Practical cobalt carbonyl catalysis in the thermal Pauson-Khand reaction: Efficiency enhancement using Lewis bases

Article abstract of DOI:10.1021/jo0057708

In this report we have shown that the commercially available C_O2(CO)₈ and C_O4(CO)₁₂, and enyne-C_O2(CO)₆ complexes, are sufficiently effective in catalyzing the Pauson - Khand reaction under

Full text of DOI:10.1021/jo0057708

3004
J . Org. Chem. 2001, 66, 3004-3020
P r a ctica l Coba lt Ca r bon yl Ca ta lysis in th e Th er m a l
P a u son -Kh a n d Rea ction : Efficien cy En h a n cem en t Usin g Lew is
Ba ses
Marie E. Krafft,* Llorente V. R. Bon˜aga, and Chitaru Hirosawa
Department of Chemistry, The Florida State University, Tallahassee, Florida 32306-4390
mek@chem.fsu.edu
Received December 14, 2000
In this report we have shown that the commercially available Co2(CO)8 and Co4(CO)12, and enyne-
Co2(CO)6 complexes, are sufficiently effective in catalyzing the Pauson-Khand reaction under one
atmosphere of CO pressure. It was further demonstrated that the efficiencies of these cyclization
protocols could be enhanced by the presence of cyclohexylamine. These procedures have also
rendered more practical and highly convenient alternatives for the catalytic Pauson-Khand reaction.
Most importantly, we have dispelled the common belief that Co4(CO)12 is inactive in the Pauson-
Khand reaction under one atmosphere of carbon monoxide. Of mechanistic importance is that these
studies have also shown that the probable formation of Co4(CO)12 is not necessarily a dead end
pathway in the Co2(CO)8-catalyzed Pauson-Khand reaction. It is also of interest that substoichio-
metric amounts of Co2(CO)8, in DME and in the presence of cyclohexylamine, are sufficient for the
cyclocarbonylation of enynes under a nitrogen atmosphere. Our findings have provided more
practical protocols for the Pauson-Khand reaction using catalytic amounts of cobalt carbonyl
complexes and a better understanding of the influence of Lewis bases on their efficiency. These
reports on the activity of Co4(CO)12 are anticipated to develop into a convenient and practical
alternative for Co2(CO)8 catalysis.
In tr od u ction
port,12 and metallic cobalt on either mesoporous silica,13
charcoal, graphite, or mesoporous carbon,14 have been
developed as heterogeneous catalytic systems. Interest-
The application of transition metal complexes in or-
ganic transformations has rendered a powerful means
for the expeditious construction of complex cyclic struc-
tures from simple and readily available starting materi-
als, in particular, when catalysis is realized in these
reactions.1 The Pauson-Khand reaction, the [2 + 2 + 1]
cyclization of an alkene, an alkyne, and CO to furnish a
cyclopentenone framework, is no exception to this.2 When
it was first reported by Pauson and co-workers, it
involved reaction of alkenes with dicobalthexacarbonyl-
complexed alkynes, which were preformed and isolated
from the reaction of alkynes with a stoichiometric amount
of Co2(CO)8.2a However, as the synthetic potential of this
reaction and the limitation of its stoichiometric version
were recognized, catalysis in this reaction has become
the focus of research among numerous workers in this
(2) (a) Khand, I. U.; Knox, G. R.; Pauson, P. L.; Watts, W. E.;
Foreman, M. I. J . Chem. Soc., Perkin Trans. 1 1973, 977. (b) Pauson,
P. L. Tetrahedron 1985, 41, 5855. (c) Pauson, P. L. In Organometallics
in Organic Synthesis, Aspects of A Modern Interdisciplinary Field; de
Meijere, A.; tom Dieck, H., Eds.; Springer-Verlag: Berlin, 1988; p 233.
(d) Schore, N. E. Chem. Rev. 1988, 88, 1081. (e) Schore, N. E. Org.
React. 1991, 40, 1. (f) Schore, N. E. In Comprehensive Organic
Synthesis; Trost, B. M.; Fleming, I., Eds.; Pergamon Press Ltd.: Oxford,
1991; Vol. 5, p 1037. (g) Schore, N. E. In Comprehensive Organometallic
Chemistry II; Abel, E. W.; Stone, F. A.; Wilkinson, G., Eds.; Elsevier:
New York, 1995; Vol. 12, p 703. (h) Geis, O.; Schmalz, H. G. Angew.
Chem., Int. Ed. 1998, 37, 911. (i) Ingate, S. T.; Marco-Contelles, J . Org.
Prep. Proced. Int. 1998, 30, 123. (j) J eong, N. In Transition Metals in
Organic Synthesis; Beller, M.; Bolm, C., Eds.; Wiley-VCH: Weinhem,
1998; Vol. 1, p 560. (k) Chung, Y. K. Coordination Chem. Rev. 1999,
188, 297. (l) Buchwald, S. L.; Hicks, F. A. In Comprehensive Asymmetric
Catalysis; J acobsen, E. N.; Pfaltz, A.; Yamamoto, H., Eds.; Springer-
Verlag: Berlin, 1999; Vol II, p 491. (m) Brummond, K M.; Kent, J . L.
Tetrahedron 2000, 56, 3263.
(3) (a) Pagenkopf, B. L.; Livinghouse, T. J . Am. Chem. Soc. 1996,
118, 2285. (b) Belanger, D. B.; O’Mahony, D. J . R.; Livinghouse, T.
Tetrahedron Lett. 1998, 39, 7637. (c) Krafft, M. E.; Bon˜aga, L. V. R.;
Hirosawa, C. Tetrahedron Lett. 1999, 40, 9171. (d) Sugihara, T.;
Yamaguchi, M. Synlett 1998, 1384. (e) J eong, N.; Hwang, S. H.; Lee,
Y.; Chung, Y. K. J . Am. Chem. Soc. 1994, 116, 3159. (f) Hayashi, M.;
Hashimoto, Y.; Yamamoto, Y.; Usuki, J .; Saigo, K. Angew. Chem., Int.
Ed. 2000, 39, 631. (g) Hiroi, K.; Watanabe, T.; Kawagishi, R.; Abe, I.
Tetrahedron Lett. 2000, 41, 891. (h) J eong, N.; Hwang, S. H.; Lee, Y.
W.; Lim, J . S. J . Am. Chem. Soc. 1997, 119, 10549. (i) Rautenstrauch,
V.; Megard, P.; Conesa, J .; Kuster, W. Angew. Chem., Int. Ed. Engl.
1990, 29, 1413. (j) Ford, J . G.; Kerr, W. J .; Kirk, G. G.; Lindsay, D. M.;
Middlemiss, D. Synlett 2000, 1415.
3
field. Thus, protocols involving catalytic use of Co2(CO)8
and other alternative sources of cobalt carbonyls, such
as Co4(CO)12,4 Co3(CO)9(µ3-CH),5 Co4(CO)11P(OPh)3,6 Co-
(acac)2/NaBH4,7 (indenyl)Co(cod),8 CoBr2/Zn/t-BuOH,9 and
alkyne-Co2(CO)6 complex/Et3SiH10 have emerged (Scheme
1). Carbonyl complexes of Ti, Ru, Rh, and Ir have likewise
been reported to catalyze the analogous structural trans-
formation of enynes.11 Most recently, catalysis in this
reaction has also been successful under heterogeneous
conditions. Cobalt carbonyl complexes on polymer sup-
(4) (a) Kim, J . W.; Chung, Y. K. Synthesis 1998, 142. (b) Krafft, M.
E.; Bon˜aga, L. V. R. Angew. Chem., Int. Ed. 2000, 39, 3676.
(5) Sugihara, T.; Yamaguchi, M. J . Am. Chem. Soc. 1998, 120, 10782.
(6) J eong, N.; Hwang, S. H. Angew. Chem., Int. Ed. 2000, 39, 636.
(7) Lee, N. Y.; Chung, Y. K. Tetrahedron Lett. 1996, 37, 3145.
(8) Lee, B. Y.; Chung, Y. K.; J eong, N.; Lee, Y.; Hwang, S. H. J .
Am. Chem. Soc. 1994, 116, 8793.
* To whom correspondence should be addressed. Fax 850-644-8281.
(1) (a) J acobsen, E. N.; Pfaltz, A.; Yamamoto, H., Eds. Comprehen-
sive Asymmetric Catalysis; Springer-Verlag: Berlin, 1999; Vols. 1 and
2. (b) Beller, M.; Bolm, C., Eds. Transition Metals in Organic Synthesis;
Wiley-VCH: Weinhem, 1998; Vols. 1 and 2. (c) Fruhauf, H.-W. Chem.
Rev. 1997, 97, 523. (d) Ojima, I.; Tzamarioudaki, M.; Li, Z.; Donovan,
R. J . Chem. Rev. 1996, 96, 635.
(9) Rajesh, T.; Periasamy, M. Tetrahedron Lett. 1998, 39, 117.
10.1021/jo0057708 CCC: $20.00 © 2001 American Chemical Society
Published on Web 04/11/2001

Catalysis in Thermal Pauson-Khand Reaction
J . Org. Chem., Vol. 66, No. 9, 2001 3005
Sch em e 1. Coba lt Ca r bon yl Ca ta lysis in th e
and other known promoters for the Pauson-Khand
reaction at ambient temperature, e.g., amine N-oxides.
Cyclohexylamine was also shown by Livinghouse to
improve the yields of thermal Pauson-Khand reactions
with an alkyne-Co2(CO)6/Et3SiH system as a catalyst
precursor under a CO atmosphere.10
P a u son -Kh a n d Rea ction
This paper presents a full account of our studies on
the catalytic Pauson-Khand reaction under mild condi-
tions and the effect of Lewis bases in the catalysis of the
reaction. This has led to the development of highly
practical and convenient catalytic protocols (one atmo-
sphere of CO and mild temperatures) in the Pauson-
Khand reaction using cobalt carbonyl complexes, such as
Co2(CO)8, enyne-Co2(CO)6 complexes, and Co4(CO)12. It
further describes the observed efficiency enhancement in
these reactions brought about by use of cyclohexylamine,
a hard Lewis base, as an additive. Last, it also accounts
our observation that efficient cyclizations could be achieved
using substoichiometric amounts of Co2(CO)8 under a
nitrogen atmosphere, interestingly, only in the presence
of an amine.
ingly, among these multitude of protocols available for
the Pauson-Khand cyclization, Co2(CO)8 continues to be
the metal complex of choice for the reaction.
Employment of high operating temperature and CO
pressure,3d,e,h,i ultraviolet light,3a high-intensity ultra-
sound,3j supercritical fluids (as solvents),3g,6 and addi-
tives3b-f have been found to enhance Co2(CO)8 catalysis.
Additives that have been shown to be beneficial and
effective in the catalytic and stoichiometric Pauson-
Khand reactions are typically Lewis bases, which pre-
sumably serve as promoters or co-ligands for the cobalt
catalyst. Soft Lewis bases, such as phosphines,3g,15
phosphites,3e phosphine oxides,15 sulfides,16 and phos-
phane sulfides3f are known. Hard Lewis bases, such as
amines,3c,18 water,3d sulfoxides,17 and ethers3d are likewise
documented. Under these reaction conditions, an im-
provement in the yield and rate of the reaction were
generally observed, although their mode of action re-
mains speculative at this point.
Cyclohexylamine as an additive in the Pauson-Khand
reaction was introduced by Sugihara wherein a signifi-
cant increase in the efficiency and rate of stoichiometric
thermal cycloadditions was observed.18 It was proposed
by the authors that the labilizing ability of the amine, a
“hard” ligand, induced a more facile decarbonylation of
the alkyne-Co2(CO)6 complex. Coordination of the reac-
tive alkene onto the metal is consequently facilitated,
thereby speeding up the cycloaddition process. Other
amines, (R-methylbenzylamine, N,N,N′,N′-tetramethyl-
ethylenediamine) or alternatively, amides (N,N-dimeth-
ylformamide) have also been used by Periasamy to induce
the stoichiometric Pauson-Khand reaction of in situ
generated alkyne-Co2(CO)6 complexes at room temper-
ature.9 These latter methods for the promotion of cy-
cloadditions were inferior to the thermal counterpart19
Resu lts a n d Discu ssion
A. Octa ca r bon yld icoba lt Ca ta lysis. Although the
utility of less than an equivalent of Co2(CO)8 for the
Pauson-Khand reaction was first shown by Pauson,2a
efficient catalysis in the reaction was only achieved later
by Rautenstrauch.3i In their synthesis of a dihydrojas-
monate precursor, a high turnnover number (>220) was
realized albeit under high temperature and CO pressure
(150 °C, 310-360 bar total pressure). As a consequence,
catalytic protocols involving Co2(CO)8 and other alterna-
tive sources of cobalt carbonyls that have evolved were
all performed under similarly rigorous conditions (80-
150 °C, 3-40 atm CO). It was only in 1996 that the very
first practical procedure was reported, where high-
intensity visible light was used by Livinghouse to pro-
mote efficient cyclizations under much milder conditions
(50-55 °C, 1 atm CO).3a Noting that temperatures of at
least 50 °C were necessary to achieve useful reaction
rates, it was later reported from the same laboratories
that heat alone was sufficient to promote Co2(CO)8
catalysis, although at a narrow thermal window (60-70
°C).3b It is noteworthy that highly pure Co2(CO)8 was
necessary in this protocol (and in other Co2(CO)8-
catalyzed procedures) to achieve the best efficiency albeit
its purification can be difficult and impractical.3a,d,6 This
complex is commercially dispensed with 1-5% hexane
as stabilizer and is rigorously purified by either recrys-
tallization or reduced-pressure sublimation at room tem-
perature. When highly pure and hexane-free, however,
Co2(CO)8 is moderately air-sensitive and pyrophoric.6,20
We investigated the catalytic Pauson-Khand reaction
under the Livinghouse conditions, but using the com-
mercially available Co2(CO)8 and in the presence of an
additive, e.g., cyclohexylamine.21
(10) Belanger, D. B.; Livinghouse, T. Tetrahedron Lett. 1998, 39,
7641.
(11) Ti: (a) Hicks, F. A.; Kablaoui, N. M.; Buchwald, S. L. J . Am.
Chem. Soc. 1999, 121, 5881. (b) Hicks, F. A.; Buchwald, S. L. J . Am.
Chem. Soc. 1999, 121, 7026. Ru: (c) Kondo, T.; Suzuki, N.; Okada, T.;
Mitsudo, T. J . Am. Chem. Soc. 1997, 119, 6187. (d) Morimoto, T.;
Chatani, N.; Fukumoto, Y.; Murai, S. J . Org. Chem. 1997, 62, 3762.
Rh (e) Koga, Y.; Kobayashi, T.; Narasaka, K. Chem Lett. 1998, 249. (f)
J eong, N.; Lee, S.; Sung, B. S. Organometallics 1998, 17, 3642. (g)
J eong, N.; Sung, B. K.; Choi, K. Y. J . Am. Chem. Soc. 2000, 122, 6771.
Ir: (h) Shikata, T.; Takagi, K. J . Am. Chem. Soc. 2000, 122, 9852.
(12) Comely, A. C.; Gibson, S. E.; Hales, N. J . Chem. Commun. 2000,
305.
Op tim iza tion of Rea ction Con d ition s. Initial stud-
ies showed that the cyclization of an enyne could be
(13) Kim, S.-W.; Son, S. U.; Lee, S. I.; Hyeon, T.; Chung, Y. K. J .
Am. Chem. Soc. 2000, 122, 1550.
(14) Son, S. U.; Lee, S. I.; Chung, Y. K. Angew. Chem., Int. Ed. 2000,
39, 4158.
(15) Billington, D. C.; Helps, I. M.; Pauson, P. L.; Thomson, W.;
Willison, D. J . Organomet. Chem. 1988, 354, 233.
(16) Sugihara, T.; Yamada, M.; Yamaguchi, M.; Nishizawa, M.
Synlett 1999, 771.
(17) Chung, Y. K.; Lee, B. Y.; J eong, N.; Hudecek, M.; Pauson, P. L.
Organometallics 1993, 12, 220.
(19) Rajesh, T.; Periasamy, M. Tetrahedron Lett. 1999, 40, 817.
(20) Kemmitt, R. D. W.; Russell, D. R. In Comprehensive Organo-
metallic Chemistry; Abel, E. W.; Stone, F. A.; Wilkinson, G., Eds.;
Pergamon Press Ltd.: Oxford, 1982; Vol. 5, p 1.
(21) After our initial report (ref 3c), commercially available Co2(CO)8
was also found to be sufficiently reactive in the catalytic Pauson-
Khand reaction using phosphane sulfide as an additive under one
atmosphere of CO; see ref 3f.
(18) Sugihara, T.; Yamada, M.; Ban, H.; Yamaguchi, M.; Kaneko,
C. Angew. Chem., Int. Ed. Engl. 1997, 36, 2801.

