(Alkylthio)alkynes as addends in the Co(0) catalyzed intramolecular pauson-khand reaction. Substituent driven enhancements of annulation efficiency and stereoselectivity

Article abstract of DOI:10.1055/s-2000-6301

Compared to terminal alkynes, (methylthio)alkynes are generally superior substrates for the thermally promoted, Co₂(CO)₈ catalyzed Pauson-Khand reaction of enynes and allenynes, providing enones in higher yields and with enhanced diastereoselectivity. Improvements in yield dependent upon the use of 2,2,2-trifluoroethanol as co-solvent and an apparent preference for endo selectivity with (ethoxy)alkynes are also disclosed.

Full text of DOI:10.1055/s-2000-6301

PAPER
1009
(Alkylthio)alkynes as Addends in the Co(0) Catalyzed Intramolecular
Pauson-Khand Reaction. Substituent Driven Enhancements of Annulation
Efficiency and Stereoselectivity
Brian L. Pagenkopf,2 David B. Belanger,3 Donogh J. R. O’Mahony,4 Tom Livinghouse1,*
Department of Chemistry and Biochemistry, Montana State University, Bozeman, MT 59717, USA
E-mail: Livinghouse@chemistry.montana.edu
Received 8 February 2000; revised 22 February 2000
been previously examined as substrates in Co2(CO)8 pro-
Abstract: Compared to terminal alkynes, (methylthio)alkynes are
moted [2+2+1] cycloadditions.13,14 In this contribution we
show that substrate modification of terminal alkynes
via sulfenylation can lead to noteworthy enhancements
generally superior substrates for the thermally promoted, Co2(CO)8
catalyzed Pauson-Khand reaction of enynes and allenynes, provid-
ing enones in higher yields and with enhanced diastereoselectivity.
Improvements in yield dependent upon the use of 2,2,2-trifluoro- of both reaction efficiency and stereoselectivity of the
ethanol as co-solvent and an apparent preference for endo selectiv-
ity with (ethoxy)alkynes are also disclosed.
intramolecular Co(0) catalyzed PKR.
We began our investigation with enyne 1a, a substrate that
Key words: annulations, carbonylations, catalysis, diastereoselec-
we had previously found to undergo the thermal Co(0)-
tivity, sulfides
catalyzed PKR [5 mol% Co2(CO)8, CO (1 atmosphere),
1,2-DME, 60 °C] with only poor efficiency, affording the
expected enones 1b (<50%) along with the diene 1c15
The Pauson-Khand Reaction (PKR) has come to be re-
garded as one of the most convergent and useful methods
for effecting cyclopentenone annulations.5 In 1996, we
disclosed that high-intensity visible light can promote
Co(0) catalyzed Pauson-Khand reactions at 50-55 °C
and 1 atmosphere of CO pressure.6 Our observations that
temperatures of at least 50 °C are necessary for the photo-
promoted PKR suggested that the thermal dependency of
the cobalt catalyzed process had been poorly appreciated.
Upon close examination it was ascertained that a particu-
larly narrow thermal window exists for the realization of
the corresponding non-photo assisted process, but that
these annulations can be readily executed using 5-10
mol% of high purity Co2(CO)8 at 60 °C under one atmo-
sphere of CO.7a Although similar catalytic transforma-
tions have been recently achieved using titanium,8
ruthenium9 and rhodium10 derived catalysts, the Co(0)
catalyzed process would appear preferable in terms of its
generality, experimental simplicity and independence
from chemically labile catalysts.7b
(Scheme 1). Interestingly, an analogous cyclization of 1a
in the mixed solvent system CF3CH2OH (TFE)/1,2-DME
(2:1) furnished the desired enones 1bb and 1ba (1bb/
1ba = 1.6) in 80% yield to the exclusion of 1c.16 By way
of contrast, the carbonylative cyclization of the (methyl-
thio)enyne 2a17 in 1,2-DME alone (vide supra) gave
enones 2bb and 2ba with improved diastereoselectivity
(2bb/2ba = 3.9) in 99% isolated yield (Scheme 2).
1 ATM CO
5 mol % Co2(CO)8
Me
Me
1,2-DME
60 °C, (< 50%)
tBuMe2SiO
1a
Me
Me
+
O
Me
Me
tBuMe2SiO
tBuMe2SiO
1b
1c
Scheme 1
Close examination of the results obtained from the assort-
ed metal mediated intramolecular PKR variants reveals
considerable disparity in substrate tolerance and cycliza-
tion efficiency. In addition, it has previously been recog-
nized that electronic and conformational modification of
the enyne substrate could lead to notable alterations in the
annulative efficiency and stereoselectivity of the classical,
stoichiometric PKR.5b For example, in pioneering investi-
gations on the PKR, Magnus showed that annulation of
(trimethylsilyl)alkynes displayed improved diastereose-
lectivity over their terminal alkyne counterparts.11 Addi-
1 ATM CO
5 mol % Co2(CO)8
e
TFE : 1,2-DME (2 : 1) (for 1a)
1,2-DME (for 2a)
60 °C
e
X
2SiO
1a, X = H
N
2a, X = SMe
(63%)
Me
Me
+
O
O
Me
Me
X
tBuMe2SiO
X
tBuMe2SiO
tionally,
we
have
previously
reported
that
1bα
2bα
1.6 : 1 (80%)
3.9 : 1 (99%)
(methylthio)alkynes are excellent substrates in
(Cp)2Zr(II) mediated coupling reactions.12 Curiously,
enynes bearing (alkylthio)alkyne substitution had not
1bβ
2bβ
Scheme 2
Synthesis 2000, No. 7, 1009–1019 ISSN 0039-7881 © Thieme Stuttgart · New York

1010
B. L. Pagenkopf et al.
PAPER
Table 1 Thermal Pauson-Khand Reaction of Stereogenic (Methylthio)-enynes with Catalytic Co2(CO)8
Entry
Substrate
Products
Yield (%)
MeO2C
MeO2C
MeO2C
MeO2C
MeO2C
MeO2C
O
O
X
X
X
1
2
3a, X = H
4a, X = SMe
3bb
4bb
1 : 6.0
1 : 12.3
3ba
4ba
39a
75a
O
O
TsN
Me
TsN
Me
TsN
Me
X
X
X
3
4
5a, X = H
6a, X = SMe
5bb
6bb
1.5 : 1
2.7 : 1
5ba
6ba
92b
93b
Me
Me
Me
Me
Me
Me
O
O
TsN
TsN
TsN
X
X
X
5
6
7a, X = H
8a, X = SMe
7bb
8bb
11.9 : 1
13.0 : 1
7ba
8ba
79a
80a
a 10 mol% Co2(CO)8.
b 5 mol% Co2(CO)8.
Some comparative Co(0) catalyzed cyclizations involving (78%) yield. These results, summarized in Scheme 3,
representative enynes and their terminal (methyl- clearly indicate that the stereoselectivity of cyclization
thio)alkynyl counterparts are illustrated in the Table. As is can be correlated with the size of the alkylthio substituent
evident from these results, the incorporation of a (methyl- and point to further synthetic advantages intrinsic to this
thio)alkynyl ether as a modifying cycloaddition compo- type of substrate modification.
nent usually, but not always, leads to an enhancement of
cyclization efficiency and/or diastereoselectivity. Note in
1 ATM CO
5 mol % Co2(CO)8
Me
O
Me
O
Me
O
entries 5 and 6 that the stereochemistry of the cis-olefin is
transferred to the product without isomerization. The abil-
ity of the Co(0) catalyzed PKR to cleanly translate alkene
geometry into product stereochemistry contrasts sharply
with the behavior of Ti(II) based catalyst systems.8 Fur-
thermore, no products were detected that may have result-
ed from isomerization prior to cyclization of precycles 7a
or 8a to the corresponding terminal olefin.
