om oted Rea ction a t -22 °C. If one starts
from 183 mg (0.53 mmol) of Co2(CO)8 in 5 mL of pentane and
94 mg (0.445 mmol) of 7b, 161 mg (0.378 mmol, 85%) of the
desilylated complex 12b was obtained. This complex was
dissolved in 5 mL of dichloromethane, the solution was cooled
to -22 °C, and 266 mg (2.26 mmol) of anhydrous NMO and
357 mg (3.8 mmol) of norbornene were added to the system.
After 12 h at that temperature, the reaction was complete.
The mixture was filtered through Celite and purified by
column chromatography to give 22 mg (22%) of 14b as a
colorless oil. HPLC analysis: 34.66 min (70.7%); 36.52 min
1
(29.3%). IR (film): νmax 1700, 1610 cm-1. H NMR (300 MHz,
CDCl3, major diastereomer): δ 0.85-0.95 (m, 1H), 1.05-1.35
(m, 3H), 1.40-1.70 (m, 3H), 1.75-2.00 (m, 3H), 2.05 (br, 1H),
2.12 (d, J ) 5 Hz, 1H), 2.35 (br, 1H), 2.50 (br, 1H), 2.95-3.20
(m, 2H), 3.33 (s, 3H), 3.30-3.50 (m, 2H), 4.05-4.20 (m, 1H),
5.80 (d, J ) 2.7 Hz, 1H). 13C NMR (75 MHz, CDCl3, major
diastereomer): δ 22.9 (CH2), 28.4 (CH2), 28.4 (CH2), 28.9 (CH2),
30.8 (CH2), 39.0 (CH), 39.3 (CH), 45.3 (CH), 49.4 (CH2), 54.0

Low-Energy Pathway for Pauson-Khand Reactions
J . Org. Chem., Vol. 65, No. 22, 2000 7301
(CH), 57.2 (CH), 58.8 (CH3), 74.2 (CH2), 128.3 (CH), 149.5 (Cq),
HRMS (CI, butane): calcd for C18H28NO3 [MH+] 306.2069,
found 306.2022.
206.0 (Cq). MS (CI-NH3) [m/z (relative intensity)]: 262 (M+
+
1, 24%). HRMS (CI, butane): calcd for C16H24NO2 [MH+]
262.1807, found 262.1778.
(()-(1S*,2S*,6S*,7R*)-4-[tr a n s-2,5-Bis(ben zyloxym eth -
yl)pyr r olidin o]tr icycl o[5.2.1.02,6]deca-4,8-dien -3-on e, 13d.
Th er m a l r ea ction a t -20 °C. The general procedure was
followed starting from 131 mg (0.384 mmol) of Co2(CO)8 in 5
mL of pentane and 130 mg (0.32 mmol) of (()-1-[trans-2,5-
bis(benzyloxymethyl)pyrrolidino]-2-(trimethysilyl)acetylene, 7d.
After desilylation, 100 mg (0.161 mmol, 50%) of complex 12d
was obtained as a green oil. This complex was dissolved in 5
mL of toluene, the mixture was cooled to -20 °C, and 160 mg
(1.7 mmol) of norbornadiene was added to the system. After
12 h of stirring at -20 °C, the mixture was filtered through a
short pad of Celite and purified by column chromatography
to afford 24 mg (32%) of 13d as an oil. HPLC analysis
(Nucleosil 120 C-18, 20 cm, MeOH/H2O, 70/30, 1.0 mL/min):
109.6 min (87.4%); 116.6 min (12.6%).
(1S*,2S*,6S*,7R*)-4-[(2R,5R)-2,5-Bis(m eth oxym eth yl)-
p yr r olid in o]tr icyclo[ 5.2.1.02,6]d eca -4,8-d ien -3-on e, 13c.
Th er m a l Rea ction a t -35 °C. The general procedure was
followed starting from 203 mg (0.596 mmol) of Co2(CO)8 in 6
mL of pentane and 152 mg (0.596 mmol) of 1-[(2R,5R)-2,5-bis-
(methoxymethyl)pyrrolidino]-2-(trimethysilyl)acetylene (7c).