3006 J . Org. Chem., Vol. 66, No. 9, 2001
Krafft et al.
Ta ble 1. Op tim iza tion Stu d ies for Co2(CO)8 Ca ta lysis
u n d er On e Atm osp h er e of CO
tion of the starting material. Similar results were also
obtained from using a fresh bottle of anhydrous DME
from Aldrich (sure seal bottle under nitrogen) (entry 4
vs 5-7). Further evaluation of the catalytic reaction in
different solvents showed lower yields of cyclized products
in THF or toluene than in DME (Table 2). Among the
enynes surveyed only enyne 1 gave the same yields in
DME and toluene (entries 1-3); a lower yield was
observed in THF (entry 4). A 1:1 mixture of DME and
toluene gave an intermediate yield and reaction time
(entry 6).
Co2(CO)8
(mol %)
CyNH2
entrya
(mol %) temp (°C) time (h) % yield
1
2
3
4
5
6
7
8
9
5
10
10
10
10
10
10
5
0
0
65
65
65
65
65
65
65
70
70
2
15
5
2.5
4.5
4
4
5
15
60
80
87
84
81
84
84
89
77
10
20
20
20
20
10
5
Scop e a n d Lim ita tion s. The reactions summarized
in Table 3 were each carried out in the presence and
absence of cyclohexylamine to evaluate the scope and
limitations of this protocol. In the examples shown, the
use of cyclohexylamine provided an enhancement in the
yields in most cases, although this does not appear to be
predictable (cf. Table 1). However, a delicate balance of
the amine and Co2(CO)8 is essential to the efficiency of
this method. Examination of the results shows that an
apparent limitation of the reaction conditions for the
catalytic Pauson-Khand reactions under one atmosphere
of CO is that enynes bearing internal alkynes and lacking
significant Thorpe-Ingold assistance (entries 16, 17, and
18-20) or are sterically encumbered (entries 13 and 14)
do not undergo efficient cyclization using 10 mol %
catalyst loadings and require higher quantities of catalyst
(30-60 mol %). It is speculated that under one atmo-
sphere of CO, there exists a competition between CO and
the alkene for coordination onto the newly generated
vacant site on the cobalt metal. CO coordination is more
favored when (a) steric interactions on the alkene or
alkyne inhibit binding, or (b) a significant conformational
mobility in the alkene tether slows down the rate of
alkene binding. Subsequently, the catalyst decomposes
over a prolonged reaction time.
10
a
Entry 4: anhydrous DME from Aldrich (sure seal bottle under
nitrogen), entries 5-7: Co2(CO)8 used each came from a different
bottle.
achieved in DME using 5-10 mol % of commercially
available Co2(CO)8 at 65-70 °C under an atmospheric
pressure of CO, either with or without cyclohexylamine
(Table 1). In contrast to most Co2(CO)8-catalyzed proto-
cols,3a,b,d,e we found that the catalytic reaction proceeded
to completion with unpurified commercially available Co2-
(CO)8,21 provided carefully base-washed glassware was
used. Essentially identical results were obtained when
three different bottles of Co2(CO)8 were employed without
purification (entries 5-7). These bottles were stored in
a laboratory freezer and had been warmed to room
temperature and then exposed to air for material trans-
fer. Thus, we found that good commercial samples of Co2-
(CO)8 that have been properly stored (not necessarily in
a drybox) were sufficiently reactive for the catalytic
process. None of the manipulations were carried out
inside a glovebox. It was also observed that inadvertent
introduction of air into the system from frequent checking
of the reaction by TLC resulted in incomplete consump-
B. Dicoba lth exa ca r bon yl-Com p lexed En yn es a s
Ca ta lyst P r ecu r sor s. Recognizing the difficulty and
Ta ble 2. Solven t Effect on Co2(CO)8 Ca ta lysis u n d er On e Atm osp h er e of COa
a
All reactions were carried out using a substrate concentration of 0.1 M in toluene with 10 mol % of Co2(CO)8 and 0 or 20 mol % of
cyclohexylamine under a CO atmosphere at 65 °C, unless stated otherwise. 65-70 °C. c 0.2 M substrate concentration, 70 °C. RSM )
Recovered Starting Material.
b

Catalysis in Thermal Pauson-Khand Reaction
J . Org. Chem., Vol. 66, No. 9, 2001 3007
Ta ble 3. Th er m a lly P r om oted Co2(CO)8-Ca ta lyzed P a u son -Kh a n d Rea ction sa
a
All reactions were carried out using a substrate concentration of 0.2 M in DME with varying amounts of Co2(CO)8 and CyNH2 under
a CO atmosphere at 70 °C. 5 mol % Co2(CO)8. c 5 mol % Co2(CO)8 and 10 mol % CyNH2. 10 mol % Co2(CO)8 and 40 mol % CyNH2.e 10
b
d
mol % Co2(CO)8 and 50 mol % CyNH2. f 15 mol % Co2(CO)8 only. Complex formed during a 2 h period. 10 mol % Co2(CO)8 and 40 mol
g
h
i
j
% CyNH2. 60 mol % Co2(CO)8 and 0 or 120 mol % CyNH2. Stoichiometric amounts of Co2(CO)8 and 0 or 2 equiv of CyNH2, RSM )
recovered starting material, NR ) no reaction.

3008 J . Org. Chem., Vol. 66, No. 9, 2001
Krafft et al.
Sch em e 2. Dicoba lth exa ca r bon yl-Com p lexed Alk yn e a n d En yn e a s Ca ta lyst P r ecu r sor s
Sch em e 3. Su r vey of Ca ta lyst P r ecu r sor s
Ta ble 4. Eva lu a tion of Ca ta lyst P r ecu r sor s
impracticability of Co2(CO)8 purification, which was
believed to be necessary for an efficient Pauson-Khand
reaction catalysis under an atmospheric pressure of CO,
an alternative reaction procedure was also provided by
Livinghouse.10 This protocol involved the use of a shelf-
stable alkyne-Co2(CO)6 complex, which serves as a
convenient surrogate for the labile Co2(CO)8. The active
catalyst was presumably generated in situ from the
reduction of the premade and purified initial alkyne-
Co2(CO)6 complex with Et3SiH (Scheme 2). Since the
feasibility of efficient catalytic cycles under mild labora-
tory conditions using the alkyne-Co2(CO)6 complex-Et3-
SiH system and Co2(CO)8 itself had been demonstrated,
it seemed possible that a suitably substituted enyne-
Co2(CO)6 complex might exhibit the same reactivity.
Under a CO atmosphere, the Pauson-Khand reaction of
a dicobalthexacarbonyl-complexed enyne could likewise
generate the appropriate catalyst, thereby making the
reduction step unnecessary (Scheme 2). This section
describes the preparation and utility of new catalyst
precursors (enyne-Co2(CO)6 complexes), which obviate
the need for the additional reduction step.22
Design of Ca ta lyst P r ecu r sor s. Several require-
ments were envisioned in the design of a suitable catalyst
precursor. First, the enyne complex needed to be suf-
ficiently reactive to undergo cycloaddition and liberate
the catalyst at a reasonable rate upon heating. Com-
plexes of enynes bearing terminal alkynes or having
Thorpe-Ingold assistance generally cyclize at a sufficient
rate. Second, the cycloaddition product from the catalyst
precursor must differ in polarity from the desired product
to eliminate any separation problems after the reaction.
Finally, the catalyst precursor must be shelf-stable,
entry
catalyst
temp (°C)
time (h)
% yield
1
2
3
4
5
Co2(CO)8
65
70
70
70
70
15
2
5
1
1
80
78
79a
75
92
32
33
35
37
a
Percent yield calculation based on expected product from the
catalyst plus the substrate.
preferably crystalline, and easy to purify. Although it
may not always be practical, a catalytic amount of the
dicobalthexacarbonyl complex of the actual substrate of
interest could also be used.
To demonstrate the generality of using enyne com-
plexes in initiating the catalytic cycle, the enyne-Co2-
(CO)6 complexes depicted in Scheme 3 were chosen as
representative catalyst precursors. Comparative Pau-
son-Khand reactions of enyne 1 using these enyne-Co2-
(CO)6 complexes are listed in Table 4, which show the
effectiveness of these catalyst precursors in initiating the
cycloaddition. While catalyst precursor 33 demonstrates
the use of the substrate itself as the catalyst precursor,
enyne complex 32 typifies a precatalyst which generates
a cycloadduct (enone 34) that is polar enough to be
readily separated from the desired cyclization products.
Enone 36, formed from precatalyst 35, can be either
washed out with base or removed by filtration of the
reaction mixture through a short plug of silica gel