+
O
O
1,2-DME, 60 °C
X
X
X
9a, X = H
10a, X = SMe
11a, X = S(tBu)
(< 23%)
(81%)
(78%)
9bβ
10bβ
11bβ
5 : 1
12 : 1
42 : 1
9bα
10bα
11bα
Scheme 3
We next turned our attention to the effects caused by steric
modification of the thioalkyl substituent. To this end,
enyne 9a was subjected to the usual cyclization protocol
[5 mol% Co2(CO)8, CO (1 atmosphere), 1,2-DME, 60 °C]
to provide enones 9bb and 9ba with moderate diastereo-
selectivity (9bb/9ba = 5) albeit in poor (<23%) overall
yield. For the (methylthio)alkyne bearing substrate 10a, a
noteworthy improvement in both diastereoselectivity
(10bb/10ba = 12) and yield (81%) was observed. Impor-
tantly, for the corresponding (t-butylthio)alkyne 11a17 the
expected enones 11bb and 11ba were produced with out-
standing stereoselectivity (11bb/11ba = 42) and good
It is widely accepted that thioethers can serve as very ef-
fective ligands for transition metals.18 In a control experi-
ment, the ethoxyalkyne 12a was subjected to the Co(0)
catalyzed PKR (Scheme 4). Although the cyclization effi-
ciency remained gratifyingly high (84% yield) compared
to the terminal acetylene (<50%, Scheme 1), in this case
the normal stereoselectivity was reversed, and anomalous
preferential formation of the endo-product was observed
(12bb/12ba = 0.71).
Allenynes have recently emerged as viable substrates for
stoichiometric Pauson-Khand19a and related19b cycliza-
Synthesis 2000, No. 7, 1009–1019 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
(Alkylthio)alkynes as Addends in the Co(0) Catalyzed Intramolecular Pauson-Khand Reaction
1011
In conclusion, we have shown that the efficiencies and se-
lectivities of the Co(0) catalyzed PKR can be improved,
and many times markedly so, by substrate modification
via the simple expedient of alkyne sulfenylation. Applica-
tions of this strategy to problems of synthetic interest will
be described in future accounts from these laboratories.
1 ATM CO
5 mol % Co2(CO)8
Me
1,2-DME
60 °C, (84%)
Me
OEt
tBuMe2SiO
12a
Me
Me
+
O
O
Me
tBuMe2SiO
12bβ
Me
OEt
OEt
tBuMe2SiO
For general experimental procedures, see reference 20.
1 : 1.4
12bα
Representative Catalytic Pauson-Khand Reaction with
Co2(CO)8
Scheme 4
Procedure A
To a solution of dicobalt octacarbonyl (8.5 mg, 0.025 mmol, 5
mol%) in degassed 1,2-DME (5 mL) under a CO atm (balloon) was
added the enyne or dienyne (0.50 mmol) via a gas-tight syringe. Af-
ter 15-30 min, the resulting solution was heated to 60 °C in a con-
stant temperature bath until consumption of starting substrate was
observed by TLC. After cooling to r.t., brine and EtOAc were added
(1 mL each) and the biphasic mixture was stirred open to the atmo-
sphere for 30 min. Workup with EtOAc/brine (50:25 mL) and dry-
ing (Na2SO4) followed by evaporation of solvent and subsequent
purification by flash chromatography afforded the product. In some
instances, further purification was required and was accomplished
by passing a CH2Cl2 solution of substrate through a plug of neutral
Al2O3.
tions. In an experiment to determine whether allenynes
would be satisfactory substrates for the Co(0) catalyzed
PKR, 13a was found to afford the two possible dienones
13b and 13c in only 44% combined yield (13b/13c = 5.8)
along with the cross conjugated triene 13d (21%). In stark
contrast, analogous cyclization of 14a delivered 14b as
the exclusive dienone in 84% isolated yield (Scheme 5).
As further illustration of the cyclization efficiency en-
hancement for allenynes, carbonylative cycloaddition of
tosamide 15a provided dienone 15b in only 30% yield
whereas the cyclization of the corresponding methyl sul-
fide 16a secured 16b in 70% isolated yield.
Representative Catalytic Pauson-Khand Reaction with alkyne-
Co2(CO)6
Procedure B
Me
1 ATM CO
10 mol % Co2(CO)8
To a solution of 2-methyl-3-butyn-2-ol hexacarbonyldicobalt (9.2
mg, 0.025 mmol, 5 mol%) in degassed 1,2-DME (5 mL) under a CO
atm (balloon) was sequentially added Et3SiH (50 mL of a 0.5 M so-
lution in p-xylene, 0.025 mmol) and cyclohexylamine (9 mL, 0.075
mmol). The resulting solution was heated at 65 °C for 15 min at
which time the enyne or dienyne (0.50 mmol) was added via a gas-
tight syringe. The resulting solution was maintained at 65 °C for 6
h, subsequently cooled to r.t. and processed as described in Proce-
dure A.
Me
MeO2C
MeO2C
1,2-DME, 60 °C
13a
Me
Me
Me
Me
O
MeO2C
MeO2C
MeO2C
MeO2C
+
O
5.8 : 1 (44%)
Me
13b
13c
4,4-Dimethyl-5-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-7-
methylthiohept-1-en-6-yne (2a)
a) LDA
b) MeSCN
(84%)
To a solution of alkyne 1a (315 mg, 1.2 mmol) in THF (3 mL) was
added a -20 °C, a solution of LDA•THF (2.04 mL, 0.67 M solution
in methylcyclohexane, 1.1 equiv). After stirring for 30 min,
CH3SCN (97 mL, 1.15 equiv) was added neat and the resulting so-
lution was allowed to warm to r.t. and was stirred overnight. The so-
lution was subsequently treated with half-sat. NaHCO3 (10 mL) and
the resulting mixture was extracted with Et2O (3 ¥ 10 mL). The
combined organic phases were washed with H2O (5 mL), brine (5
mL), dried (MgSO4), filtered and concentrated in vacuo. The resi-
due was subjected to flash chromatography on silica gel (hexane) to
afford 234 mg (63%) of the title compound as an air-sensitive yel-
low oil.
MeO2C
MeO2C
13d (21%)
Me
Me
Me
Me
1 ATM CO
10 mol % Co2(CO)8
MeO2C
MeO2C
MeO2C
MeO2C
O
1,2-DME, 60 °C
SMe
(84%)
SMe
14a
14b
Scheme 5
IR (thin film): n = 3075, 2186, 1639, 1091, 837 cm-1.
1H NMR (CDCl3): d = 5.86-5.73 (m, 1H), 5.03-4.98 (m, 2H), 4.08
(s, 1H), 2.35 (s, 3H), 2.14-2.00 (m, 2H), 0.88 (s with fine structure,
15H), 0.12 (s, 3H), 0.07 (s, 3H).
13C NMR (CDCl3): d = 135.2 (CH), 117.1 (CH2), 93.4 (C), 71.4
(CH), 42.7 (CH2), 39.4 (C), 25.8 (CH3), 22.8 (CH3), 22.7 (CH3),
19.0 (CH3), 18.2 (C), -4.2 (CH3), -5.1 (CH3).
Me
Me
Me
Me
O
1 ATM CO
catalytic Co2(CO)8
TsN
TsN
1,2-DME, 60 °C
X
X
15a, X = H
16a, X = SMe
10 mol % Co2(CO)8
5 mol % Co2(CO)8
15b (30%)
16b (70%)
HRMS: m/z calcd for C6H30O2SiS (M+) 326.1736. Found:
326.1733.
Scheme 6
Synthesis 2000, No. 7, 1009–1019 ISSN 0039-7881 © Thieme Stuttgart · New York

1012
B. L. Pagenkopf et al.
PAPER
trans-5,5-Dimethyl-4-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-3-
methylthio-4,5,6,6a-tetrahydro-2(1H)-pentalenone (2bb)
Enyne 2a (75 mg, 0.25 mmol) was cyclized according to general
Procedure A except that 10 mol% Co2(CO)8 was employed to afford
80 mg (98%) of a 3.9:1 diastereomeric mixture of bicyclopenten-
ones 2bb and 2ba as determined by GC analysis of the crude reac-
tion mixture.
H2O (30 mL), and extracted with EtOAc (3 ¥ 30 mL). The com-
bined organic layers were washed with sat. NaHCO3 (20 mL), brine
(3 ¥ 30 mL), dried (MgSO4), filtered and concentrated in vacuo.
Bulb to bulb distillation (190 °C/14 mmHg) followed by column
chromatography on silica (0-2% EtOAc in hexanes) gave the enyne
as a clear colorless oil (0.94 g, 75%).
IR (NaCl, film): n = 3287, 3056, 2952, 2840, 2122, 1732, 1435
2bb: Rf = 0.45 (10% EtOAc/hexanes).