After desilylation, 176 mg (0.375 mmol, 63%) of complex 12c
was obtained as a green oil. This complex was dissolved in 5
mL of toluene, the mixture was cooled to -35 °C, and 350 mg
(3.8 mmol) of norbornadiene was added to the system. After 3
days of stirring at -35 °C, the mixture was filtered through
Celite and purified by column chromatography to give 25 mg
(22%) of 13c as an oil. HPLC analysis (Nucleosil 120 C-18, 20
cm. MeOH/H2O, 70/30, 0.5 mL/min): 22.74 min (88.8%); 24.47
min (11.2%).
N-Oxid e-P r om oted Rea ction a t -35 °C. Starting from
227 mg (0.66 mmol) of Co2(CO)8 in 5 mL of pentane and 170
mg (0.66 mmol) of 7c, 200 mg (0.42 mmol, 63%) of the
desilylated complex 12c was obtained. This complex was
dissolved in 5 mL of dichloromethane, the solution was cooled
to -35 °C, and 295 mg (2.52 mmol) of anhydrous NMO and
386 mg (4.2 mmol) of norbornadiene were added to the system.
After 5 h of stirring at that temperature, the reaction was
complete. The mixture was filtered through Celite and purified
by column chromatography to give 23 mg (18%) of 13c as an
oil. HPLC analysis: 22.74 min (94.0%); 24.47 min (6.0%). IR
(film): νmax 1705, 1605 cm-1. 1H NMR (300 MHz, CDCl3, major
diastereomer): δ 0.85-0.95 (m. 1H), 1.20-1.40 (m, 2H), 1.70-
2.20 (m, 4H), 2.50-2.65 (m, 2H), 2.87-2.90 (m, 1H), 3.03 (dd,
J ) 9.6, 7.8 Hz, 2H), 3.20-3.40 (m, 2H), 3.28 (s, 6H), 4.18 (br,
2H), 6.00 (d, J ) 3.0 Hz, 1H), 6.15-6.20 (m, 1H), 6.23-6.30
(m, 1H). 13C NMR (75 MHz, CDCl3, major diastereomer): δ
26.1 (2CH2), 41.1 (CH2), 43.7 (CH), 43.9 (CH), 44.5 (CH), 51.5
(CH), 57.4 (2CH), 59.0 (2CH3), 73.1 (2CH2), 130.4 (CH), 136.2
(CH), 138.4 (CH), 148.8 (Cq), 205.9 (Cq). MS (CI-NH3) [m/z
(relative intensity)]: 304 (M+ + 1, 100%). HRMS (CI, bu-
tane): calcd for C18H26NO3 [MH+] 304.1912, found 304.1907.
(1R*,2S*,6S*,7S*)-4-[(2R,5R)-2,5-Bis(m eth oxym eth yl)-
p yr r olid in o]tr icyclo[ 5.2.1.02,6]d ec-4-en -3-on e, 14c. Th er -
m a l Rea ction a t -21 °C. The general procedure was followed
starting from 201 mg (0.588 mmol) of Co2(CO)8 in 6 mL of
pentane and 150 mg (0.588 mmol) of 7c. After desilylation,
160 mg (0.34 mmol, 58%) of complex 12c was obtained as a
green oil. This complex was dissolved in 5 mL of toluene, the
mixture was cooled to -21 °C, and 320 mg (3.4 mmol) of
norbornene was added to the system. After 6 days of stirring
at -21 °C, the mixture was filtered through Celite and purified
by column chromatography to give 21 mg (20%) of 14c as a
colorless oil. HPLC analysis (Nucleosil 120 C-18, 20 cm, MeOH/
H2O, 70/30, 0.5 mL/min): 26.65 min (89.5%); 28.55 min
(10.5%).