Catalysis in Thermal Pauson-Khand Reaction
J . Org. Chem., Vol. 66, No. 9, 2001 3009
Ta ble 5. Op tim iza tion Stu d ies for Th er m a l
Cycloa d d ition s Ca ta lyzed by a n En yn e-Co2(CO)6
Com p lexa
ter was also isolated by Pauson from the thermal cy-
clizations of (acetylene)Co2(CO)6 complexes with strained
alkenes in isooctane under a nitrogen atmosphere.2a
Isolation of (arene)Co4(CO)9 complexes under thermal
Pauson-Khand reaction conditions in aromatic solvents
also indicated the possible generation of this cluster
under these cyclization conditions.25 In effect, develop-
ment of methods involving Co2(CO)8 catalysis has been
based on preserving the catalytic cobalt species and
preventing the formation of inactive cobalt species, such
as Co4(CO)12.
Reactions demonstrating effective Co4(CO)12 catalysis
in the Pauson-Khand reaction were only achieved at
high temperature and pressure (10 atm CO, 150 °C)4a or
in a supercritical fluid as a solvent (5 atm CO, 110 atm
supercritical ethylene, 85 °C).6 It has been believed that
under these conditions, Co4(CO)12 is disproportionated
into Co2(CO)8 and is also prevented from forming.4a The
analogous methylidenyne nonacarbonyl cluster, Co3(CO)9-
(µ3-CH),5 and the phosphine-substituted cobalt cluster,
Co4(CO)11P(OPh)3,6 have been disclosed to serve as
catalyst precursors for these cyclizations. Unfortunately,
these air stable clusters are not readily available unlike
the parent cluster, Co4(CO)12, and the reported protocols
employing them involve elevated temperatures and pres-
sures.5,6
catalyst
precursor
(mol %)
% yield
CyNH2
entry
(mol %) temp (°C) time (h)
1
2
1
2
3
4
5
5
10
10
10
10
10
0
20
0
65
65
65
70
70
7
6.5
6
4.5
4
73
15
9
-
-
25
63
78
70
82
20
a
Entries 3-5: 0.2 M substrate concentration.
necessary to remove the cobalt residues. In the same
manner, enone 7 from precursor 37, can be removed via
an acid wash or filtration through a silica gel plug.
Op tim iza tion of Rea ction Con d ition s. Table 5
shows the results from reactions designed to determine
the best conditions for the Pauson-Khand reaction using
enyne-Co2(CO)6 complex 32 as precatalyst. We have
chosen complex 32 as our precatalyst for the reaction
since it is crystalline and stable to be conveniently stored
in a laboratory freezer. The yield enhancement brought
about by the presence of cyclohexylamine in the Co2(CO)8-
catalyzed reactions prompted us to use the amine in these
cyclizations. Complete reactions were only achieved at
70 °C (entries 4 and 5). A lower temperature resulted
only in incomplete conversion, even with varying amounts
of the precatalyst and cyclohexylamine (entries 1-3). As
previously demonstrated, cyclohexylamine is important
for this reaction (entry 2 vs 3 and entry 4 vs 5).
In an attempt to understand the efficiency enhance-
ment provided by cyclohexylamine (vide supra) we con-
ducted Pauson-Khand cyclization studies employing the
Co4(CO)12 cluster under our reaction conditions. We
postulated that cyclohexylamine preserves the active
catalyst and induces catalyst formation via dispropor-
tionation of Co4(CO)12, which may possibly be formed
during catalytic reactions using Co2(CO)8. In fact, a well-
established equilibrium between Co2(CO)8 and Co4(CO)12
is known.24
Gen er a lity of th e P r oced u r e. The examples in Table
6 illustrate the generality of using catalyst precursor 32
for initiating the intramolecular Pauson-Khand reaction.
As was previously observed, some of the cycloadditions
proceeded in higher yields in the presence of cyclohex-
ylamine. The reasons for this yield enhancement is not
entirely clear, and the outcome does not appear to be
predictable with these examples. While the amine may
serve in several capacities during the reaction manifold,
it may be a catalyst carrier, which increases the longevity
of the intermediate complexes. Likewise, it may also
regenerate and/or preserve the active cobalt species.
C. Dod eca ca r bon yltetr a coba lt Ca ta lysis. Extant
knowledge on Co2(CO)8-catalyzed Pauson-Khand reac-
tions reveals that under mild conditions, Co4(CO)12
formation deters catalysis and is in fact considered as a
dead end pathway in this reaction.2j,3i,23 Co4(CO)12, which
is presumably generated from dimerization of “Co2(CO)n”
upon release of the cyclopentenone product is believed
to be inactive under these conditions. Thermal decom-
position of Co2(CO)8 in hexane, heptane, and toluene to
provide Co4(CO)12 is well-documented.24 This cobalt clus-
P r elim in a r y Stu d ies. We began our investigations
with the thermal cyclizations of enyne 3 using stoichio-
metric quantities of Co4(CO)12 in DME at 70 °C under a
nitrogen atmosphere (Table 7). A good yield of the
cyclopentenone was obtained from the cyclization of 3,
only when it was carried out in the presence of the amine
(entry 1 vs 2). Although the reactions were incomplete,
cyclizations using catalytic amounts of Co4(CO)12 were
still achieved in fair yields at 60 and 70 °C even under a
nitrogen atmosphere (entries 3 and 4). Incidentally,
cyclizations under an atmosphere of CO provided a better
yield (entry 6) and allowed a lower catalyst loading to
achieve complete reaction (entries 6 and 7), more so at a
higher temperature, i.e., 70 °C (entry 8). These results
demonstrated that catalytic amounts of Co4(CO)12 could
be used in conjunction with cyclohexylamine to catalyze
thermal Pauson-Khand reactions under practical reac-
tion conditions. Under these reaction conditions, no
cyclizations were evident when Mo(CO)6 and W(CO)6
were used as the metal carbonyls.
Com p a r ison of th e Coba lt Ca r bon yl-CyNH2 Ca ta -
lytic System s. An attempt was made to compare the
catalytic efficiencies of the two cobalt carbonyl-CyNH2
systems in DME (Table 8). However, it should be noted
that Co2(CO)8 and Co4(CO)12, and their corresponding
cyclohexylamine systems have been observed to behave
variably under our test solvents (vide infra). Neverthe-
less, results consistently indicate that, in DME, an
optimal molar ratio of cobalt carbonyl complex to cyclo-
hexylamine is 1:6 for Co4(CO)12 and 1:3 for Co2(CO)8
(22) Krafft, M. E.; Hirosawa, C.; Bon˜aga, L. V. R. Tetrahedron Lett.
1999, 40, 9177.
(23) Magnus, P.; Principe, L. M.; Slater. M. J . J . Org. Chem. 1987,
52, 1483.
(24) (a) Ungvary, F.; Marko, L. Inorg. Chim. Acta 1970, 4, 324. (b)
Ungvary, F.; Marko, L. J . Organomet. Chem. 1974, 71, 283. (c) Bor,
G.; Dietler, U. K.; Pino, P.; Poe, A. J . Organomet. Chem. 1978, 154,
301. (d) Bor, G.; Dietler, U. K. J . Organomet. Chem. 1980, 191, 295.
(e) Mirbach, M. F.; Saus, A.; Krings, A. M.; Mirbach, M. J . J .
Organomet. Chem. 1981, 205, 229.

3010 J . Org. Chem., Vol. 66, No. 9, 2001
Ta ble 6. P a u son -Kh a n d Rea ction Usin g a n En yn e-Co2(CO)6 Com p lex a s a Ca ta lyst P r ecu r sor a
Krafft et al.
a
All reactions were carried out using a substrate concentration of 0.2 M in DME with 10 mol % of complex 32 under a CO atmosphere
at 70 °C, unless stated otherwise. 20 mol % CyNH2 was used. c 40 mol % CyNH2 was used.
b
Ta ble 7. P r elim in a r y Resu lts on th e Co4(CO)12-Ca ta lyzed
Ta ble 8. Com p a r ison of Coba lt Ca r bon yl-CyNH2
Ca ta lytic System s in DME
P a u son -Kh a n d Rea ction
% yield
% yield
cobalt
carbonyl/CyNH2
(mol %:mol %)
Co4(CO)12
(mol %)
CyNH2
(mol %)
temp
(°C)
reaction
atmosphere
Co4(CO)12
Co2(CO)8
entry
3
6
entry
3
6
3
6
1
2
3
4
5
6
7
8
9
100
100
15
15
15
15
15
5
0
300
0
95
100
0
100
30
15
70
70
60
60
70
60
60
70
70
N2
N2
N2
N2
-
-
-
8
14
-
-
-
20
7
1
6
3
4
5
5:0
5:15
5:30
10:0
10:60
-
-
-
-
-
23
74
94
59
92
9
52
82
-
41
28
4
82
55
81
14
60
58
69
91
94
58
N2
46
CO
CO
CO
CO
observed with the Co2(CO)8-CyNH2 catalytic system,3c
good to excellent yields were obtained from enynes having
significant Thorpe-Ingold properties (entries 1-3, 5, 8),
although a lower yield was obtained from an enyne
bearing a disubstituted olefin (entry 4). With the present
catalyst system complete cyclization of enyne 5 was
achieved using only a 10/60 ratio of Co4(CO)12/CyNH2
whereas, with the Co2(CO)8-CyNH2 system, a 30/60 ratio
of Co2(CO)8/CyNH2 was necessary (cf. Table 3, entries
9-11). Similarly, enynes bearing internal alkynes and
lacking significant Thorpe-Ingold assistance (entry 9),
or which are sterically hindered (entry 10) needed a
higher catalyst loading (30 mol %) for complete reactions,
albeit still in modest yields. In our efforts to improve the
2.5
(Table 3 and Table 11, entries 4-7). Interestingly, a
molar ratio of 1:3 (alkyne-Co2(CO)6 or Co2(CO)8 complex/
additive) has been also used with cyclohexylamine,18
thiophene,3b R-methylbenzylamine,9 N,N,N′,N′-tetra-
methylethylenediamine,9 N,N-dimethylformamide,9 and
n-butylphosphane sulfide,3f although these reactions were
carried out under different reaction conditions.
Scop e of th e Co4(CO)12-CyNH2 P r otocol. We then
verified the generality of these observations in a series
of catalytic cyclizations of a variety of substrates employ-
ing the Co4(CO)12-CyNH2 system (Table 9). As was

Catalysis in Thermal Pauson-Khand Reaction
J . Org. Chem., Vol. 66, No. 9, 2001 3011
Ta ble 9. Co4(CO)12-CyNH2 a s Ca ta lyst System for a P r a ctica l Th er m a l P a u son -Kh a n d Rea ction a
a
Reactions were carried out at substrate concentrations of 0.05 M in DME using 10 mol % Co4(CO)12 and 60 mol % CyNH2 under a CO
atmosphere at 70 °C. Reactions were typically done in 13-18 h. 5 mol % Co4(CO)12, 30 mol % CyNH2. c With pyridine. In 1,2- DCE.
b
d
e In octane. f 30 mol % Co4(CO)12, 60 mol % CyNH2. TBS) tert-butyldimethylsilyl.
cyclizations depicted in entries 9 and 10, pyridine was
substituted for cyclohexylamine,26,27 but essentially iden-
tical results were obtained. Pyridine is one of the Lewis
bases known to induce disporportionation of Co2(CO)8 and
Co4(CO)12.26,28 In contrast, cyclization of enyne 12 with
pyridine as the additive was found to be inferior to
cyclohexylamine (entry 5). An intermolecular version of
the new Co4(CO)12/CyNH2-catalyzed cyclization was also
cobalt carbonyls in Pauson-Khand reactions. In the early
studies on the thermal decomposition of Co2(CO)8 (in
demonstrated by the reaction of phenylacetylene and the
toluene) it was shown by Ungvary and Marko that
reactive alkene norbornene to give the cycloadduct in 97%
coordinatively unsaturated Co2(CO)6 fragments are nec-
yield (eq 1).
essary for the formation of Co4(CO)12.24a Hence, an
We have therefore shown that efficient cycloadditions
atmosphere of CO or the presence of coordinating ligands,
of enynes could be attained using catalytic amounts of
such as cyclohexylamine would be expected to inhibit the
Co4(CO)12, with cyclohexylamine enhancing the efficiency.
formation of these fragments and consequently, the
These findings further exemplified the utility of additives,
dimerization to the tetranuclear cluster. On the contrary,
such as amines, in improving the catalytic efficiency of
it had been suggested that only at high pressures of CO
atmosphere would formation of the dinuclear cobalt
(25) (a) Khand, I. U.; Knox, G. R.; Pauson, P. L.; Watts, W. E. J .
Chem. Soc. Chem. Commun. 1971, 36. (b) Khand, I. U.; Knox, G. R.;
carbonyl be effectively favored from Co4(CO)12.3I
Ca ta lysis by Co4(CO)12 w ith ou t a n Ad d itive. Cy-
clizations of enyne 3 using Co4(CO)12, in the absence of
additives, in solvents commonly used in Pauson-Khand
reactions were examined to elucidate the efficiency of the
Pauson, P. L.; Watts, W. E. J . Chem. Soc., Perkin Trans. 1 1973, 975.
(26) Wender, I.; Sternberg, H. W.; Orchin, M. J . Am. Chem. Soc.
1952, 74, 1216.
(27) Krafft, M. E.; Bon˜aga, L. V. R. Synlett 2000, 959.
(28) Manuel, T. A. Adv. Organomet. Chem. 1965, 3, 181.