IR (thin film): n = cm-1.
1H NMR (CDCl3): d = 4.19 (s, 1H), 3.11-3.21 (m, 1H), 2.72 (dd,
J = 17.9, 6.8 Hz, 1H), 2.33 (s, 3H), 2.08-2.01 (m, 2H), 1.10 (s, 3H),
1.06 (dd, J = 13.0, 6.6 Hz, 1H), 0.85 (s, 9H), 0.81 (s, 3H), 0.11 (s,
3H), 0.02 (s, 3H).
13C NMR (CDCl3): d = 207.2 (C), 183.8 (C), 130.6 (C), 76.9 (CH),
45.0 (C), 44.7 (CH2), 42.9 (CH2), 39.8 (CH), 28.9 (CH3), 25.7
(CH3), 23.8 (CH3), 18.1 (C), 14.4 (CH3), -4.5 (CH3), -4.9 (CH3).
cm-1.
1H NMR (300 MHz, CDCl3): d = 5.76 (d with fine structure,
J = 10.6 Hz, 1H), 5.69 (d with fine structure, J = 10.6 Hz, 1H), 3.75
(s, 3 H), 3.71 (s, 3H), 3.14-3.04 (m, 1H), 2.88 (dd, J = 2.7, 17.2 Hz,
1H), 2.80 (dd, J = 2.7, 17.2 Hz, 1H), 2.00 (t, J = 2.7 Hz, 1H), 1.98-
1.91 (m, 2H), 1.8-1.73 (m, 2H), 1.64-1.47 (m, 1H), 1.42-1.27 (m,
1H).
13C NMR (75 MHz, CDCl3): d = 170.17 (C), 169.98 (C), 129.1
(CH), 127.2 (CH), 79.4 (C), 71.2 (CH), 60.3 (C), 52.43 (CH3), 52.24
(CH3), 38.9 (CH), 24.75 (CH2), 24.18 (CH2), 22.39 (CH2), 22.16
(CH2).
HRMS: m/z for C17H30O2SiS (M+) 326.1736. Found: 326.1736.
HRMS: m/z calcd for C14H18O4 (M+) 250.1205. Found: 250.1211.
The assigned stereochemistry is consistent with the following ob-
served NOE data.
4a-syn-7a-syn-4,4-Bis(methoxycarbonyl)-3,4,4a,5,6,7,7a,7b-oc-
tahydrocyclopenta[c,d]inden-1-one (3ba)
Enyne 3a (125 mg, 0.50 mmol) was cyclised according to procedure
A, affording 54 mg (39%) of a 6.0:1 mixture of enones after 12 h.
H
0%
O
IR (thin film): n = 2963, 2850, 1728, 1699, 1627, 1435, 1398, 1252,
H
SCH3
1234 cm-1.
tBuMe2SiO
1H NMR (CDCl3): d = 5.81 (m, 1H), 3.75 (s, 6H), 3.60 (d with fine
structure, J = 20.6 Hz, 1H), 3.33 (m, 1H), 3.20 (d, J = 20.6 Hz, 1H),
2.94 (m, 1H), 2.60 (dt, J = 18.7, 9.4 Hz, 1H), 2.01 (m, 1H), 1.63 (m,
1H), 1.40 (m, 1H), 1.10 (m, 1H), 0.90 (m, 1H), 0.60 (m, 1H).
13C NMR (CDCl3): d = 213.5 (C), 183.4 (C), 172.3 (C), 169.8 (C),
123.5 (C), 66.2 (C), 53.5 (CH3), 53.2 (CH3), 49.8 (CH), 46.6 (CH),
42.3 (CH), 34.5 (CH2), 25.5 (CH2), 23.6 (CH2), 23.2 (CH2).
cis-5,5-Dimethyl-4-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-3-
methylthio-4,5,6,6a-tetrahydro-2(1H)-pentalenone (2ba)
Rf = 0.23 (10% EtOAc/hexanes).
IR (thin film): n = 1711, 1620, 1249, 1132, 838 cm-1.
1H NMR (CDCl3): d = 4.58 (s, 1H), 2.92-2.83 (m, 1H), 2.70 (dd,
J = 17.1, 7.0 Hz,1 H), 2.32 (s, 3H), 2.08 (dd, J = 17.7, 3.5 Hz,1 H),
1.94 (dd, J = 13.1, 10.0 Hz, 1H), 1.28 (dd, J = 13.1, 8.2 Hz,1 H),
1.14 (s, 3H), 0.95 (s, 9H), 0.85 (s, 3H), 0.19 (s, 3H), 0.10 (s, 3H).
13C NMR (CDCl3): d = 206.6 (C), 183.8 (C), 130.5 (C), 80.3 (CH),
44.1 (CH2), 43.6 (CH2), 36.3 (CH), 29.6 (C), 28.7 (CH3), 26.1
(CH3), 24.6 (CH3), 18.2 (C), 15.0 (CH3), -4.1 (CH3), -4.3 (CH3).
HRMS: m/z calcd for C15H18O5 (M+) 278.1154. Found: 278.1158.
4a-syn-7a-syn-4,4-Bis(methoxycarbonyl)-2-methylthio-
3,4,4a,5,6,7,7a,7b-octahydrocyclopenta[c,d]inden-1-one (4ba)
Enyne 4a (148 mg, 0.50 mmol) was cyclized according to proce-
dure A, affording 122 mg (75%) of a 12.3:1 mixture of enones after
12 h.
HRMS: m/z calcd for C17H30O2SSi (M+) 326.1736. Found:
326.1730.
IR (thin film): n = 2932, 1762, 1718, 1589, 1478, 1291, 1154 cm-1.
1H NMR (CDCl3): d = 3.75 (s, 3H), 3.74 (s, 3H), 3.60 (dd, J = 20.9,
2.6 Hz, 1H), 3.29 (br m, 1H), 3.10 (d, J = 20.9 Hz, 1H), 2.93 (m,
1H), 2.70 (m, 1H), 2.37 (s, 3H), 2.05 (m, 1H), 1.60 (m, 1H), 1.30
(m, 1H), 1.10 (m, 1H), 0.90 (m, 1H), 0.60 (m, 1H).
The assigned stereochemistry is consistent with the following ob-
served NOE data.
13C NMR (CDCl3): d = 209.1 (C), 178.5 (C), 172.2 (C), 169.7 (C),
129.9 (C), 66.0 (C), 53.6 (CH3), 53.2 (CH3), 48.3 (CH), 46.1 (CH),
42.3 (CH), 34.5 (CH2), 25.4 (CH2), 23.5 (CH2), 23.2 (CH2), 14.5
(CH3).
H
4.4%
3.9%
O
HRMS: m/z calcd for C16H20O5S (M+) 324.1031. Found: 324.1029.
H
SMe
tBuMe2SiO
1-Methyl-2-[(4-methylbenzene)sulfonyl]-2,3,3a,4-tetrahydro-
1H-cyclopenta[c]pyrrol-5-one (5b)
The title compound was prepared from 5a21 as a mixture of diaste-
reomers (2.1:1) in 92% yield using Procedure A (12 h). The title
compound was prepared as a mixture of diastereomers (1.9:1) in
77% yield using Procedure B (12 h). Purification by flash chroma-
tography (SiO2, 15% EtOAc in hexanes to 40% EtOAc gradient for
elution) afforded the title compound as a colorless, viscous oil.
Dimethyl 2-(2-Propynyl)-2-(2-cyclohexenyl)propan-1,3-dioate
(3a)
A solution of dimethyl 2-(2-cyclohexenyl)propan-1,3-dioate (1.06
g, 5.0 mmol) in DMF (10 mL) was added dropwise to a cooled
(0 °C) suspension of sodium hydride (300 mg, 7.5 mmol, 1.5 equiv,
60% disp.) in DMF (5 mL) via cannula. The yellow suspension was
then stirred at r.t. for 1 h, recooled to 0 °C, and propargyl bromide
(565 mL, 7.5 mmol, 1.5 equiv) was added. The mixture was allowed
to attain r.t. and stirred overnight. The suspension was poured into
IR (thin film): n = 3409 (m), 2978 (m), 2930 (m), 1716 (br s), 1652
(s), 1343 (br s), 1163 (br s), 1093 (s), 819 (s), 667 (s) cm-1.