N-Oxid e-P r om oted Rea ction a t -20 °C. If one starts
from 131 mg (0.384 mmol) of Co2(CO)8 in 5 mL of pentane and
130 mg (0.32 mmol) of 7d , 100 mg (0.161 mmol, 50%) of
desilylated complex 12d was obtained. This complex was
dissolved in 5 mL of dichloromethane, the solution was cooled
to -20 °C, and 115 mg (0.982 mmol) of anhydrous NMO and
160 mg (1.7 mmol) of norbornadiene were added to the system.
After 4 h of stirring at that temperature, the reaction was
complete. The mixture was filtered through Celite and purified
by column chromatography to give 25 mg (34%) of 13d . HPLC
analysis: 109.6 min (88.6%); 116.6 min (11.4%). IR (film): νmax
1
1680, 1580 cm-1. H NMR (300 MHz, CDCl3, major diastere-
omer): δ 0.80-0.95 (m, 1H), 1.05-1.15 (m, 1H), 1.20-1.30 (m,
1H), 1.80-2.10 (m, 4H), 2.47 (br, 2H), 2.82 (s, 1H), 3.15 (dd, J
) 6.4, 5.0 Hz, 2H), 3.34 (dd, J ) 6.4, 2.2 Hz, 2H), 4.20 (br,
2H), 4.40-4.50 (m, 4H), 5.88 (d, J ) 3.3 Hz, 1H), 6.14-6.20
(m, 1H), 6.21-6.25 (m, 1H), 7.20-7.40 (m, 10H). 13C NMR (75
MHz, CDCl3, major diastereomer): δ 26.5 (2CH2), 41.1 (CH2),
43.6 (CH), 44.2 (CH), 44. 5 (CH), 51.5 (CH), 57.7 (2CH), 70.7
(2CH2), 73.1 (2CH2), 127.5 (2CH), 127.6 (4CH), 128.3 (4CH),
130. 7 (CH), 136.2 (CH), 138.4 (CH), 138.4 (Cq), 148.9 (2Cq),
205.9 (Cq). MS (CI-NH3) [m/z (relative intensity)]: 456 (M+
+
1, 100%). HRMS (CI, butane): calcd for C30H34NO3 [MH+]
456.2539, found 456.2475.
(()-(1R*,2S*,6S*,7S*)-4-[tr a n s-2,5-Bis(ben zyloxym eth -
yl)pyr r olidin o]tr icycl o[5.2.1.02,6]dec-4-en -3-on e, 14d. Th er -
m a l Rea ction a t -21 °C. The general procedure was followed
by starting from 141 mg (0.41 mmol) of Co2(CO)8 in 5 mL of
pentane and 170 mg (0.41 mmol) of 7d . After desilylation, 130
mg (0.21 mmol, 51%) of complex 12d was obtained as a green
oil. This complex was dissolved in 5 mL of toluene, the mixture
was cooled to -21 °C and 197 mg (2.1 mmol) of norbornene
was added to the system. After 7 d of stirring at -21 °C, the
mixture was filtered through a pad of Celite and purified by
column chromatography to give 47 mg (49%) of 14d as a
colorless oil. HPLC analysis (Nucleosil 120 C-18, 20 cm, MeOH/
H2O, 70/30, 1.0 mL/min): 121.5 min (90.1%); 128.5 min (9.9%).