3012 J . Org. Chem., Vol. 66, No. 9, 2001
Ta ble 10. Co4(CO)12 a n d Co2(CO)8 Ca ta lyses in Differ en t Solven ts
Krafft et al.
Co4(CO)12
Co2(CO)8
% yield
% yield
turnover
numbera
turnover
numbera
entry
solvent
3
6
3
6
1
2
3
4
5
6
7
8
9
10
11
12
13
14
dimethyl sulfoxide (DMSO)
acetonitrile
dichloromethane (CH2Cl2)
1,2-dichloroethane (DCE)
93
61
47
-
-
35
-
0
6.9
0
94
76
-
0
1.7
9
68
14.3
29
-
-
26
5.0
3.7
2.4
37b
50c
tetrahydrofuran (THF)
1,2-dimethoxyethane (DME)
-
-
21
23
59b
9
37
41
59
61b
4.4
4.4
6.0
1.9
6.2
8.7
12.5
6.5
9
-
41
7.8
8.3
82b
toluene
86
24
30
-
n-hexane
n-heptane
isooctane
31
-
19
3.3
2.6
-
57c
a
b
Mol product/mol catalyst. 10 mol %. c 20 mol %.
cycloaddition in the presence of different solvents (Table
10). Although we intended to confirm its lack of reactivity
under our reaction conditions, we discovered otherwise
that Co4(CO)12 catalyzes the cycloaddition in a number
of solvents under normal laboratory conditions. The
highest catalytic efficiency was observed in either 1,2-
DCE and isooctane. Interestingly, Pauson and co-workers
isolated Co4(CO)12 from stoichiometric Pauson-Khand
reactions in isooctane as the solvent.2a For comparison,
cyclization efficiencies in either 1,2-DCE and DME under
the reaction conditions described in Table 9 are compa-
rable (cf. Table 9, entries 5 and 6). However, under these
catalytic conditions, no cyclization was evident in DMSO
presumably due to the formation of inactive DMSO-
cobalt complexes. A rate-decelerating effect of DMSO was
also evident in the amine oxide-promoted stoichiometric
Pauson-Khand reaction presumably due to the strong
coordinating ability of DMSO as ligand.29 In effect, DMSO
possibly formed complexes with Co4(CO)12 or its degrada-
tion products, which were inert toward catalysis in the
Pauson-Khand reaction. In contrast, DMSO has been
used as an additive to promote Pauson-Khand reactions
implying that DMSO is beneficial to enyne-Co2(CO)6
complexes, which renders them more reactive for alkene
coordination, but is detrimental to Co2(CO)8 and Co4-
(CO)12 complexes. Co2(CO)8 exhibited highest catalytic
activity in DME, which is typically used as the solvent
went disproportionation into Co2(CO)8 or a similar cata-
lytically active cobalt species. It was reported that under
one atmosphere of CO, at 53 °C a hexane solution of Co4-
(CO)12 would be converted to a solution in which 50% of
the cobalt content is present as Co2(CO)8 (t1/2 ) 160
days).24c Although the generation of Co4(CO)12 under the
Co2(CO)8-catalyzed conditions has been only assumed, we
have discounted the assumption that Co4(CO)12 is inac-
tive toward the Pauson-Khand cyclizations under mild
conditions, such as normal pressure of CO atmosphere
and lower temperature. Thus, Co4(CO)12 can now serve
as an alternative for Co2(CO)8, which is more prone to
air oxidation, and possibly Co3(CO)9(µ3-CH)5 and Co4-
(CO)11P(OPh)3,6 that both require further preparation.
Upon exposure to air, Co4(CO)12 is known to be oxidized
to a purple Co(II) species, but this proceeds at an
appreciably slower rate than Co2(CO)8.20,30 Optimal ca-
talysis of the methylidene tricobalt nonacarbonyl cluster
was achieved in toluene only at 120 °C under 7 atm of
CO.5 It is of interest that use of Co4(CO)12 was not
reported in these studies. It is also noteworthy that
commercially available Co4(CO)12 was used without
purification and was found to be catalytically efficient.
D. P a u son -Kh a n d Rea ction s u sin g Su bstoich io-
m et r ic Am ou n t s of Co2(CO)8 u n d er a Nit r ogen
Atm osph er e. The alternative procedures described above
for the cobalt-catalyzed Pauson-Khand cycloadditions3c,4b,22
demonstrate that efficient cyclizations under an atmo-
sphere of carbon monoxide could also be achieved using
catalytic quantities of different cobalt carbonyl com-
plexes. We further observed during these studies that,
in DME and in the presence of cyclohexylamine, 1,6- and
1,7-enynes could be practically converted to bicyclic
cyclopentenones using only 35-50% of Co2(CO)8 under
an atmosphere of nitrogen. To allow for regeneration of
the active catalyst, Pauson-Khand reactions employing
less than an equivalent of Co2(CO)8 are typically carried
out under an atmosphere of carbon monoxide. An excep-
tion is in an account by Schore where a nitrogen
in cobalt-catalyzed Pauson-Khand reactions.3a-c,e,8,10,22
A
subsequent increase in yield was noted for cyclizations
in DME when higher amounts of Co2(CO)8 were used
(entries 8 vs 9), although less notably in 1,2-DCE (entries
4-6) and isooctane (entries 13 and 14). As was already
reported by Chung, Co4(CO)12 did not exhibit any cata-
lytic activity in CH2Cl2 under one atmosphere pressure
of CO and optimal catalysis was only achieved at 150 °C
and 10 atm pressure of CO.4a
The observed reactivity of Co4(CO)12 at 70 °C and one
atmosphere of CO pressure, in a number of solvents,
suggested that, under our conditions, it probably under-
(29) Krafft, M. E.; Scott, I. L.; Romero, R. H.; Feibelmann, S.; Van
Pelt, C. E. J . Am. Chem. Soc. 1993, 115, 7199.
(30) King, R, B, In Organometallic Syntheses; Eisch, J . J .; King, R.
B., Eds.; Academic Press: New York, 1965; Vol. 1, p 103.

Catalysis in Thermal Pauson-Khand Reaction
J . Org. Chem., Vol. 66, No. 9, 2001 3013
Ta ble 11. Op tim iza tion Stu d ies for th e Am in e-a ssisted
Su bstoich iom etr ic Th er m a l P a u son -Kh a n d Rea ction
u n d er a Nitr ogen Atm osp h er e
the starting enynes were completely consumed to give
the corresponding bicyclic cyclopentenones in good yields.
In some cases we found it advantageous to use 50 mol %
of Co2(CO)8.
Com p a r ison of Com m on Ad d itives for th e P a u -
son -Kh a n d Rea ction . Compared to other known ad-
ditives for the cycloaddition (vide supra) cyclohexylamine
was determined to be the most efficacious in our present
studies (Table 13). During the course of these studies,
n-butyl methyl sulfide was reported to be the best suited
additive for substrates bearing a propargylic hetero-
atom.16 Addition of 3 mol equiv of this sulfide to the
cyclization of enyne 4 yielded only 51% of the cyclized
product 7. Lower yields were likewise observed from
cyclizations of substrates 10 and 13 (60% yields). We
further examined pyridine and 1,10-phenanthroline26 and
found that these aromatic N-containing Lewis bases were
inferior to cyclohexylamine. While the monodentate
pyridine behaved much better than the bidentate 1,10-
phenanthroline, it provided variable results in the cy-
clizations of representative substrates in comparison to
cyclohexylamine (Table 12, entries 2, 4, 6, 7). Addition
of 70 mol % of 1,10-phenanthroline into the reaction of
enyne 3 gave only 16% of 6 along with 67% of recovered
3.
reaction
entry concn (M)
Co2(CO)8 CyNH2 temp time
(mol %)
(mol %) (°C)
(h)
% yield
1a
2b
3
4
5
6
7
8
9
0.20
0.20
0.20
0.05
0.05
0.05
0.05
0.01
0.10
0.20
0.05
0.05
0.05
0.05
0.05
0.05
10
10
10
30
30
30
30
30
30
35
35
30
35
30
30
35
20
20
20
0
60
90
150
90
70
70
70
70
70
70
70
70
70
70
50
60
60
70
70
60
15
15
15
15
15
15
16
15.5
15.5
16
13.5
15.5
13
1
2
16
37
40
36
21
39
72
61
38
40
25
67
86
58
60
19
78
90
10
11
12
105
105
90
105
90
13
14c
15d
16
90
35
a
b
Ultrahigh purity (UHP) Ar atmosphere. N2 atmosphere.
c DCE. Toluene.
d
Mech a n istic Stu d ies. In reactions conducted under
substoichiometric conditions, we propose that the amine
preserves the active catalytic species and enhances the
longevity of the intermediate catalytic complexes. It may
also prevent the deleterious effects of nonviable cobalt
residues formed during the reaction. With regard to the
source of CO for incorporation into the enyne moieties,
we speculate that an iterative disproportionation of cobalt
residues brought about by the amine resulted in regen-
eration of dicobalt clusters bearing five to six CO ligands.
Alternatively, CO molecules from the initial ligand
exchange reaction of Co2(CO)8 with either the alkyne or
cyclohexylamine possibly remained in solution and were
further utilized in the reformation of the active catalyst.
We further designed a series of experiments to probe
the fate of the two CO molecules liberated from the initial
alkyne-Co2(CO)6 formation (based on the accepted mech-
anism for the Pauson-Khand reaction) and its effect on
reaction efficiency. These molecules could either be mixed
with the nitrogen atmosphere or remained dissolved in
the solvent. Dissolved CO molecules could then possibly
bind to any coordinatively unsaturated cobalt species in
the reaction residues or intermediates. Co2(CO)8 and
enyne-Co2(CO)6 complexes 32 and 33 were employed as
sources of cobalt carbonyls to mediate the cyclization of
enyne 1; these results are summarized in Table 14. We
have recently shown the utility of enyne-Co2(CO)6
complexes as catalyst precursors in Pauson-Khand
reactions under a CO atmosphere.22 With catalyst pre-
cursors 32 and 33, the only source of CO molecules is
clearly the enyne-Co2(CO)6 complex, and not dissolved
CO, as is possible with Co2(CO)8. Under similar reaction
conditions, cyclizations using Co2(CO)8 showed better
efficiency than reactions promoted by these catalyst
presursors (entries 2 vs 3 and 5). These results suggest
that, under these conditions, the CO molecules remained
dissolved in the reaction system and further enhanced
the efficacy of the reaction.
atmosphere was found to be more beneficial than carbon
monoxide in the thermal cyclization of norbornadiene
with several alkynes using less than stoichiometric
amounts of Co2(CO)8.31
Op tim iza tion Stu d ies. We made several observations
during our optimization studies summarized in Table
11: (1) Essentially the same efficiency was observed in
reactions carried out under an argon atmosphere com-
pared to nitrogen. (2) High dilution, a narrow tempera-
ture range (50-60 °C) and an optimal 3:1 molar ratio of
amine relative to Co2(CO)8 were expedient for achieving
good yields of cyclized products. A narrow temperature
range (60-70 °C) was also observed by Livinghouse, in
his report on the catalytic thermal cyclizations under an
atmospheric pressure of CO.3b An optimal 3:1 ratio of
cyclohexylamine relative to enyne-Co2(CO)6 complex was
reported by Sugihara18 and Periasamy.9 The same ratio
was also used by Livinghouse when using cyclohexyl-
amine as an additive although a 6:1 ratio was employed
for reactions using thiophene.10 (3) Reactions carried out
in 1,2-dichloroethane or toluene gave inferior yields than
those in DME. 1,2-Dichloroethane was the solvent used
in the first report on the thermal stoichiometric cycliza-
tions with cyclohexylamine as an additive under an Ar
atmosphere.18 DME is typically used as a solvent in
cobalt-catalyzed Pauson-Khand reactions.3a-c,e,8,10,22 How-
ever, when catalytic cyclizations were conducted in
toluene, DME was observed to be a better additive than
cyclohexylamine.3d (4) A large excess of the cyclohexyl-
amine was observed to be detrimental to the efficiency
of the reaction.
Gen er a lity of th e Obser va tion . The scope of using
substoichiometric amounts (35-50%) of Co2(CO)8 under
a nitrogen atmosphere to promote the Pauson-Khand
cycloaddition is demonstrated in Table 12. These results
show that the presence of cyclohexylamine, three molar
equivalents relative to Co2(CO)8, is crucial to the ef-
ficiency of the present cyclization procedure. In all cases,
As is illustrated above, reactions performed in the
presence of amine were more efficient than those without
the amine (entry 1 vs 2, 4 vs 5). As expected, the absence
(31) Schore, N. E. Synth. Commun. 1979, 9, 41.

3014 J . Org. Chem., Vol. 66, No. 9, 2001
Krafft et al.
Ta ble 12. Am in e-Assisted Su bstoich iom etr ic P a u son -Kh a n d Rea ction s u n d er a Nitr ogen Atm osp h er ea
a
All reactions were carried out using a catalyst concentration of 0.02 M in DME with 35 mol % Co2(CO)8 and 105 mol % CyNH2 or
b
pyridine under a nitrogen atmosphere at 60 °C. Reactions were typically done in 14-15.5 h except for entry 1 (3 h). Determined by 300
MHz 1H NMR spectroscopy. c 70 mol % CyNH2. 30 mol % Co2(CO)8, 90 mol % CyNH2. e 50 mol % Co2(CO)8, 150 mol % CyNH2. f 140 mol
d
% pyridine.
Ta ble 13. Com p a r ison of Kn ow n Ad d itives for th e
reaction of Co2(CO)8 and cyclohexylamine (30 min reac-
tion time) at room temperature (entry 1) and at 60 °C
(entry 2) are viable toward the Pauson-Khand reaction
providing moderate yields of 6, along with recovered
starting materials. As anticipated, heating Co2(CO)8 prior
to addition of the enyne would be deleterious to the
reaction even in the presence of cyclohexylamine (entry
3). It is worth noting that a slight improvement in the
reaction efficiency was observed when Co2(CO)8 was
heated with the cyclohexylamine (entry 2 vs 3). A mixture
of Co2(CO)8, cyclohexylamine and enyne also showed
incomplete reaction although this reaction condition gave
the highest yield of the product (entry 4). These results
further confirmed that the optimal procedure involves
alkyne complexation and subsequent activation of the
enyne-Co2(CO)6 complex upon addition of cyclohexyl-
amine (entry 5).
P a u son -Kh a n d Rea ction
additive
% yield
cyclohexylamine
n-butyl methyl sulfide
thiophene
thioanisole
triphenyl phosphite
86
60
27
56
30
of the additive was compensated for by carrying out the
reaction under a CO atmosphere (entry 5 vs 6). Cycliza-
tion was further shown to be more effective in DME than
in toluene (entry 5 vs 7). For purposes of comparison,
reaction of enyne 47 from which 32 was derived using
35% of Co2(CO)8 and 105% of cyclohexylamine under an
atmosphere of nitrogen gave only 34 in 66% yield.
Likewise, cyclizations of enyne 1 using precatalyst 32
showed no decomplexed enyne 47 in the product mixture
(entries 4, 5, and 7). Furthermore, any unreacted Co2-
(CO)8 could react with cyclohexylamine to produce CO
molecules that could possibly become another source of
CO.
We have shown that a substoichiometric amount of Co2-
(CO)8 is sufficient to promote the intramolecular Pauson-
Khand reaction under nitrogen rather than a carbon
monoxide atmosphere. The amine may have acted in a
role to facilitate an iterative disproportionation of cobalt
residues forming a viable cobalt catalyst for further
cycloaddition. Presumably, it also prevented detrimental
effects of nonviable cobalt residues on the reaction. Our
experiments also suggested that the CO molecules, which
evolved from the initial complexation step remained
dissolved in the reaction system and were further used
in the reaction.
The reactivity of the cobalt species formed from the
reaction of Co2(CO)8 and cyclohexylamine was further
investigated (Table 15). Studies on the cyclization of
enyne 3 suggested that the cobalt species generated from