Synthesis 2000, No. 7, 1009–1019 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
(Alkylthio)alkynes as Addends in the Co(0) Catalyzed Intramolecular Pauson-Khand Reaction
1013
7.3%
1H NMR (300 MHz, CDCl3): d = 7.68 (d, J = 7.7 Hz, 2H), 7.61 (d,
J = 7.7 Hz, 2H), 7.25 (approx. d, J = 7.7 Hz, 4H), 5.88 (s, 1H), 5.76
(s, 1H), 4.46 (q, J = 6.7 Hz, 1H), 4.22 (q, J = 6.7 Hz, 1H), 3.94 (ap-
prox. t, J = 10.2 Hz, 1H), 3.87 (approx. t, J = 8.4 Hz, 1H), 3.32 (m,
1H), 2.87 (approx. t, J = 11.6 Hz, 1H), 2.51 (dd, J = 17.9, 6.5 Hz,
1H), 2.42-2.38 (m, 2H), 2.34 (br s, 6H), 1.96 (m, 1H), 1.95 (m, 2H),
1.52 (d, J = 6.7 Hz, 3H), 1.48 (d, J = 6.7 Hz, 3H).
8.6%
Ha
3.1%
29.5%
26.7%
Hd
Ha
Hd
Hc
Hc
5.4%
TsN
O
TsN
O
1.1%
Hb
Hb
He
He
Me
Me
2.5%
13C NMR (75.5 MHz, CDCl3): d = 207.4 (2 ¥ C), 185.5 (C), 182.8
(C), 143.94 (C), 143.81 (C), 135.3 (C), 132.7 (C), 129.90 (2 ¥ CH),
129.73 (2 ¥ CH), 127.4 (2 ¥ CH), 126.9 (2 ¥ CH), 125.5 (CH),
124.1 (CH), 55.3 (CH), 55.2 (CH), 53.2 (CH2), 51.7 (CH2), 42.9
(CH), 41.1 (CH), 40.0 (CH2), 39.5 (CH2), 22.0 (CH3), 21.3
(2 ¥ CH3), 20.3 (CH3).
IR (NaCl, thin film): n = 2929 (w), 1742 (s), 1338 (s), 1161 (s), 1090
(m) cm-1.
1H NMR (300 MHz, CDCl3): d = 7.70 (d, J = 8.1 Hz, 2H), 7.32 (d,
J = 8.1 Hz, 2H), 3.67 (q, J = 6.6 Hz, 1H), 3.58 (dd, J = 11.4, 8.7 Hz,
1H), 3.16 (dd, J = 11.4, 8.7 Hz, 1H), 2.74 (m, 1H), 2.52 (m, 1H),
2.42 (s, 3H), 2.31-2.23 (m, 2H), 2.14 (dd, J = 19.0, 3.4 Hz, 1H),
1.41-1.35 (obscured peak, 1H), 1.34 (d, J = 6.6 Hz, 3H).
13C NMR (62.9 MHz, CDCl3): d = 216.0 (C), 143.7 (C), 134.2 (C),
129.8 (2 ¥ CH), 127.5 (2 ¥ CH), 58.3 (CH2), 53.6 (CH2), 45.0 (CH),
42.0 (CH2), 38.3 (CH2), 37.5 (CH), 21.5 (CH3), 18.4 (CH3).
Major diastereomer: HRMS (EI): m/z calcd for C15H17NO3S
(291.0930). Found: 291.0929.
Minor diastereomer: HRMS (EI): m/z calcd for C15H17NO3S (M+)
291.0933. Found: 291.0929.
exo-1-Methyl-2-[(4-methylbenzene)sulfonyl]hexahydro-1H-cy-
clopenta[c]pyrrol-5-one (17b) and endo-1-Methyl-2-[(4-methyl-
benzene)sulfonyl]hexahydro-1H-cyclopenta[c]pyrrol-5-one
(17a)
A solution of endo- and exo-1-methyl-2-[(4-methylbenzene)sulfo-
nyl]-2,3,3a,4-tetrahydro-1H-cyclopenta[c]pyrrol-5-one (5b) (0.129
g, 0.443 mmol, 1.00 equiv, 1.5:1 mixture of diastereomers) and
Pd(OH)2 (13 mg of 20% Pd(OH)2 on C) in EtOAc (1.5 mL) under
an atmosphere of H2 was allowed to stir 2 h. Filtration of the sus-
pension through Celite and concentration afforded 0.126 g of the ti-
tle compounds. Analysis of the crude residue by 1H NMR revealed
a 1.5:1 mixture of diastereomers. Purification by flash chromatog-
raphy (basic Al2O3, 13 ¥ 2 cm, 5% EtOAc in hexanes to 25%
EtOAc in hexanes gradient for elution) afforded 17b and 17a.
HRMS (EI): m/z calcd for C14H16NO3S (M-CH3)+ 293.1086.
Found: 293.1084.
The stereochemical assignment was based on the following NOE
data determined at 500 MHz (CDCl3).
5.0%
H
H
H
3.4%
TsN
Me
O
TsN
Me
O
H
H
H
4.6%
3.7%
8.7%
8.8%
H2, Pd(OH)2
+
TsN
Me
O
TsN
Me
O
TsN
Me
O
N-(1-Methyl-3-(methylthio)prop-2-ynyl)-N-(2-propenyl)-4-me-
thylbenzenesulfonamide (6a)
17β
5b
17α
To a solution of N-(1-methylprop-2-ynyl)-N-(2-propenyl)-4-meth-
ylbenzenesulfonamide (5a) (0.631 g, 2.40 mmol, 1.00 equiv) in
THF (6 mL) at -78 °C was added n-BuLi (1.6 mL of a 1.6 M solu-
tion in hexanes, 2.52 mmol, 1.05 equiv) over 5 min. The resulting
solution stirred for 5 min at -78 °C at which time MeSCN (189 mL,
2.76 mmol, 1.15 equiv) was added dropwise. The resulting suspen-
sion was stirred for 1 h at -78 °C and then was quenched by the ad-
dition of sat. NH4Cl (3 mL) and allowed to warm to r.t. The reaction
mixture was poured into EtOAc and H2O (30:25 mL). The organic
phase was washed with H2O (25 mL), brine (25 mL), and dried
(MgSO4). Evaporation of solvent and purification by flash chroma-
tography (SiO2, hexanes to 10% EtOAc in hexanes gradient for elu-
tion) afforded 1.0 g (85%) of the title compound as a pale yellow
semi-solid.
exo-1-Methyl-2-[(4-methylbenzene)sulfonyl]-2,3,3a,4-tetrahy-
dro-1H-cyclopenta[c]pyrrol-5-one (17b)
Major diastereomer, less polar
1H NMR (300 MHz, CDCl3): d = 7.68 (d, J = 8.2 Hz, 2H), 7.29 (d,
J = 8.2 Hz, 2H), 3.76 (dd, J = 10.0, 7.2 Hz, 1H), 3.50 (dq, J = 6.4,
3.4 Hz, 1H), 3.00 (m, 1H), 2.90 (dd, J = 10.0, 7.2 Hz, 1H), 2.47 (m,
1H), 2.41 (s, 3H), 2.28 (approx. d, J = 8.5 Hz, 1H), 2.21 (approx. d,
J = 8.5 Hz, 1H), 1.79 (dd, J = 19.1, 3.4 Hz, 1H), 1.40-1.23 (ob-
scured peak, 1H), 1.39 (d, J = 6.4 Hz, 3H).
13C NMR (62.9 MHz, CDCl3): d = 216.5 (C), 143.8 (C), 134.2 (C),
129.8 (2 ¥ CH), 127.3 (2 ¥ CH), 61.3 (CH), 52.9 (CH2), 47.6 (CH),
41.5 (CH2), 41.1 (CH2), 37.6 (CH), 22.3 (CH3), 21.6 (CH3).
IR (NaCl, thin film): n = 3081 (w), 2985 (m), 2930 (m), 2870 (w),
2173 (m), 1344 (s), 1167 (s), 1008 (br m), 668 (s), 566 (s) cm-1.