N-Oxid e P r om oted Rea ction a t -21 °C. If one starts
from 159 mg (0.466 mmol) of Co2(CO)8 in 5 mL of pentane and
190 mg (0.466 mmol) of 7d , 143 mg (0.23 mmol, 49%) of the
desilylated complex was obtained. This complex was dissolved
in 6 mL of dichloromethane, the solution was cooled to -21
°C, and 161 mg (1.38 mmol) of anhydrous NMO and 216 mg
(2.3 mmol) of norbornene were added to the system. After 6 h
of stirring at that temperature, the reaction was complete. The
mixture was filtered through a pad of Celite and purified by
column chromatography to give 47 mg (45%) of 14d . HPLC
analysis: 121.5 min (87.2%); 128.5 (12.8%). 1H NMR (300
MHz, CDCl3): δ 0.80-1.00 (m, 2H), 1.10-1.30 (m, 2H), 1.50-
1.60 (m, 2H), 1.75-2.10 (m, 6H), 2.10-2.45 (m, 2H), 3.12 (dd,
J ) 9.3, 7.5 Hz, 2H), 3.35 (dd, J ) 7.5, 3.6 Hz, 2H), 4.20 (br,
2H), 4.40-4.50 (m, 4H), 5.85 (d, J ) 4.0, 1H [major]), 7.20-
7.40 (m, 10H). 13C NMR (75 MHz, CDCl3, major diastere-
omer): δ 26. 5 (2CH2), 28.3 (CH2), 28.9 (CH2), 30.9 (CH2), 39.1
(CH), 39.3 (CH), 45.7 (CH), 53.6 (CH), 57.7 (2CH), 70.3 (2CH2),
73.1 (2CH2), 127.5 (2CH), 127. 6 (4CH), 128.3 (4CH), 130.5
(CH), 138.5 (Cq), 148.0 (2Cq), 206.2 (Cq). MS (CI-NH3) [m/z
N-Oxid e-P r om oted Rea ction a t -30 °C. If one starts
from 218 mg (0.639 mmol) of Co2(CO)8 in 5 mL of pentane and
163 mg (0.639 mmol) of 7c, 187 mg (0.39 mmol, 62%) of the
desilylated complex 12c was obtained. This complex was
dissolved in 5 mL of dichloromethane, the solution was cooled
to -30 °C, and 280 mg (2.39 mmol) of anhydrous NMO and
375 mg (4.0 mmol) of norbornene were added to the system.
After 3 days at that temperature, the reaction was complete.
The mixture was filtered through Celite and purified by
chromatography to afford 21 mg (17%) of 14c. HPLC analy-
sis: 26.65 min (88.3%); 28.55 min (11.7%). IR (film): νmax 1705,
1
1605 cm-1. H NMR (300 MHz, CDCl3, major diastereomer):
δ 0.85-1.35 (m, 4H), 1.50-1.70 (m, 2H), 1.80-2.15 (m, 6H),
2.25-2.40 (m, 1H), 2.45-2.55 (m, 1H), 3.03 (dd, J ) 9.3, 7.8
Hz, 2H), 3.20-3.40 (m, 2H), 3.29 (s, 6H), 4.1 (m, 2H), 5.95 (d,
J ) 4.0 Hz, 1H [major]). 13C NMR (75 MHz, CDCl3, major
diastereomer): δ 26.1 (2CH2), 28.3 (CH2), 28.9 (CH2), 30.9
(CH2), 39.1 (CH), 39.4 (CH), 45.6 (CH), 53.6 (CH), 57.5 (2CH),
59.0 (2CH3), 73.0 (2CH2), 130.3 (CH), 148.0 (Cq), 206.2 (Cq).
MS (CI-NH3) [m/z (relative intensity)]: 306 (M+ + 1, 100%).

7302 J . Org. Chem., Vol. 65, No. 22, 2000
Balsells et al.
(relative intensity)]: 458 (M+ + 1, 100%). HRMS (CI, bu-
procedure for the preparation of (2R,5R)-2,5-bis(methoxy-
methyl)pyrrolidine. Helpful discussions with Prof. S.
Alvarez and Dr. E. Ruiz, as well as suggestions by one
of the reviewers, are also acknowledged.
tane): calcd for C30H36NO3 [MH+] 458.2695, found 458.2714.
Ack n ow led gm en t. Financial support from the DGI-
CYT (Grant PB98-1246) and from the CIRIT (Grant
1998SGR-00005) is gratefully acknowledged. DFT cal-
culations were performed using an IBM SP-2 computer
at the “Centre de Supercomputacio´ de Catalunya”. J .B.
thanks the CIRIT for a fellowship. We are indebted to
Prof. L. Ghosez for providing us with the experimental
Su p p or tin g In for m a tion Ava ila ble: 13C NMR spectra of
compounds 3a -f, 10a ,b, 11a , 13a -d , and 14b-d . This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O000278+