Catalysis in Thermal Pauson-Khand Reaction
J . Org. Chem., Vol. 66, No. 9, 2001 3015
Ta ble 14. Mech a n istic Stu d ies: F a te of CO a n d Its
Effect on Rea ction Efficien cy
catalyst is possible. The current state of the art in the
Pauson-Khand reaction methods is summarized in
Scheme 4.
In this report of our studies, we have determined that
enyne-Co2(CO)6 complexes, and the commercially avail-
able Co2(CO)8 and Co4(CO)12 are sufficiently effective in
the catalytic Pauson-Khand reaction under one atmo-
sphere of CO pressure. It was further shown that the
efficiencies of these cyclization protocols could be en-
hanced by the presence of cyclohexylamine. These pro-
cedures have also rendered more practical and highly
convenient alternatives for the catalytic Pauson-Khand
reaction. Most importantly, we have dispelled the com-
mon belief that Co4(CO)12 is inactive in the Pauson-
Khand reaction under one atmosphere of carbon monox-
ide. Of mechanistic importance is that these studies have
also demonstrated that the probable formation of Co4-
(CO)12 is not necessarily a dead end pathway in the Co2-
(CO)8-catalyzed Pauson-Khand reaction. It is also of
interest that substoichiometric amounts of Co2(CO)8, in
DME and in the presence of cyclohexylamine, are suf-
ficient for the cyclocarbonylation of enynes under a
nitrogen atmosphere.
% yield
cobalt
catalyst
CyNH2
(mol %)
entry
2
34
1
2
3
4
Co2(CO)8
Co2(CO)8
0
105
105
0
105
0
52
80
54b
22
68
83
49
-
-
-
55
50
95
22
33
32
32
32
32
5
6c
7d
105
a
Reactions were performed using a substrate concentration of
0.05 M in DME with 35 mol % of cobalt catalyst and CyNH2 under
a N2 atmosphere at 60 °C. Reactions were typically done in 2-3
b
h. Percent yield is based on 2 derived from enyne 1 plus enyne-
Co2(CO)6 complex 33. c Under a CO atmosphere. Toluene.
d
The protocols developed in our studies have been based
primarily on the efficiency enhancement brought about
by Lewis bases, which has been most pronounced and
general with cyclohexylamine. In these studies we in-
voked an amine-derived stabilization of reaction inter-
mediates, which originates from its coordination to
coordinatively unsaturated cobalt species in the reaction,
e.g., reaction intermediates and “Co2(CO)n”. Thus, the
amine serves as a catalyst carrier by prolonging its
lifetime, consequently improving the reaction efficiency
(higher turnover number). It is further noteworthy that,
for an unknown reason, molar ratios of 1:2-3 (enyne-
Co2(CO)6 complex or Co2(CO)8/cyclohexylamine) and 1:6
(Co4(CO)12/cyclohexylamine have been found to be opti-
mal under these reaction conditions. A 1:3 molar ratio
Ta ble 15. Gen er a tion of th e Active Coba lt Sp ecies
% yield
has similarly been described in several reports.9,10,18
A
entry
1
reaction conditions
3
6
delicate balance of Co2(CO)8 and cyclohexylamine was
apparently essential for the enhancement effect in reac-
tions performed under CO and N2 atmospheres and a
large excess of the amine was observed to be detrimental.
We also proposed that with the substoichiometric condi-
tions under a N2 atmosphere, cyclohexylamine effected
an iterative disproportionation of residual cobalt species,
“Co2(CO)nL8-n” (L ) CO, cyclohexylamine, or DME) to
generate viable cobalt carbonyl species. Disproportion-
ation of residual cobalt species might also be possible in
reactions using Co2(CO)8 and Co4(CO)12 under a CO
atmosphere, where regeneration of the active cobalt
carbonyl is more facile. By virtue of their Lewis basicity,
results suggest that amines facilitate the initial decar-
bonylation step creating a vacant site on the cobalt center
thereby resulting in an increased reaction rate. As a
consequence, the reaction proceeds to completion before
the catalyst decomposes. The facility of the cobalt cluster
Co4(CO)12 as a catalyst precursor suggests that it pre-
sumably disproportionated into Co2(CO)8 or a similar
catalytically active cobalt species, which could be acceler-
ated by the presence of the amine. Alternatively, it may
have formed an (alkyne)Co4(CO)10 complex upon reaction
with the alkyne and may be subsequently transformed
to the (alkyne)Co2(CO)6 complex under the Pauson-
Co2(CO)8, CyNH2, rt, 30 min;
then 3, 60 °C
23
53
2
3
Co2(CO)8, CyNH2, 60 °C, 30 min;
then 3, 60 °C
23
50
56
42
Co2(CO)8, 60 °C, 30 min;
then CyNH2 and 3, 60 °C
Co2(CO)8, CyNH2, 3, 60 °C
3, Co2(CO)8, rt, 30 min;
then CyNH2, 60 °C
4
5
18
0
71
78
a
Reactions were carried out using a substrate concentration of
0.05 M in DME with 35 mol % Co2(CO)8 and 105 mol % CyNH2
under a nitrogen atmosphere at 60 °C.
Su m m a r y a n d Con clu sion s
Methods that have been developed for the catalytic
(and stoichiometric) Pauson-Khand reactions are typi-
cally based on a combination of one or more of the
following premises: (a) in situ generation of the active
cobalt carbonyl species, (b) preservation of the active
cobalt carbonyl species, (c) preservation of the intermedi-
ate complexes, and (d) facilitation of decarbonylation,
hence increased alkene complexation rate. Furthermore,
catalysis in the Pauson-Khand reaction is best achieved
in reactions that are carried out under an atmosphere of
carbon monoxide so that regeneration of the active

3016 J . Org. Chem., Vol. 66, No. 9, 2001
Sch em e 4. Su m m a r y of Coba lt Ca ta lysis in th e P a u son -Kh a n d Rea ction
Krafft et al.
Khand reaction conditions and undergo cyclization with
the alkene and CO.36
Exp er im en ta l Section
En yn es
In conclusion, our findings have provided more practi-
cal protocols for the Pauson-Khand reaction using
catalytic amounts of cobalt carbonyl complexes. We have
provided a more general and coherent overview of the
influence of Lewis bases on the efficiency of Pauson-
Khand reactions which have recently seen substantial
interest. Finally, our findings on the use of Co4(CO)12 are
anticipated to develop into a convenient and practical
alternative to Co2(CO)8 catalysis. More detailed studies
on the interaction of these complexes with cyclohexyl-
amine in the presence of an alkyne or enyne under the
Pauson-Khand reaction conditions are underway.
1:3a 1H NMR (CDCl3, 300 MHz): δ 5.62 (dddd, J ) 17.4,
9.9, 7.4, 7.4 Hz, 1H, CHdCH2), 5.18 (dm, J ) 17.1 Hz, 1H,
CHdCHH), 5.13 (dm, J ) 9.9 Hz, 1H, CHdCHH), 4.21 (q,
J ) 7.2 Hz, 4H, 2 CH2O), 2.79-2.82 (m, 4H, 2 CH2), 2.01 (t,
J ) 2.7 Hz, 1H, CCH), 1.25 (t, J ) 7.2 Hz, 6H, 2 CH3). MS
[CI, m/z (rel intensity)]: 239.1 (M+ + 1, 100). Anal. Calcd for
C
13H18O4: C, 65.53; H, 7.61. Found: C, 65.27; H, 7.63.
3:32 1H NMR (CDCl3, 300 MHz): δ 5.63 (dddd, J ) 17.5,
10.1, 7.4, 7.4 Hz, 1H, CHdCH2), 5.16 (br d, J ) 18.1 Hz, 1H,
CHdCHH), 5.11 (br d, J ) 10.1 Hz, 1H, CHdCHH), 4.18 (q,
J ) 7.4 Hz, 4H, 2 OCH2), 2.78 (d, J ) 7.4 Hz, 2H, CH2CHdC),
2.75 (t, J ) 2.7 Hz, 2H, CH2CC-n-Pr), 2.09 (ddt, J ) 8.7, 6.7,
2.0 Hz, 2H, CCCH2CH2), 1.47 (ddq, J ) 14.1, 6.7, 6.7 Hz, 2H,
CH2CH2CH3), 1.24 (t, J ) 7.4 Hz, 6H, 2 OCH2CH3), 0.95 (t,
J ) 7.4 Hz, 3H, CH2CH3).
(32) Zhang, M.; Buchwald, S. L. J . Org. Chem. 1996, 61, 4498.
(33) Magnus, P.; Exon, C.; Albaugh-Robertson, P. Tetrahedron 1985,
41, 5861.
(34) Shambayati, S.; Crowe, W. E.; Schreiber, S. L. Tetrahedron Lett.
1990, 31, 5289.
(35) Schore, N. E.; Croudace, M. C. J . Org. Chem. 1981, 46, 5436.
(36) (a) Dickson, R. S.; Tailby, G. R. Aust. J . Chem. 1970, 23, 229.
(b) Dickson, R. S.; Fraser, P. J . Adv. Organomet. Chem. 1974, 12, 323.
(c) Cadierno, V.; Gamasa, M. P.; Gimeno, J .; Moreto, J . M.; Ricart, S.;
Roig, S.; Molins, E. Organometallics 1998, 17, 697.
4:3a 1H NMR (CDCl3, 300 MHz): δ 7.74 (d, J ) 8.2 Hz, 2H,
aromatic H), 7.30 (d, J ) 8.5 Hz, 2H, aromatic H), 5.73 (dddd,
J ) 17.2, 10.3, 6.5, 6.5 Hz, 1H, CHdCH2), 5.29 (br d, J ) 17.8
Hz, 1H, CHdCHH), 5.24 (br d, J ) 9.7 Hz, 1H, CHdCHH),
4.10 (d, J ) 2.5 Hz, 2H, CH2CCH), 3.83 (d, J ) 6.5 Hz, 2H,
CH2CHdCH2), 2.43 (s, 3H, CH3), 2.00 (t, J ) 2.5 Hz, 1H, CCH).
5: 1H NMR (CDCl3, 300 MHz): δ 5.77 (ddt, J ) 17.5, 10.1,
7.4 Hz, 1H, CHdCH2), 5.04 (br d, J ) 15.4 Hz, 1H, CHdCHH),