1H NMR (300 MHz, CDCl3): d = 7.64 (d, J = 8.2 Hz, 2H), 7.22 (d,
J = 8.2 Hz, 2H), 5.84 (m, 1H), 5.41 (approx. dt, J = 17.1, 1.4 Hz,
1H), 5.04 (approx. dt, J = 10.2, 1.4 Hz, 1H), 4.87 (approx. q, J = 7.1
Hz, 1H), 3.84 (m, 1H), 3.62 (m, 1H), 2.33 (s, 3H), 2.05 (s with fine
structure, 3H), 1.33 (d with fine structure, J = 7.1 Hz, 3H).
IR (NaCl, thin film): n = 2966 (w), 2928 (w), 2851 (w), 1742 (s),
1341 (m), 1091 (s) cm-1.
HRMS (EI): m/z calcd for C14H16NO3S (M-CH3)+ 278.1086.
Found: 278.1084.
13C NMR (75.5 MHz, CDCl3): d = 143.1 (C), 135.95 (CH), 135.68
(C), 129.2 (2 ¥ CH), 127.4 (2 ¥ CH), 116.7 (CH2), 89.6 (C), 76.6
(C), 47.17 (CH), 47.14 (CH2), 22.3 (CH3), 21.2 (CH3), 18.5 (CH3).
The stereochemical assignment was based on the following NOE
data determined at 500 MHz (CDCl3).
endo-1-Methyl-2-[(4-methylbenzene)sulfonyl]-2,3,3a,4-tetrahy-
dro-1H-cyclopenta[c]pyrrol-5-one (17a)
Minor diastereomer, more polar
HRMS (EI): m/z calcd for C15H19NO2S2 (M+) 309.0855. Found:
309.0857.
Synthesis 2000, No. 7, 1009–1019 ISSN 0039-7881 © Thieme Stuttgart · New York

1014
B. L. Pagenkopf et al.
PAPER
1-Methyl-2-[(4-methylbenzene)sulfonyl]-7-methylthio-2,3,3a,4-
tetrahydro-1H-cyclopenta[c]pyrrol-5-one (6b)
13C NMR (75 MHz, CDCl3): d = 149.8 (C), 144.1 (C), 137.1 (C),
129.1 (CH), 127.6 (CH), 84.7 (C), 82.2 (C), 71.3 (CH), 44.9 (CH),
27.7 (CH3), 21.77 (CH3), 21.44 (CH3).
The title compound was prepared as a mixture of diastereomers
(2.7:1) in 93% yield using Procedure A (12 h). The title compound
was prepared as a mixture of diastereomers (2.6/1) in 90% yield us-
ing Procedure B (12 h). Purification by flash chromatography (SiO2,
15% EtOAc in hexanes to 40% EtOAc gradient for elution) afford-
ed the title compound as a colorless, viscous oil. Further purifica-
tion by flash chromatography (SiO2, 5% EtOAc to 25% EtOAc in
hexanes gradient for elution) afforded 6bb, (major diastereomer,
less polar).
EIMS (CI/NH3): m/z = 341 (M+NH4 , 5%), 324 (M+H+, 1%), 285
+
(100%).
HRMS (PCI/NH3): m/z calcd for C16H21NO4S (M+H+) 324.1270.
Found: 324.1258.
N-2-(Pent-3-ynyl)-4-methylbenzenesulfonamide
Butyllithium (8.14 mL, 21.0 mmol, 2.58 M in hexanes, 1.05 equiv)
was added to a solution of N-2-(but-3-ynyl)-N-(2-methyl-2-propyl-
oxycarbonyl)-4-methylbenzenesulfonamide (6.47 g, 20.0 mmol) in
THF (40 mL) at -78 °C over 5 min. After 30 min at -78 °C, methyl
iodide (1.49 mL, 24 mmol, 1.2 equiv) was added dropwise, fol-
lowed by HMPA (6.96 mL, 40 mmol, 2 equiv) dropwise. The
solution was stirred at -78 °C for 1 h and then allowed to attain r.t.
The mixture was poured into H2O (50 mL), extracted with EtOAc
(3 ¥ 50 mL), and the combined organic layers were washed with
sat. CuSO4 (30 mL), brine (30 mL), dried (MgSO4), filtered and
concentrated to a yellow oil. Column chromatography on silica (0-
5% EtOAc in hexanes) gave a pale yellow oil (6.46 g). A portion of
this oil (3.10 g, 9.19 mmol) in DMSO (50 mL) was heated to reflux
for 20 min. The cooled solution was poured into H2O (50 mL) and
the mixture extracted with EtOAc (3 ¥ 40 mL). The combined or-
ganic layers were washed with H2O (50 mL), sat. NaHCO3 (30 mL),
brine (50 mL), dried (MgSO4), filtered and concentrated. The resi-
due was purified by chromatography on silica gel (0-12.5% EtOAc
in hexanes) to afford the title compound as an off-white solid. Re-
crystallisation from CH2Cl2/hexane (10:30 mL) gave fine white
needles (2.04 g, 90% over 2 steps); mp 128.7-129.8 °C.
IR (NaCl, thin film): n = 2977 (w), 2927 (w), 1714 (br m), 1343 (br
m), 1162 (s) cm-1.
1H NMR (300 MHz, CDCl3): d = 7.70 (d, J = 8.1 Hz, 2H), 7.32 (d,
J = 8.1 Hz, 2H), 4.38 (q, J = 6.5 Hz, 1H), 3.90 (approx. t, J = 8.2
Hz, 1H), 3.28 (m, 1H), 2.65 (dd, J = 17.8, 6.5 Hz, 1H), 2.46-2.38
(obscured peak, 1H), 2.42 (s, 3H), 2.30 (s, 3H), 2.04 (dd, J = 17.8,
3.4 Hz, 1H), 1.56 (d, J = 6.5 Hz, 3H).
13C NMR (62.9 MHz, CDCl3): d = 203.9 (C), 176.0 (C), 144.1 (C),
133.2 (C), 130.9 (C), 129.9 (2 ¥ CH), 127.7 (2 ¥ CH), 55.5 (CH2),
53.3 (CH2), 39.76 (CH), 39.70 (CH), 21.6 (2 ¥ CH3), 13.8 (CH3).
HRMS (EI): m/z calcd for C16H19NO3S2 (337.0800). Found:
337.0806.
Minor diastereomer: HRMS (EI): m/z calcd for C16H19NO3S2 (M+)
337.0803. Found: 337.0806.
The stereochemical assignment of the major diastereomer was
based on the following GOESY data (mixing time = 800 msec) de-
termined at 250 MHz (CDCl3).
1H NMR (300 MHz, CDCl3): d = 7.78 (d, J = 8.2 Hz, 2H), 7.29 (d,
J = 8.2 Hz, 2H), 4.70 (d, J = 8.5 Hz, 1H), 4.18-4.04 (m, 1H), 2.41
(s, 3H), 1.51 (d, J = 2.2 Hz, 3H), 1.35 (d, J = 6.9 Hz, 3H).
13C NMR (75 MHz, CDCl3): d = 143.1 (C), 137.4 (C), 129.2 (CH),
127.3 (CH), 79.7 (C), 78.1 (C), 41.4 (CH), 23.3 (CH3), 21.3 (CH3),
3.0 (CH3).
EIGCMS: m/z = 237 (M+, 0.4%), 222 (M+-Me, 100%).
HRMS: m/z calcd for C12H15NO2S (M+) 237.0824. Found:
4.3%
3.7%
Hb
TsN
Me
3.3%
3.9%
Hb
Hd
Hd
Hc
Hc
O
TsN
Ha
2.3%
O
1%
1%
Me
SMe
SMe
237.0817.
N-2-(cis-Pent-3-enyl)-4-methylbenzenesulfonamide
N-2-(But-3-ynyl)-N-(2-methyl-2-propyloxycarbonyl)-4-methyl-
benzenesulfonamide
NaBH4 (130 mL, 0.13 mmol, 1M in 95:5 EtOH/2M NaOH, 0.03
equiv) was added dropwise to
a degassed solution of
Diisopropylazodicarboxylate (11.8 mL, 60 mmol, 1.2 equiv) was
added dropwise via addition funnel, over 50 min, to a solution of N-
t-butoxycarbonyl-p-toluenesulfonamide (13.57 g, 50 mmol), Ph3P
(15.7 g, 60 mmol, 1.2 equiv) and 2-but-3-ynol (4.70 mL, 60 mmol,
1.2 equiv) in THF (130 mL) at 0 °C under Ar. The mixture was
stirred at 0 °C for a further 10 min and then allowed to warm rapidly
to ambient temperature. After 30 min at r.t., the mixture was con-
centrated in vacuo to a brown red oil. The mixture was placed under
high vacuum (100 m) for 4 h. Et2O (200 mL) was added and the mix-
ture was stirred for 30 min, before addition of hexane (200 mL). The
resultant suspension was filtered, the filter cake washed with Et2O/
hexane (1:1, 200 mL), and the filtrate concentrated to a light brown-
orange pasty solid. Column chromatography on silica (0-5%
EtOAc in hexanes) gave a pale yellow oil. Recrystallisation from
Et2O/hexane afforded the title compound as white prisms (14.76 g,
91%); mp 70.4-73.2 °C.