Catalysis in Thermal Pauson-Khand Reaction
J . Org. Chem., Vol. 66, No. 9, 2001 3017
5.00 (br d, J ) 8.7 Hz, 1H, CHdCHH), 3.56 (d, J ) 6.1 Hz,
2H, CH2OSi), 2.18-2.22 (m, 2H, CH2CHdC), 2.10-2.16 (m,
4H, CH2CCCH2), 1.66-1.75 (m, 1H, OCH2CH), 1.50 (ddt, J )
14.8, 7.4, 7.4 Hz, 2H, CH2CH2CH3), 0.97 (t, J ) 7.4 Hz, 3H,
CH2CH3), 0.89 (s, 9H, C(CH3)3), 0.04 (s, 6H, Si(CH3)2). 13C NMR
(CDCl3, 75 MHz): δ 136.7, 116.2, 81.2, 78.2, 64.3, 40.2, 34.6,
25.9, 22.5, 20.7, 19.9, 18.3, 13.5, 0.97. IR (thin film, cm-1):
2958, 2938, 2859, 1472, 1258, 1104, 913, 837, 777, 668. Anal.
Calcd for C17H32OSi: C, 72.79; H, 11.50. Found: C, 72.77; H,
11.61.
9:3b 1H NMR (CDCl3, 300 MHz): δ 4.92 (br s, 1H, CH3Cd
CHH), 4.85 (br s, 1H, CH3CdCHH), 3.74 (s, 6H, 2 OCH3),
2.83-2.85 (m, 4H, CH2CCH, CH2CdC), 2.03 (t, J ) 2.7 Hz,
1H, CCH), 1.65 (s, 3H, CH3CdC).
10:3b 1H NMR (CDCl3, 300 MHz): δ 5.70 (dt, J ) 12.1, 6.1
Hz, 1H, CdCHCH2O), 5.19 (dtm, J ) 12.7, 8.1 Hz, 1H,
CCH2CHdCHCH2O), 4.27 (d, J ) 6.0 Hz, 2H, CH2O), 3.74 (s,
6H, 2 OCH3), 2.82 (d, J ) 8.1 Hz, 2H, CH2CHdC), 2.79 (d,
J ) 2.7 Hz, 2H, CH2CCH), 2.01 (t, J ) 2.7 Hz, 1H, CCH), 0.89
(s, 9H, C(CH3)3), 0.06 (s, 6H, Si(CH3)2).
11:3b 1H NMR (CDCl3, 300 MHz): δ 5.73 (dt, J ) 13.4, 6.7
Hz, 1H, CdCHCH2O), 5.46 (dtm, J ) 13.4, 8.1 Hz, 1H,
CCH2CHdCHCH2O), 4.66 (d, J ) 6.7 Hz, 2H, CH2O), 3.75 (s,
6H, 2 OCH3), 2.89 (d, J ) 8.1 Hz, 2H, CH2CHdC), 2.80 (d,
J ) 2.7 Hz, 2H, CH2CCH), 2.06 (s, 3H, C(dO)CH3), 2.04 (t,
J ) 2.7 Hz, 1H, CCH).
12:3a 1H NMR (CDCl3, 300 MHz): δ 5.80 (dddd, J ) 16.8,
10.7, 6.7, 6.7 Hz, 1H, CHdCH2), 5.05 (ddm, J ) 17.4, 2.0 Hz,
1H, CHdCHH), 4.99 (ddm, J ) 10.1, 2.0 Hz, 1H, CHdCHH),
3.74 (s, 6H, 2 OCH3), 2.84 (d, J ) 2.4 Hz, 2H, CH2CCH), 2.14-
2.19 (m, 2H, CH2CHdC), 2.01 (t, J ) 2.7 Hz, 1H, CCH), 1.93-
1.99 (m, 2H, CH2CH2CHdC).
13: 1H NMR (CDCl3, 300 MHz): δ 5.75 (dddd, J ) 17.5,
10.1, 7.4, 7.4 Hz, 1H, CHdCH2), 5.06 (ddm, J ) 17.5, 2.0 Hz,
1H, CHdCHH), 5.02 (d, J ) 10.1 Hz, 1H, CHdCHH), 3.57
(dddd, J ) Hz, 2H, CH2OSi), 2.25 (dd, J ) 6.0, 2.7 Hz, 2H,
CH2CCH), 2.14 (dddd, J ) 6.7, 6.7, 1.3, 1.3 Hz, 2H, CH2CHd
CH2), 1.93 (t, J ) 2.7 Hz, 1H, CCH), 1.70-1.82 (m, 1H,
OCH2CH), 0.89 (s, 9H, C(CH3)3), 0.04 (s, 6H, Si(CH3)2). 13C
NMR (CDCl3, 75 MHz): δ 136.4, 116.5, 82.8, 69.2, 64.1, 39.7,
34.5, 25.9, 19.6, 18.3. IR (thin film, cm-1): 3313, 2956, 2930,
2859, 1641, 1472, 1256, 1107, 915, 838, 776, 634. Anal. Calcd
for C14H26OSi: C, 70.52; H, 10.99. Found: C, 70.30; H, 10.93.
14:33 1H NMR (CDCl3, 300 MHz): δ 5.81 (ddt, J ) 16.8, 10.7,
7.4 Hz, 1H, CHdCH2), 5.06 (br d, J ) 16.8 Hz, 1H, CHdCHH),
5.01 (br d, J ) 10.7 Hz, 1H, CHdCHH), 4.01 (d, J ) 2.0 Hz,
1H, CHOSi), 2.36 (d, J ) 2.0 Hz, 1H, CCH), 2.11 (br dd, J )
7.4, 2.7 Hz, 2H, CH2CHdC), 0.93 (s, 3H, C(CH3)CH3), 0.92 (s,
3H, C(CH3)CH3), 0.90 (s, 9 H, SiC(CH3)3), 0.15 (s, 3H, SiCH3),
0.09 (s, 3H, SiCH3.
15:33 1H NMR (CDCl3, 300 MHz): δ 5.81 (ddt, J ) 16.8, 9.4,
7.4, Hz, 1H, CHdCH2), 5.04 (br d, J ) 16.8 Hz, 1H, CHdCHH),
5.00 (br d, J ) 9.4 Hz, 1H, CHdCHH), 3.98 (app d, J ) 2.0
Hz, 1H, CHOSi), 2.08 (br dd, J ) 6.0, 6.0 Hz, 2H, CH2CHdC),
1.83 (d, J ) 2.1 Hz, 3H, CCCH3), 0.90 (s, 9 H, C(CH3)3), 0.88
(s, 6H, C(CH3)2, 0.12 (s, 3H, SiCH3), 0.07 (s, 3H, SiCH3).
18:29 1H NMR (CDCl3, 300 MHz): δ 1.26 (t, 3H, J ) 7.1 Hz,
CH2CH3), 1.57 (tt, 2H, J ) 7.1, 7.1 Hz, CH2CH2CHdC), 2.13
(obscured dtdd, 2H, J ) 7.1, 6.6, 1.6, 1.1 Hz, CH2CHdC), 2.17
(obscured tt, 2H, J ) 7.1, 2.2 Hz, CH2CCC(CH2)2S), 2.44 (tt,
2H, J ) 7.1, 2.2 Hz, CCCH2CH2S), 2.58 (q, 2H, J ) 7.1, SCH2-
CH3), 2.66 (t, 2H, J ) 7.1 Hz, CCCH2S), 4.97 (obscured ddt,
1H, J ) 9.9, 2.2, 1.1 Hz, CHdCHH), 5.03 (obscured ddt, 1H,
J ) 17, 2.2, 1.6 Hz, CHdCHH), 5.80 (ddt, 1H, J ) 17, 9.9, 6.6
Hz, CHdCH2). 13C NMR (CDCl3, 75 MHz): δ 14.9, 18.3, 20.5,
26.2, 28.3, 31.4, 33.0, 79.1, 81.3, 115.5, 138.6. IR (neat, cm-1):
1630. MS, m/e (EI): 153 (M+ - 29).
19:35 1H NMR (CDCl3, 300 MHz): δ 5.81 (dddd, J ) 16.8,
10.1, 6.1, 6.1 Hz, 1H, CHdCH2), 5.00 (dddd, J ) 17.5, 4.0, 2.0,
2.0 Hz, 1H, CHdCHH), 4.95 (dddd, J ) 10.1, 10.1, 2.0, 2.0
Hz, 1H, CHdCHH), 2.11-2.16 (m, 4H, CH2CCCH2), 2.03-2.09
(m, 2H, CH2CdC), 1.23-1.51 (m, 8H), 0.90 (t, J ) 7.5 Hz, 3H,
CH3).
38: 1H NMR (CDCl3, 500 MHz): δ 7.75 (d, J ) 8.3 Hz, 2H,
aromatic H), 7.29 (d, J ) 8.1 Hz, 2H, aromatic H), 5.75 (dddd,
J ) 16.6, 10.0, 6.4, 6.4 Hz, 1H, CHdCH2), 5.27 (dd, J ) 17.1,
1.2 Hz, 1H, CHdCHH), 5.22 (dd, J ) 10.3, 1.2 Hz, 1H, CHd
CHH), 4.06 (d, J ) 2.2 Hz, 2H, NCH2CCH), 3.81 (br d, J ) 6.6
Hz, 2H, NCH2CHdC), 2.42 (s, 3H, ArCH3), 1.89 (ddt, J ) 6.8,
6.8, 2.2 Hz, 2H, CH2CH2CH3), 1.29 (ddt, J ) 7.3, 7.3, 7.3 Hz,
2H, CH2CH2CH3), 0.82 (t, J ) 7.3 Hz, 3H, CH2CH3). 13C NMR
(CDCl3, 75 MHz): δ 143.1, 136.0, 132.0, 129.2, 127.7, 119.4,
86.0, 72.2, 48.7, 36.2, 21.6, 21.3, 20.3, 13.2. IR (thin film, cm-1):
2965, 2934, 2873, 2361, 1599, 1496, 1446, 1348, 1163, 1092,
1058, 992, 931, 901, 815, 757, 667, 580, 545. Anal. Calcd for
C
16H21NO2S: C, 65.95; H, 7.26; N, 4.81. Found: C, 66.00; H,
7.30, N, 4.86.
39: 1H NMR (CDCl3, 500 MHz): δ 5.83 (ddt, J ) 16.8, 10.3,
6.6 Hz, 1H, CHdCH2), 5.03 (dddd, J ) 17.2, 1.8, 1.8, 1.8 Hz,
1H, CHdCHH), 4.96 (ddm, J ) 10.3, 1.3 Hz, 1H, CHdCHH),
4.35 (ddt, J ) 6.6, 6.6, 1.8 Hz, 1H, CHOSi), 2.19 (obscured
ddd, J ) 7.0, 7.0, 2.0 Hz, 2H, CH2CHdC), 2.15-2.18 (m, 2H,
COCCCH2), 1.74 (dtd, J ) 16.7, 6.8, 6.8 Hz, 1H, CHHCHO),
1.71 (dtd, J ) 17.4, 6.8, 6.8 Hz, 1H, CHHCHO), 1.37-1.51 (m,
4H, CH2CH2CH3), 0.90 (s, 9H, C(CH3)3), 0.90 (t, J ) 7.0 Hz,
3H, CH3), 0.12 (s, 3H, SiCH3), 0.10 (s, 3H, SiCH3). Anal. Calcd
for C17H32OSi: C, 72.79; H, 11.50. Found: C, 72.77; H, 11.58.
45: 1H NMR (CDCl3, 500 MHz): δ 7.40-7.42 (m, 2H,
aromatic H), 7.30 (app t, J ) 2.1 Hz, 3H, aromatic H), 5.86
(ddt, J ) 16.9, 10.3, 6.6 Hz, 1H, CHdCH2), 5.07 (br dd, J )
17.1, 1.7 Hz, 1H, CdCHH), 4.99 (br dd, J ) 11.2, 1.2 Hz, 1H,
CdCHH), 4.59 (t, J ) 6.6 Hz, 1H, CHOSi), 2.27 (dtd, J ) 14.7,
7.1, 7.1 Hz, 1H, CHHCHdC), 2.25 (dtd, J ) 14.9, 6.8, 6.8 Hz,
1H, CHHCHdC), 1.87 (dtd, J ) 13.9, 7.1, 7.1 Hz, 1H,
OCHCHH), 1.84 (dtd, J ) 14.2, 7.3, 7.3 Hz, 1H, OCHCHH),
0.93 (s, 9H, C(CH3)3), 0.18 (s, 3H, SiCH3), 1.05 (s, 3H, SiCH3).).
13C NMR (CDCl3, 75 MHz): δ -4.9, -4.4, 18.2, 25.8, 29.5, 37.8,
62.8, 84.3, 90.9, 114.9, 123.1, 128.1, 128.2, 131.5, 138.0.
47: To a solution of N-tosyl-N-allylpropargylamine (492 mg,
1.97 mmol) in THF (20 mL) at -78 °C was added sec-BuLi
(2.0 mL, 2.6 mmol, 1.3 M in hexanes). The reaction was then
warmed to ambient temperature, and acetone was added (2
mL). After stirring for 30 min, the resulting mixture was
quenched with water and extracted with EtOAc. The organic
layer was dried over Na2SO4 and concentrated in vacuo.
Purification by flash chromatography (SiO2, 50% EtOAc in
hexanes) yielded 347 mg of N-tosyl-N-allyl-4-hydroxy-4-meth-
yl-2-pentynylamine (57% yield) as a colorless oil. 1H NMR
(CDCl3, 300 MHz): δ 7.74 (d, J ) 8.1 Hz, 2H, aromatic H),
7.32 (d, J ) 8.1 Hz, 2H, aromatic H), 5.74 (ddt, J ) 16.8, 10.1,
6.7 Hz, 1H, CHdCH2), 5.28 (ddm, J ) 17.4, 1.3 Hz, 1H, CHd
CHH), 5.24 (ddm, J ) 10.4, 1.4 Hz, 1H, CHdCHH), 4.09 (s,
2H, CH2CCCO), 3.82 (d, J ) 6.0 Hz, 2H, CH2CHdCH2), 2.42
(s, 3H, CH3Ar), 1.6 (s, 1H, OH), 1.26 (s, 6H, C(CH3)2O). 13C
NMR (CDCl3, 75 MHz): δ 143.48, 135.98, 131.76, 129.43,
127.70, 119.76, 90.42, 74.28, 64.53, 48.92, 35.87, 30.86, 21.34.
IR (neat, cm-1): 3515, 2982, 2930, 1598, 1446, 1348, 1235,
1162, 1093, 949, 890, 855, 816, 760, 665. Anal. Calcd for
16:33 1H NMR (CDCl3, 300 MHz): δ 5.82 (ddt, J ) 16.8, 10.7,
7.4 Hz, 1H, CHdCH2), 5.05 (br d, J ) 16.8 Hz, 1H, CHdCHH),
5.00 (br dd, J ) 10.7, 2.0 Hz, 1H, CHdCHH), 4.00 (s, 1H,
CHOSi), 2.10 (dd, J ) 7.4, 3.4 Hz, 2H, CH2CHdC), 0.91 (s,
6H, C(CH3)2), 0.90 (s, 9H, C(CH3)3), 0.15 (s, 9H, Si(CH3)3), 0.14
(s, 3H, OSiCH3), 0.08 (s, 3H, OSiCH3).
17:34 1H NMR (CDCl3, 300 MHz): δ 5.82 (dddd, J ) 18.1,
10.7, 7.4, 7.4 Hz, 1H, CHdCH2), 5.04 (br dm, J ) 18.1 Hz,
1H, CHdCHH), 4.99 (br dm, J ) 10.1 Hz, 1H, CHdCHH), 3.54
(dd, J ) 4.7, 4.7 Hz, 1H, CHOSi), 2.51 (ddd, J ) 17.5, 4.7, 2.7
Hz, 1H, CHHCCH), 2.20 (ddd, J ) 17.5, 5.4, 2.7 Hz, 1H,
CHHCCH), 2.08 (ddm, J ) 14.1, 7.4 Hz, 1H, CHHCHdC), 2.02
(obscured ddm, J ) 14.7, 6.9 Hz, 1H, CHHCHdC), 1.98
(obscured t, J ) 2.7 Hz, 1H, CH2CCH), 0.90 (s, 9H, SiC(CH3)3),
0.87 (s, 3H, C(CH3)CH3, 0.86 (s, 3H, CCH3(CH3), 0.15 (s, 3H,
SiCH3CH3), 0.08 (s, 3H, SiCH3CH3).
C
16H21O3NS: C, 62.51; H, 6.89. Found: C, 62.42; H, 6.81.