Ni(OAc)2.4H2O in EtOH (10 mL) to give a black suspension. Eth-
ylene diamine (28 mL, 0.42 mmol, 0.04 equiv) was added followed
by a solution of N-2-(pent-3-ynyl)-4-methylbenzenesulfonamide
(997 mg, 4.20 mmol) in EtOH (40 mL), quantitatively transferred
with further EtOH (10 mL). The flask was purged with H2 and the
mixture stirred under an atm of H2 for 4.5 h. The mixture was fil-
tered through a pad of Celite layered over silica, the filter cake
washed with EtOAc, and the filtrate concentrated in vacuo. Column
chromatography on silica (0-15% EtOAc in hexanes) and 10%
AgNO3/SiO2 (0-10% EtOAc in hexanes) gave the title compound
as a pale yellow solid (718 mg, 76%); mp 55.3-57.1 °C (needles
from Et2O/hexanes, 1:10).
1H NMR (300 MHz, CDCl3): d = 7.74 (d, J = 8.3 Hz, 2H), 7.27 (d,
J = 8.3 Hz, 2H), 5.32 (ddq, J = 0.9, 10.8, 6.9 Hz, 1H), 5.11 (approx.
tq, J = 9.1, 1.7 Hz, 1H), 4.55 (br s, 1H), 4.25-4.08 (m, 1H), 2.41 (s,
3H, 1.44 (dd, J = 1.7, 6.9 Hz, 3H), 1.16 (d, J = 6.6 Hz, 3H).
13C NMR (75 MHz, CDCl3): d = 143.0 (C), 138.0 (C), 131.5 (CH),
129.3 (CH), 127.1 (CH), 125.3 (CH), 46.6 (CH), 22.2 (CH3), 21.4
(CH3), 12.7 (CH3);
IR (KBr disc): n = 3277, 2982, 2940, 2121 (w), 1738, 1733, 1598,
1360, 1152 cm-1.
1H NMR (300 MHz, CDCl3): d = 7.85 (d, J = 8.2 Hz, 2H), 7.30 (d,
J = 8.2 Hz, 2H), 5.47 (dq, J = 2.5, 7.0 Hz, 1H), 2.43 (s, 3H), 2.37 (d,
J = 2.5 Hz, 1H), 1.74 (d, J = 7.0 Hz, 3H), 1.35 (s, 9H).
HRMS: m/z calcd for C12H17NO2S (M+) 239.0980. Found:
239.0976.
Synthesis 2000, No. 7, 1009–1019 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
(Alkylthio)alkynes as Addends in the Co(0) Catalyzed Intramolecular Pauson-Khand Reaction
1015
N-2-(cis-Pent-3-enyl)-N-2-propynyl-4-methylbenzenesulfon-
amide (7a)
(s, 3H), 2.24 (s, 3H), 1.58 (d, J = 5.6 Hz, 3H), 1.23 (d, J = 6.9 Hz,
3H).
A 25 mL flask was charged with N-2-(cis-pent-3-enyl)-4-methyl-
benzenesulfonamide (700 mg, 2.93 mmol), anhyd K2CO3 (1.21 g,
8.78 mmol, 3 equiv) and DMF (10 mL). Propargyl bromide (660
mL, 8.78 mmol, 3 equiv) was added to the stirred suspension. After
3.5 h, the mixture was poured into H2O (40 mL), and extracted with
EtOAc (3 ¥ 20 mL). The organic layers were washed with brine
(3 ¥ 30 mL), dried (MgSO4), filtered and concentrated to an orange
oil. Column chromatography on silicagel (0-5% EtOAc in hex-
anes) gave the title compound as a pale yellow oil (789 mg, 97%).
13C NMR (75 MHz, CDCl3): d = 142.8 (C), 137.8 (C), 129.0 (CH),
128.95 (CH), 127.33 (CH), 127.21 (CH), 88.8 (C), 75.8 (C), 50.0
(CH), 33.8 (CH2), 21.3 (CH3), 19.9 (CH3), 18.4 (CH3), 12.8 (CH3).
MS (EI): m/z = 323 (M+, 7%), 293 (100%).
HRMS: m/z calcd for C16H21NO2S2 (M+) 323.1014. Found:
323.1005.
3-Methyl-4-methyl-2-[(4-methylbenzene)sulfonyl]-6-methyl-
thio-2,3,3a,4-tetrahydro-1H-cyclopenta[c]pyrrol-5-one (8bb)
The title compound was prepared from 8a (81 mg, 0.25 mmol) to
afford the enones 70 mg (80%) as a mixture of diastereomers
(13.0:1) using Procedure A (12 h) except that 10 mol% Co2(CO)8
was used.
IR (KBr disc): n = 3278, 3022, 2978, 2931, 2876, 2121, 1655, 1598,
1333, 1153 cm-1.
1H NMR (300 MHz, CDCl3): d = 7.78 (approx. dt, J = 8.2, 1.9 Hz,
2H), 7.26, (d, J = 8.2 Hz, 2H), 5.57-5.41 (m, 2H), 4.83 (approx.
pentet, J = 7.1 Hz, 1H), 4.14 (dd, J = 2.5, 18.6 Hz, 1H), 4.07 (dd,
J = 2.5, 18.6 Hz, 1H), 2.41 (s, 3H), 2.15 (t, J = 2.5 Hz, 1H), 1.57 (d
with fine structure, J = 5.2 Hz, 3H), 1.26 (d, J = 6.9 Hz, 3H).
13C NMR (75 MHz, CDCl3): d = 143.0 (C), 137.7 (C), 129.1 (CH),
128.8 (CH), 127.3 (CH), 127.3 (CH), 79.9 (C), 72.4 (CH), 50.2
(CH), 32.5 (CH2), 21.3 (CH3), 19.9 (CH3), 12.8 (CH3).
IR (NaCl, thin film): n = 2968 (m), 2928 (m), 1711 (s), 1643 (m),
1597 (m), 1454 (m), 1346 (s), 1160 (br s), 1090 (s), 1040 (m), 817
(m), 716 (m), 655 (s) cm-1.
1H NMR (300 MHz, CDCl3): d = 7.68 (d, J = 8.1 Hz, 2H), 7.30 (d,
J = 8.1 Hz, 2H), 4.35-4.21 (m, 2H), 3.10 (m, 1H), 2.93 (m, 1H),
2.62 (dq, J = 14.6, 7.6 Hz, 1H), 2.39 (s, 3H), 2.24 (s, 3H), 1.53 (d,
J = 6.0 Hz, 3H), 0.84 (d, J = 7.6 Hz, 3H).
13C NMR (62.9 MHz, CDCl3): d = 207.1 (C), 167.8 (C), 144.0 (C),
133.8 (C), 129.8 (2 ¥ CH), 127.48 (2 ¥ CH), 127.42 (C), 56.7 (CH),
54.1 (CH), 49.7 (CH2), 42.2 (CH), 21.5 (2 ¥ CH3), 14.2 (CH3), 13.0
(CH3).
MS (EI): m/z = 277 (M+, 2%), 262 (M+-Me, 94%), 91 (100%).
HRMS: m/z calcd for C15H19NO2S (M+) 277.1137. Found:
277.1139.
2,3,3a,4-Tetrahydro-2-((4-methylphenyl)sulfonyl)-3-exo-,4-
endo-dimethylcyclopenta[c]pyrrol-5(1H)-one (7bb)
The title compound was prepared from 7a (139 mg, 0.50 mmol) to
afford the enones 121 mg (79%) as a mixture of diastereomers
(13.0:1) using Procedure A (12 h) except that 10 mol% Co2(CO)8
was used. Recrystallisation from Et2O/hexane gave the major dia-
stereomer as a white solid; mp 97.0-98.2 ºC.