3018 J . Org. Chem., Vol. 66, No. 9, 2001
Krafft et al.
En yn e-Co2(CO)6 Com p lexes
P a u son -Kh a n d R ea ct ion s Usin g Su bst oich iom et r ic
Am ou n ts of Co2(CO)8 u n d er a Nitr ogen Atm osp h er e. In
a round-bottom vessel equipped with a balloon of ultrahigh
purity (UHP) nitrogen, diethylpropargyl allyl malonate 1 (51
mg, 0.21 mmol), Co2(CO)8 (26 mg, 0.076 mmol, 38 mol %), and
DME (2.3 mL) were added. After stirring for 30 min at ambient
temperature, cyclohexylamine (25 µL, 0.22 mmol, 105 mol %)
in DME (2 mL) was added, and the reaction was heated at 60
°C for 3 h. Upon completion of the reaction, the mixture was
cooled to room temperature, diluted with 3 mL of 10% EtOAc
in hexanes, and plugged through a pad of silica gel. Subse-
quent removal of the solvent and purification by flash chro-
matography (SiO2, 20% EtOAc in hexanes) afforded 45 mg of
bicyclopentenone 2 (80% yield) as a colorless oil.
Dod eca ca r bon yltetr a coba lt Ca ta lysis in th e Th er m a l
P a u son -Kh a n d Rea ction . In a vessel equipped with a three-
way stopper and a balloon of CO, a mixture of enyne 3 (31
mg, 0.11 mmol) and Co4(CO)12 (3 mg, 0.05 mmol, 5 mol %) was
pumped briefly and purged three times with CO. DME (1.2
mL) and CyNH2 (3.6 µL, 0.031 mmol, 30 mol %) in DME (1
mL) were added successively, and the resulting deep purple
solution was heated at 70 °C for 13 h. Upon completion of the
reaction, the brown mixture was cooled to room temperature,
diluted with 3 mL of 10% EtOAc in hexanes, and plugged
through a pad of silica gel. Subsequent removal of the solvent
and purification by flash chromatography (SiO2, 20% EtOAc
in hexanes) afforded 32 mg of bicyclopentenone 6 (94% yield)
as a colorless oil. For the reactions using Co4(CO)12 only, the
reagents were dissolved in the appropriate solvent, and the
mixture was heated to 70 °C.
En yn e-Co2(CO)6 Com p lex 32. To a solution of N-tosyl-
N-allyl-4-hydroxy-4-methyl-2-pentynylamine (159 mg, 0.517
mmol) in a 1:1 mixture of petroleum ether:CH2Cl2 (5 mL) was
added solid Co2(CO)8 (220 mg, 0.643 mmol) at room temper-
ature. After stirring for 30 min, the reaction mixture was
directly subjected to column chromatography (SiO2, 50%
petroleum ether in Et2O). Concentration of the eluent at room
temperature in vacuo gave 260 mg of 25 (90% yield) as a red-
brown solid. 1H NMR and IR spectra of this complex could not
be obtained. Anal. Calcd for C22H21O9NSCo2: C, 44.53; H, 3.57.
Found: C, 44.44; H, 3.62.
En yn e-Co2(CO)6 Com p lex 33. To a solution of enyne 1
(101 mg, 0.424 mmol) in petroleum ether (4 mL) was added
solid Co2(CO)8 (160 mg, 0.468 mmol), and the mixture was
stirred under a nitrogen atmosphere at room temperature for
1 h (or until complex formation was complete by TLC).
Filtration through a short pad of Celite (eluent petroleum
ether) followed by concentration under reduced pressure at
room temperature gave a quantitative yield of enyne-Co2(CO)6
1
complex 33. H NMR (CDCl3, 300 MHz): δ 5.98 (s, 1H, CH2-
CCH), 5.68 (dddd, J ) 17.5, 10.1, 7.4, 7.4 Hz, 1H, CHdCH2),
5.18 (dm, J ) 10.1 Hz, 1H, CHdCHH), 5.13 (dm, J ) 17.0 Hz,
1H, CHdCHH), 4.27 (dq, J ) 14.8, 7.4 Hz, 2H, 2 CH2O), 4.17
(dq, J ) 14.1, 7.4 Hz, 2H, 2 CH2O), 3.62 (2, 2H, CH2CCH),
2.76 (d, J ) 7.4 Hz, 2H, 2 CH2CHdC), 1.26 (t, J ) 7.4 Hz, 6H,
2 CH3). Enyne-Co2(CO)6 complexes 35 and 37 were prepared
in the same manner as enyne-Co2(CO)6 complex 33.
Rep r esen ta tive Exp er im en ta l P r oced u r es for Cyclo-
a d d ition s. A typical procedure from each section is described.
Progress of the reactions was monitored by TLC by taking a
sample of the reaction mixture using a long capillary tube
inserted through the septum with the aid of a needle. For
reactions using volatile enyne substrates, e.g., 18, 19, and
phenylacetylene, the system was not pumped, but rather only
purged with the appropriate reaction atmosphere. For reac-
tions yielding volatile products, e.g., 29, 30, diethyl ether was
used as the eluent for filtration and the organic layer was
concentrated in vacuo at room temperature. Additives were
typically added as premixed solutions in DME, except for
solids, e.g., 1,10-phenanthroline.
A similar general procedure was followed for the intermo-
lecular variant. In a flask equipped with a three-way stopper
and a balloon of CO, a mixture of phenylacetylene (34 mg, 0.33
mmol), norbornene (157 mg, 1.7 mmol), and Co4(CO)12 (19 mg,
0.03 mmol, 10 mol %) was purged three times with a balloon
of CO. DME (5.7 mL) and a solution of CyNH2 (22.8 µL, 0.199
mmol, 60 mol %) in DME (1 mL) were added successively, and
the resulting deep purple solution was heated at 70 °C for 13.5
h. The mixture was worked up in the same manner as
described above and 72 mg of cyclopentenone 44 (97%) was
obtained as a white solid.
Mod ifica tion a n d Lim ita tion s in th e Livin gh ou se
Ca ta lytic Rea ction . In a flask equipped with a three-way
stopper and a balloon of CO, a mixture of diethyl(2-hexynyl)
allylmalonate 3 (121 mg, 0.432 mmol) and Co2(CO)8 (15 mg,
0.044 mmol, 10 mol %) was pumped briefly and purged three
times with CO. DME (1.6 mL) was added, and the resulting
solution was stirred at ambient temperature for 30 min.
Cyclohexylamine (10 µL, 0.087 mmol, 20 mol %) in DME (0.6
mL) was then added, and the reaction was heated at 70 °C for
11.5 h. Upon completion of the reaction, the mixture was cooled
to room temperature, diluted with 3 mL of 10% EtOAc in
hexanes and plugged through a pad of silica gel. Subsequent
removal of the solvent and purification by flash chromatog-
raphy (SiO2, 10% EtOAc in hexanes) afforded 120 mg of bicyclic
enone 6 (90% yield) as a colorless oil. For the reaction without
the amine, the mixture was also stirred for 30 min at room
temperature prior to heating at 70 °C and was worked up in
the same manner upon completion.
Dicoba lth exa ca r bon yl-Com p lexed En yn es a s Ca ta lyst
P r ecu r sor s. A 10-mL flask containing a mixture of enyne 1
(51 mg, 0.21 mmol) and catalyst 32 (12 mg, 0.020 mmol, 10
mol %) was equipped with a three-way stopper, a condenser,
and a balloon of CO and was pumped briefly and purged three
times with CO. DME (1 mL) was added, and the resulting
solution was heated at 70 °C and stirred for 2 h. Upon
completion of the reaction, the mixture was cooled to room
temperature, quenched with water, and extracted with EtOAc.
The organic layer was dried over Na2SO4 and concentrated in
vacuo. Purification by flash chromatography (SiO2, 33% EtOAc
in hexanes) afforded 44 mg of bicyclopentenone 2 (78% yield)
as a colorless oil. If appropriate, cyclohexylamine was added
prior to heating. Alternatively, the reaction could be worked
up by dilution with 10% EtOAc in hexanes and plugged
through a pad of silica gel using hexane/EtOAc as the eluent.
P a u son -Kh a n d Rea ction Cycloa d d u cts
2:17,3a,e,12b 1H NMR (CDCl3, 500 MHz): δ 5.92 (s, 1H, Cd
CH), 4.25 (q, J ) 7.3 Hz, 2H, OCH2), 4.21 (q, J ) 7.3 Hz, 2H,
OCH2), 3.35 (AB, J AB ) 19.1 Hz, 1H, CHHCdC), 3.25 (AB,
J AB ) 18.8 Hz, 1H, CHHCdC), 3.10 (br m, 1H, CH2CHCH2),
2.80 (dd, J ) 12.7, 7.6 Hz, 1H, CHHCdO), 2.63 (dd, J ) 17.8,
6.4 Hz, 1H, (EtO2C)2CCHHCH), 2.13 (dd, J ) 17.8, 3.2 Hz,
1H, (EtO2C)2CCHHCH), 1.74 (dd, J ) 12.7, 12.7 Hz, 1H,
CHHCdO), 1.28 (t, J ) 7.1 Hz, 3H, OCH2CH3), 1.26 (t, J )
7.3 Hz, 3H, OCH2CH3). MS [CI, m/z (rel intensity)]: 267.1
(M+ + 1, 100).
6:12a,32 1H NMR (CDCl3, 300 MHz): δ 4.25 (q, J ) 7.4 Hz,
2H, OCH2), 4.21 (q, J ) 7.4 Hz, 2H, OCH2), 3.22 (br s, 2H,
CH2CdC), 2.96 (br m, 1H, CH2CHCH2), 2.79 (dd, J ) 12.8,
7.4 Hz, 1H, CHHCdO), 2.64 (dd, J ) 17.5, 6.0 Hz, 1H,
(EtO2C)2CCHHCH), 2.22 (dt, J ) 14.8, 7.4 Hz, 1H, Cd
CCHHCH2), 2.07 (obscured dt, J ) 14.8, 7.4 Hz, 1H, Cd
CCHHCH2), 2.08 (obscured dd, J ) 17.5, 3.4 Hz, 1H,
(EtO)2CCHHCH), 1.64 (dd, J ) 12.8, 12.8 Hz, 1H, CHHCd
O), 1.48 (dqt, J ) 14.7, 7.4, 7.4, 1H, CH2CHHCH3), 1.47 (dqt,
J ) 14.7, 7.4, 7.4, 1H, CH2CHHCH3), 1.28 (t, J ) 7.4 Hz, 3H,
2 OCH2CH3), 1.26 (t, J ) 7.4 Hz, 3H, 2 OCH2CH3), 0.89 (t,
J ) 7.4 Hz, 3H, CH2CH2CH3). Anal. Calcd for C17H24O5: C,
66.21; H, 7.85. Found: C, 65.39; H, 7.87.
7:3a,e,5,8 1H NMR (CDCl3, 500 MHz): δ 7.73 (d, J ) 8.1 Hz,
2H, aromatic H), 7.35 (d, J ) 8.3 Hz, 2H, aromatic H), 5.99 (s,
1H, CdCH), 4.34 (AB, J AB ) 16.4 Hz, 1H, NCHHCdC), 4.04
(obscured AB, J AB ) 16.4 Hz, 1H, NCHHCdC), 4.03 (obscured
dd, J ) 8.8, 8.8 Hz, 1H, NCHHCH), 3.15 (br m, 1H,
CH2CHCH2), 2.63 (obscured dd, J ) 11.0, 9.3 Hz, 1H, NCH-
HCH), 2.59 (obscured dd, J ) 18.1, 6.6 Hz, 1H, CHHCdO),
2.44 (s, 3H, ArCH3), 2.06 (dd, J ) 17.8, 3.7 Hz, 1H, CHHCd
O).