HRMS (EI): m/z calcd for C17H21NO3S2 (M+) 351.0963. Found:
351.0963.
The indicated stereochemistry is consistent with the following NOE
data.
IR (thin film): n = 2969, 2932, 1709, 1651, 1344, 1163, 1090, 1040,
5.4%
4.1%
4.7%
684, 664 cm-1.
1H NMR (CDCl3): d =7.67 (d, J = 8.2 Hz, 2H), 7.67 (d, J = 8.2 Hz,
2H), 5.76 (br s, 1H), 4.37 (d, J = 16.9 Hz, 1H), 4.19 (d, J = 16.9 Hz,
1H), 3.16 (m, 1H), 3.02 (m, 1H), 2.57 (m, 1H), 2.41 (s, 3H), 1.58 (d,
J = 5.9 Hz, 3H), 0.88 (d, J = 7.7 Hz, 3H).
9.2%
5.2%
7.6%
Me
H
Me
H
H
H
H
Me
H
Me
TsN
O
TsN
O
13C NMR (CDCl3): d = 211.0 (C), 175.4 (C), 144.0 (C), 133.6 (C),
129.8 (2 ¥ CH), 127.3 (2 ¥ CH), 122.8 (CH), 56.8 (CH), 55.5 (CH),
49.8 (CH2), 42.5 (CH), 21.5 (CH3), 21.4 (CH3), 12.8 (CH3).
SMe
SMe
HRMS: m/z calcd for C16H19NO3S (M+) 305.1079. Found: 305.1086
3-Methyl-3-(3-methylthio-2-propynloxy)-1-propene (10a)
The title compound was prepared from 220 mg (2.0 mmol) of enyne
9a as described for the preparation of 16a to afford 96 mg (31%) of
10a as a slightly yellow oil; Rf = 0.41 (5% EtOAc/Hexanes).
IR (thin film): n = 3078, 2180, 1642, 1081 cm-1.
1H NMR (CDCl3): d = 5.65 (ddd, J = 17.7, 10.2, 7.7 Hz, 1H), 5.23-
5.12 (m, 2H), 4.22 (d, 1H), 4.08 (d, J = 16.2 Hz, 1H), 4.04-4.16 (m,
1H), 2.35 (s, 3H), 1.23 (d, J = 6.3 Hz, 3H).
13C NMR (CDCl3): d = 139.2 (CH), 117.0 (CH2), 89.5 (C), 77.7 (C),
75.6 (CH), 56.1 (CH2), 21.1 (CH3), 19.0 (CH3).
HRMS: m/z calcd for C8H13OS (M+H)+) 157.0687. Found:
157.0691.
N-2-(cis-Pent-3-enyl)-N-(3-methylthioprop-2-ynyl)-4-methyl-
benzenesulfonamide (8a)
BuLi (312 mL, 0.81 mmol, 2.58 M in hexanes, 1.15 equiv) was add-
ed to a solution of N-2-(cis-pent-3-enyl)-N-2-propynyl-4-methyl-
benzenesulfonamide (194 mg, 0.70 mmol) in THF (3 mL) at
-78 °C. After 45 min at -78 °C, methyl thiocyanate (62 mL, 0.91
mmol, 1.3 equiv) was added dropwise to the orange solution. The
color faded instantly to yellow, the turbid solution was stirred at
-78 °C for 1 h and then allowed to warm to -20 °C. Sat. NH4Cl (3
mL) was added and the solution allowed to attain r.t. The aqueous
layer was extracted with EtOAc (3 ¥ 15 mL), and the combined or-
ganic layers dried (MgSO4), filtered and concentrated to a yellow
oil. Column chromatography on silica (0-3.5% EtOAc in hexanes)
gave the title compound as a pale yellow oil, which solidified on
standing to an off-white solid (190 mg, 84%).
trans-3-Methyl-6-methylthio-3a,4-dihydro-1H,3H-cyclopen-
ta[c]furan-5-one (10bb)
Enyne 10a (65 mg, 0.42 mmol) was cyclized according to general
procedure A to afford 63 mg (81%) of a 11.9:1 diastereomeric mix-
ture of bicyclopentenones 10bb and 10ba as determined by GC
analysis of the crude reaction mixture.
IR (KBr disc): n = 2980, 2928, 2178, 1652, 1595, 1341, 1161 cm-1.
1H NMR (300 MHz, CDCl3): d = 7.77 (d, J = 8.3 Hz, 2H), 7.27 (d,
J = 8.3 Hz, 2H), 5.57-5.40 (m, 2H), 4.84 (approx. pentet, J = 7.1
Hz, 1H), 4.25 (d, J = 18.9 Hz, 1H), 4.17 (d, J = 18.9 Hz, 1H), 2.41
Synthesis 2000, No. 7, 1009–1019 ISSN 0039-7881 © Thieme Stuttgart · New York

1016
B. L. Pagenkopf et al.
PAPER
10bb: Rf = 0.45 (50% EtOAc/hexanes); white crystals, mp 67-
78 °C.
The structural assignment is consistent with the following NOE da-
ta.
IR (thin film): n = 1709, 1629, 1442, 1067 cm-1.
3%
0.3%
1H NMR (CDCl3): d = 4.71 (dd, J = 16.3, 1.5 Hz, 1H), 4.55 (dt,
J = 16.3, 1.43 Hz, 1H), 3.49-3.40 (m, 1H), 2.76-2.68 (m, 1H), 2.64
(dd, J = 6.4, 17.1 Hz, 1H), 2.36 (s, 3H), 2.11 (dd, J = 17.4, 2.9 Hz,
1H), 1.36 (d, J = 6.0 Hz, 3H).
13C NMR (CDCl3): d = 205.1 (C), 176.1 (C), 132.9 (C), 79.9 (CH),
66.6 (CH2), 51.3 (CH), 38.8 (CH2), 19.4 (CH3), 14.6 (CH3).
1%
H3C
H
H3C
H
2.5%
O
H
H
O
O
O
0%
2%
H
H
H
H
S(t-Bu)
S(t-Bu)
HRMS: m/z calcd for C9H12O2S (M+) 184.0558. Found: 184.0556.
cis-3-Methyl-6-methylthio-3a,4-dihydro-1H,3H-cyclopen-
ta[c]furan-5-one (10ba)
cis-6-tert-Butylthio-3-methyl-3a,4-dihydro-1H,3H-cyclopen-
ta[c]furan-5-one (11ba)
Waxy tan-colored semi-solid; Rf = 0.32 (50% EtOAc/hexanes).
1H NMR (CDCl3): d = 4.59 (s with fine structure, 2H), 4.54-4.43
(m, 1H), 3.42-3.34 (m, 1H), 2.63 (dd, J = 18.0, 6.6 Hz), 2.40 (s,
3H), 2.17 (dd, J = 16.7, 3.5 Hz, 1H), 0.94 (d, J = 6.6 Hz, 3H)
1H NMR (CDCl3): d = 4.67 (s with fine structure, 2H), 4.64 (m, 1H),
3.54-3.95 (m, 1H), 2.71 (dd, J = 17.9, 6.7 Hz, 1H), 2.22 (dd,
J = 17.9, 4.0 Hz, 1H) 1.2 (s, 9H), 0.95 (d, J = 6.6 Hz, 3H).
HRMS: m/z calcd for C9H12O2S (M+) 184.0558. Found: 184.0553.
HRMS: m/z calcd for C12H18O2S (M+) 226.1028. Found: 225.1034.
3-Methyl-3-(3-[(1,1-dimethylethyl)thio]-2-propynloxy)prop-1-
ene (11a)
4,4-Dimethyl-1-ethoxyhept-7-en-1-yn-3-ol
To a solution of ethoxy acetylene (0.84 g of a 50% solution in hex-
ane, 6.0 mmol, 1.2 equiv) in THF (10 mL) cooled to -78 °C was
added a solution of n-BuLi (2.37 mL, 2.32 M in heptane, 5.5 mmol,
1.1 equiv) dropwise over 5 min and the reaction mixture was stirred
for an additional 5 min. Next, 2,2-dimethylpent-4-en-1-al (0.56 g,
5.0 mmol, 1.0 equiv) was added, neat. The dry-ice acetone bath was
removed and the reaction mixture was allowed to warm to r.t. while
being vigorously stirred. After stirring for 10 min at 26 °C, the re-
action mixture was treated with sat. NaHCO3 (5 mL) and diluted
with Et2O (15 mL). The organic layer was separated and the aque-
ous layer was extracted with Et2O (2 ¥ 15 mL) and the combined
organic fractions were washed with H2O (5 mL), brine (10 mL) and
concentrated in vacuo. The residue was purified by gradient flash
chromatography on silica gel (2-10% EtOAc/hexane for elution
with approx. 0.1% TEA added) to afford 0.847 g (93%) of the title
compound as a colorless oil.