Catalysis in Thermal Pauson-Khand Reaction
J . Org. Chem., Vol. 66, No. 9, 2001 3019
8 (m a jor isom er ): 1H NMR (CDCl3, 500 MHz): δ 3.62 (d,
J ) 6.6 Hz, 2H, CH2OSi), 2.86-2.92 (br m, 1H, CH2CHCH2),
2.68 (ABd, J AB ) 18.0, 8.4 Hz, 1H, CHCHHCdC), 2.62 (dd,
J ) 18.0, 6.4 Hz, 1H, CHHCdO), 2.52 (m, 1H, CHCH2OSi),
2.29 (ABd, J AB) 18.0, J ) 4.2 Hz, 1H, CHCHHCdC), 2.22 (dt,
J ) 14.3, 7.9 Hz, 1H, CdCCHHCH2), 1.96-2.13 (m, 2H, Cd
CCHHCH2 and CHCHHCH), 1.98 (dd, J ) 18.0, 3.1 Hz, 1H,
CHHCdO), 1.47 (ABtq, J ) 15.0, 7.5 Hz, 1H, CHHCH3), 1.47
(ABtq, J ) 15.0, 7.5 Hz, 1H, CHHCH3), 1.24 (ABd, J AB ) 9.0,
J ) 12.4, 12.4 Hz, 1H, CHCHHCH), 0.91 (s, 9H, C(CH3)3), 0.88
(t, J ) 4.5 Hz, 3H, CH2CH3), 0.07 (s, 6H, Si(CH3)2). Anal. Calcd
for C18H32O2Si‚0.1H2O: C, 69.66; H, 10.39. Found: C, 69.26;
H, 10.52.
IR (neat, cm-1): Min or isom er ; 2958, 2929, 2858, 1710,
1666, 1471, 1360, 1253, 1103, 1005, 836, 779. Ma jor isom er ;
2958, 2931, 2858, 1711, 1664, 1360, 1253, 1105, 1005, 838, 777.
MS [EI, m/z (rel intensity)]: 175.0 (52), 251.0 (100), 308.0 (M+).
20:5 1H NMR (CDCl3, 300 MHz): δ 5.84 (br d, J ) 1.2 Hz,
1H, CdCH), 3.81 (s, 3H, OCH3), 3.73 (s, 3H, OCH3), 3.51 (ABd,
J ) 18.1, 2.0 Hz, 1H, CHHCdC), 3.22 (ABd, J ) 18.0 Hz, 1H,
CHHCdC), 2.60 (AB, J AB ) 13.2 Hz, 1H, (MeO2C)2CHHCCH3),
2.39 (s, 2H, CH2CdO), 2.23 (AB, J AB ) 13.3 Hz, 1H, (MeO2C)2-
CHHCH3, 1.15 (s, 3H, CCH3).
Me2CHH), 1.99 (dd, J ) 18.1, 2.7 Hz, 1H, CHHCdO), 1.75 (d,
J ) 2.0 Hz, 3H, CdCCH3), 1.12 (s, 3H, C(CH3)CH3), 1.04 (dd,
J ) 13.4, 7.4 Hz, 1H, Me2CHH), 0.88 (s, 9H, SiC(CH3)3), 0.80
(s, 3H, C(CH3)CH3), 0.10 (s, 3H, SiCH3CH3), 0.01 (s, 3H,
SiCH3CH3).
28 (m a jor isom er ): 1H NMR (C6D6, 500 MHz): δ 5.67 (s,
1H, CdCH), 3.04 (dd, J ) 11.0, 4.5 Hz, 1H, CHOSi), 2.46 (dd,
J ) 13.4, 5.1, 1H, CHHCdCH), 2.21 (dd, J ) 18.3, 6.6 Hz,
1H, CHHCdO), 2.10 (dddm, J ) 13.0, 6.5, 6.5, 1H, CH2CHCH2),
2.05 (t, J ) 12.4, 1H, CHHCdCH), 1.62 (dd, J ) 18.3, 2.3, 1H,
CHHCdO), 1.22 (dd, J ) 13.2, 5.7, 1H, (CH3)2CCHHCH), 0.95
(s, 9H, SitBu), 0.79 (s, 3H, CCH3CH3), 0.77 (s, 3H, CCH3CH3),
0.41 (t, J ) 13.0, 1H, (CH3)2CCHHCH), -0.01 (s, 3H, SiCH3-
CH3), -0.02 (s, 3H, SiCH3CH3). (CDCl3, 75 MHz): -5.0, -4.1,
17.8, 17.9, 25.7, 28.8, 36.5, 36.9, 37.5, 41.9, 45.2, 77.3, 128.0,
182.0, 209.1. Anal. Calcd for C17H30O2Si: C, 69.33; H, 10.27.
Found: C, 69.26; H, 10.28. CH2CHCH2
29:29 1H NMR (CDCl3, 300 MHz): δ 1.07 (dddd, 1H, J )
11.5, 11.5, 11.5, 8.3, 6-H), 1.23 (t, 3H, J ) 7.7, 12-H), 1.90-
2.20 (m, 5 H), 2.37 (ABt, 1H, J AB ) 14.3, J ) 7.1, 9-H), 2.45-
2.70 (m, 7 H), 2.77 (m, 1H, 7-H). 13C NMR (CDCl3, 75 MHz):
δ 14.9, 24.5, 25.5, 25.8, 26.0, 30.1, 31.4, 41.9, 44.8, 134.9, 185.9,
210.9.
21:3b 1H NMR (C6D6, 500 MHz): δ 5.70 (br s, 1H, CdCH),
3.78 (ABd, J AB ) 10.2, J ) 6.4 Hz, 1H, CHHOSi), 3.66 (ABd,
J AB ) 10.2, J ) 3.0 Hz, 1H, CHHOSi), 3.30 (s, 3H, OCH3),
3.28 (s, 3H, OCH3), 3.12 (AB, J AB ) 19.1 Hz, 1H, (MeO2C)2-
CCHHCdC), 3.06 (AB, J AB ) 19.1 Hz, 1H, (MeO2C)2CCHHCd
C), 2.91 (dddm, J ) 13.2, 6.6, 6.6 Hz, 1H, CH2CHCHCdO),
2.69 (dd, J ) 12.6, 7.7 Hz, 1H, (MeO2C)2CCHHCH), 2.41 (dd,
J ) 12.8, 12.8 Hz, 1H, (MeO2C)2CCHHCH), 2.35 (ddd, J )
6.6, 6.6, 3.0 Hz, 1H, CHCHCH2O), 0.87 (s, 9H, C(CH3)3, 0.00
(s, 3H, SiCH3CH3), -0.03 (s, 3H, Si(CH3)CH3).
30:29 1H NMR (CDCl3, 300 MHz): δ 2.82-2.87 (m, 1H),
2.49-2.57 (m, 2H), 2.09-2.17 (m, 4H), 1.94-2.04 (m, 2H),
1.81-1.89 (m, 2H), 1.48 (m, 1H), 1.21-1.39 (m, 4H), 1.03 (ddd,
J ) 15.9, 13.2, 3.9 Hz, 1H), 0.88 (t, J ) 7.5 Hz, 3H).
34:221H NMR (CDCl3, 500 MHz): δ 7.74 (d, J ) 8.3 Hz, 2H,
aromatic H), 7.35 (d, J ) 8.1 Hz, 2H, aromatic H), 4.36 (AB,
J AB ) 17.3 Hz, 1H, NCHHCdC), 4.23 (AB, J AB ) 17.1 Hz, 1H,
NCHHCdC), 3.99 (dd, J ) 8.5, 8.5 Hz, 1H, NCHHCH), 2.99
(br m, 1H, CH2CHCH2), 2.60 (obscured dd, J ) 18.8, 6.4 Hz,
1H, CHHCdO), 2.56 (obscured dd, J ) 11.2, 9.5 Hz, 1H,
NCHHCH), 2.44 (s, 3H, ArCH3), 2.07 (dd, J ) 18.1, 3.9 Hz,
1H, CHHCdO), 1.38 (s, 3H, CCH3CH3O), 1.35 (s, 3H,
CCH3CH3O).
40:3a,3e,5,8 1H NMR (CDCl3, 500 MHz): δ 7.73 (d, J ) 8.3
Hz, 2H, aromatic H), 7.34 (d, J ) 8.5 Hz, 2H, aromatic H),
4.24 (AB, J AB ) 16.0 Hz, 1H, NCHHCdC), 4.02 (obscured AB,
J AB ) 16.2 Hz, 1H, NCHHCdC), 3.99 (obscured dd, J ) 8.9,
8.9 Hz, 1H, NCHHCH), 3.02 (br m, 1H, CH2CHCH2), 2.59
(obscured dd, J ) 17.9, 6.4 Hz, 1H, CHHCdO), 2.56 (obscured
dd, J ) 11.1, 9.4 Hz, 1H, NCHHCH), 2.44 (s, 3H, ArCH3), 2.18
(dt, J ) 14.5, 7.2 Hz, 1H, CdCCHHCH2), 2.03 (obscured dt,
J ) 14.5, 7.2 Hz, 1H, CdCCHHCH2), 2.02 (obscured dd, J )
17.9, 3.4, 1H, CHHCdO), 1.41 (dqt, J ) 13.8, 7.2, 7.2 Hz, 1H,
CH2CHHCH3), 1.40 (dqt, J ) 13.8, 7.2, 7.2 Hz, 1H, CH2-
CHHCH3, 0.81 (t, J ) 7.4 Hz, 3H, CH2CH2CH3).
22:3b 1H NMR (CDCl3, 300 MHz): δ 5.96 (s, 1H, CdCH),
4.28 (dd, J ) 11.4, 4.7 Hz, 1H, CHHOAc), 4.06 (dd, J ) 11.4,
8.7 Hz, 1H, CHHOAc), 3.81 (s, 3H, OCH3), 3.77 (s, 3H, OCH3),
3.41 (br AB, J ) 19.5 Hz, 1H, CHHCHdC), 3.27 (obscured
broad AB, J ) 19.5 Hz, 1H, CHCHdC), 3.24 (obscured m, 1H,
CH2CHCH), 2.92 (ddd, J ) 4.7, 6.7, 8.7 Hz, 1H, CHCH2O),
2.66 (dd, J ) 12.8, 7.4 Hz, 1H, (MeO2C)2CHHCH), 2.04 (s, 3H,
COCH3), 1.92 (dd, J ) 12.8, 12.8 Hz, 1H, (MeO2C)2CHHCH).
23:3a 1H NMR (CDCl3, 400 MHz): δ 5.97 (s, 1H, CdCH),
3.76 (s, 3H, OCH3), 3.72 (s, 3H, OCH3), 3.49 (dd, J ) 14.0, 2.3
Hz, 1H, CHHCdC), 2.68 (obscured m, 1H, CH2CHCH2), 2.67
(br d, J ) 14.2 Hz, 1H, CHHCdC), 2.57 (dd, J ) 18.7, 6.6 Hz,
1H, CHHCdO), 2.52 (ddd, J ) 14.0, 6.0, 3.2 Hz, (MeO2C)2-
CCHHCH2), 2.17 (dddd, J ) 13.6, 6.0, 3.8, 3.4 Hz, 1H,
(MeO2C)2CCH2CHH), 1.98 (obscured dd, J ) 18.5, 2.1 Hz, 1H,
CHHdO), 1.94 (ddd, J ) 13.8, 13.8, 3.8 Hz, 1H, (MeO2C)2-
CHHCH2), 1.28 (dddd, J ) 13.6, 13.6, 3.6, 3.2 Hz, 1H,
(MeO2C)2CCH2HH).
41 (m a jor isom er ): 1H NMR (CDCl3, 500 MHz): δ 4.80
(dd, J ) 3.6, 3.6 Hz, 1H, CHOSi), 3.06 (br m, 1H, CH2CHCH2),
2.66 (dd, J ) 18.1, 6.3 Hz, 1H, CHHCdO), 2.30 (dddd, J )
13.6, 8.8, 6.8, 2.6 Hz, 1H, CHOCHH), 2.15-2.23 (m, 4H), 2.00
(dd, J ) 18.1, 2.7 Hz, 1H, CHHCdO), 1.86 (dddd, J ) 13.6,
10.1, 7.9, 4.2 Hz, 1H, CHOCHH), 1.37-1.51 (m, 3H), 1.26-36
(m, 3H), 0.99 (dddd, J ) 19.6, 10.8, 8.8, 4.4 Hz, 1H, CH2-
CHHCH), 0.90 (s, 9H, C(CH3)3), 0.13 (s, 3H, SiCH3CH3), 0.11
(s, 3H, SiCH3CH3). MS [EI, m/z (rel intensity)]: 75.0 (56), 271.1
(100). Anal. Calcd for C20H28O2Si‚0.5H2O: C, 71.17; H, 8.36.
Found: C, 71.49; H, 8.37.
44:5 1H NMR (CDCl3, 500 MHz): δ 7.70 (m, 2H, aromatic
H), 7.64 (d, J ) 3.0 Hz, 1H, CdCH), 7.36-7.39 (m, 2H,
aromatic H), 7.31-7.34 (m, 1H, aromatic H), 2.71 (dd, J ) 3.2,
4.9 Hz, 1H), 2.50 (br d, J ) 3.8 Hz, 1H), 2.37 (d, J ) 5.3 Hz,
1H), 2.28 (br d, J ) 4.3 Hz, 1H), 1.72 (dddd, J ) 13.6, 11.9,
4.3, 4.3 Hz, 1H), 1.62 (dddd, J ) 13.6, 11.9, 4.3, 4.3 Hz, 1H),
1.38 (dddd, J ) 2.3, 3.8, 9.3, 9.3 Hz, 1H), 1.33 (dddd, J ) 2.3,
3.8, 9.3, 9.3 Hz, 1H), 1.13 (apparent dt, J ) 10.6, 1.7 Hz, 1H),
1.00 (apparent dt, J ) 10.6, 1.3 Hz, 1H).
24. Inseparable (1:1) mixture of isomers. Anal. Calcd for
C
15H25O2Si: C, 67.62; H, 9.83. Found: C, 67.6; H, 9.96.
25 (m a jor isom er ): 1H NMR (CDCl3, 500 MHz): δ 5.93
(d, J ) 2.1 Hz, 1H, CdCH), 4.11 (s, 1H, CHOSi), 3.30-3.41
(m, 1H, CH2CHCH2), 2.69 (dd, J ) 18.1, 6.7 Hz, 1H, CHHCd
O), 2.04 (dd, J ) 18.1, 3.4 Hz, 1H, CHHCdO), 2.01 (dd, J )
12.1, 12.1 Hz, 1H, Me2CCHH), 1.11 (obscured s, 3H, CCH3-
CH3), 1.08 (obscured dd, J ) 12.8, 8.1 Hz, Me2CCHH), 0.90 (s,
3H, CCH3CH3), 0.89 (s, 9H, C(CH3)3), 0.10 (s, 3H, SiCH3CH3),
0.04 (s, 3H, SiCH3CH3).). 13C NMR (CDCl3, 75 MHz): -5.1,
-4.9, 18.0, 24.4, 25.6, 29.0, 37.0, 43.7, 43.8. Anal. Calcd for
C
16H28O2Si: C, 68.52; H, 10.06. Found: C, 68.34; H, 10.11.
25 (m in or isom er ): 1H NMR (CDCl3, 500 MHz): δ 5.98 (t,
J ) 2.0 Hz, 1H, CdCH), 4.47 (d, J ) 1.5 Hz, 1H, CHOSi),
2.94-3.00 (m, 1H, CH2CHCH2), 2.67 (dd, J ) 17.8, 6.6 Hz,
1H, CHHCdO), 2.06 (dd, J ) 17.8, 3.2 Hz, 1H, CHHCdO),
2.00 (dd, J ) 13.2, 10.0 Hz, 1H, Me2CCHH), 1.31 (dd, J ) 13.2,
8.3 Hz, 1H, Me2CHH), 1.18 (s, 3H, CCH3CH3, 0.93 (s, 9H,
C(CH3)3, 0.85 (s, 3H, CCH3CH3), 0.10 (s, 3H, SiCH3CH3). 0.09
(s, 3H, SiCH3CH3).
26 (cis isom er ):12b,45 1H NMR (CDCl3, 300 MHz): δ 4.09 (s,
1H, CHOSi), 3.22 (br m, 1H, CH2CHCH2), 2.72 (dd, J ) 18.1,
6.0 Hz, 1H, CHHCdO), 2.01 (dd, J ) 12.8, 10.8 Hz, 1H,
46 (m a jor isom er ): 1H NMR (CDCl3, 500 MHz): δ 7.63
(m, 2H, aromatic H), 7.32-7.40 (m, 3H, aromatic H), 4.82 (br
dd, J ) 5.5, 5.5 Hz, 1H, CHOSi), 3.23 (m, 1H, CH2CHCH2),
2.85 (dd, J ) 18.1, 6.4 Hz, 1H, CHHCdO), 2.37 (dddd, J )
13.7, 8.6, 6.6, 2.0 Hz, 1H, CHOCHH), 2.28 (m, 1H, CH2CH-
HCH), 2.23 (dd, J ) 18.1, 2.8 Hz, 1H, CHHCdO), 1.95 (dddd,

3020 J . Org. Chem., Vol. 66, No. 9, 2001
Krafft et al.
J ) 13.6, 10.6, 7.7, 4.3 Hz, CHOCHH), 1.07 (dddd, J ) 19.6,
12.3, 10.8, 8.8 Hz, 1H, CH2CHHCH), 0.94 (s, 9H, C(CH3)3, 0.12
(s, 3H, SiCH3CH3), 0.10 (s, 3H, SiCH3CH3). MS [EI, m/z (rel
intensity)]: 75.0 (56), 271.1 (100). Anal. Calcd for C20H28O2-
Si‚0.5H2O: C, 71.17; H, 8.36. Found: C, 71.49; H, 8.37.
Ack n ow led gm en t. Support for this work was pro-
vided by the National Science Foundation and donors
to the Krafft Research Fund.
J O0057708