To a solution of enyne 9a 146 mg (1.3 mmol) and [(Me2)N]3P(O)
(271 mL,1.5 mmol,1.2 equiv) in THF (2 mL) cooled to -78 °C was
added a solution of n-BuLi (0.65 mL, 2.20 M in heptane, 1.4 mmol,
1.1 equiv) dropwise over 2 min. After 5 min, a solution of 4-(t-bu-
tylthio)tosylate (381 mg, 1.5 mmol, 1.2 equiv) in THF (4 mL)
cooled to -78 °C was added via cannula and the resulting solution
was allowed to warm to r.t., and was stirred overnight. After 8 h, the
solution was treated with half-sat. NH4Cl (10 mL) and the aqueous
phase was separated. The aqueous phase was extracted with Et2O
(3 ¥ 15 mL) and the combined organic fractions were washed with
H2O (3 ¥ 5 mL), brine (20 mL), dried (MgSO4), filtered and concen-
trated in vacuo. The residue was purified by silica gel chromatogra-
phy (hexane) and afforded 183 mg (71%) of the title compound as
a slightly yellow oil; Rf = 0.31 (5% EtOAc/hexanes).
IR (thin film): n = 3079, 2175, 1643, 1366, 1083 cm-1.
1H NMR (CDCl3): d = 5.65 (ddd, J = 17.5, 10.2, 7.6 Hz, 1H), 5.21-
5.10 (m, 2H), 4.28 (d, 16.4 Hz, 1H), 4.15 (d, J = 16.4 Hz, 1H),
4.10-3.99 (m, 1H), 1.36 (s, 9H), 1.23 (s, 3H), 1.20 (s, 3H).
13C NMR (CDCl3): d = 139.4 (CH), 117.0 (CH2), 93.9 (C), 75.7 (C),
75.4 (CH), 56.3 (CH2), 47.7 (C), 30.3 (CH3), 21.2 (CH3).
IR (thin film): n = 3440 (br), 3075, 2263, 1640, 1234, 1007, 912
cm-1.
1H NMR (CDCl3): d = 5.89-5.75 (m, 1H), 5.07-4.99 (m, 2H), 4.07
(q, J = 7.1 Hz, 2H), 4.06 (s, 1H), 2.15-2.04 (m, 2H), 1.70 (br s, 1H),
1.35 (t, J = 7.1 Hz, 3H), 0.91 (s, 3H), 0.90 (s, 3H).
13C NMR (CDCl3): d = 135.7 (CH), 117.7 (CH2), 95.0 (C), 74.9
(CH2), 70.6 (CH), 43.3 (CH2), 39.3 (C), 38.2 (C), 23.1 (CH3), 23.0
(CH3), 14.8 (CH3).
HRMS: m/z calcd for C11H18OS (M+) 198.1078. Found: 198.1071.
trans-6-tert-Butylthio-3-methyl-3a,4-dihydro-1H,3H-cyclopen-
ta[c]furan-5-one (11bb)
Enyne 11a (40 mg, 0.20 mmol) was cyclized according to general
procedure A except that gradient flash chromatography was per-
formed with 5-10% EtOAc/hexanes to afford 35 mg (78%) of a
41.6:1 diastereomeric mixture of bicyclopentenones 11bb and 11ba
as determined by GC analysis of the crude reaction mixture.
4,4-Dimethyl-5-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-7-
ethoxyhept-1-en-6-yne (12a)
A solution of t-BuMe2SiCl (178 mg, 1.18 mmol, 1.05 equiv) and
imidazole (191 mg, 2.80 mmol, 2.5 equiv) in DMF (1 mL) was
stirred for 10 min at r.t. and subsequently treated with a solution of
4,4-dimethyl-1-ethoxyhept-7-en-1-yn-3-ol (205 mg, 1.12 mmol) in
DMF (0.25 mL). The resulting solution was stirred for 96 h and then
diluted with hexane/Et2O, 6:1 (20 mL) and sat. K2CO3 (20 mL). The
organic layer was separated and the aqueous layer was washed with
hexane/Et2O, 6:1 (2 ¥ 15 mL). The aqueous layers were combined
and washed with H2O (25 mL portion), brine (25 mL), dried
(MgSO4), filtered and concentrated in vacuo. The residual material
was purified by flash chromatography on silica gel (hexane) to af-
ford 248 mg (76%) of the title compound as a colorless oil.
11bb: Colorless needles; mp 70-71 °C.
IR (thin film): n = 1713, 1633, 1365 cm-1.
1H NMR (CDCl3): d = 4.76 (dd, J = 17.0, 1.0 Hz, 1H), 4.61 (dt,
J = 17.0, 1.2 Hz, 1H), 3.56-3.47 (m, 1H), 2.89-2.82 (m, 1H), 2.73
(dd, J = 17.6, 6.6 Hz, 1H), 2.15 (dd, J = 17.1, 3.6 Hz, 1H), 1.40 (d,
J = 6.0 Hz, 3H), 1.27 (s, 9H).
13C NMR (CDCl3): d = 206.4 (C), 191.2 (C), 129.4 (C), 79.9 (CH),
67.0 (CH2), 50.7 (CH), 48.4 (C), 38.4 (CH2), 31.7 (CH3), 19.2
(CH3).
IR (thin film): n = 3076, 2264, 1640, 1250, 1067, 1005, 837 cm-1.
1H NMR (CDCl3): d = 5.87-5.73 (m, 1H), 5.02-4.97 (m, 2H), 4.05
(q, J = 7.1 Hz, 2H), 4.06 (s, 1H), 2.14-2.01 (m, 2H), 1.35 (t, J = 7.1
HRMS: m/z calcd for C12H18O2S (M+) 226.1028. Found: 225.1021.
Synthesis 2000, No. 7, 1009–1019 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
(Alkylthio)alkynes as Addends in the Co(0) Catalyzed Intramolecular Pauson-Khand Reaction
1017
Hz, 3H), 0.89 (s, 9H), 0.88 (s, 3H), 0.87 (s, 3H), 0.12 (s, 3H), 0.06
(s, 3H).
2-(4-Methyl-2,3-pentadienyl)-2-(2-propynyl)malonic Acid
Dimethyl Ester (13a)
To a suspension of NaH [0.187 g (deoiled), 7.80 mmol, 1.10 equiv]
in DMF/THF (7:3 mL) at 0 °C was added 2-(4-methylpenta-2,3-di-
enyl)malonic acid dimethyl ester (1.50 g, 7.07 mmol, 1.00 equiv)
dropwise. The reaction mixture was allowed to stir at r.t. for 1 h,
then the reaction vessel was cooled to 0 °C and propargyl bromide
(0.70 mL, 8.5 mmol, 1.2 equiv) was added dropwise. The resulting
suspension was allowed to warm to r.t. and was stirred overnight.
The reaction mixture was quenched with the addition of sat. NH4Cl
(5 mL) and then poured into EtOAc/H2O (50:25 mL). The organic
phase was washed with H2O (20 mL), brine (20 mL), and dried
(Na2SO4). Evaporation of solvent and purification by flash chroma-
tography (SiO2, 5% EtOAc in hexanes) afforded 1.65 g (92%) of 2-
(4-methylpenta-2,3-dienyl)-2-(2-propynyl)malonic acid dimethyl
ester (13a) as a slightly yellow oil.
13C NMR (CDCl3): d = 136.1 (CH), 117.2 (CH2), 94.4 (C), 74.5
(CH2), 70.9 (CH), 43.1 (CH2), 39.8 (C), 38.8 (C), 26.2 (CH3), 23.2
(CH3), 23.1 (CH3), 18.6 (C), 14.8 (CH3), -3.7 (CH3), -4.8 (CH3).
HRMS (CI/NH3): m/z calcd for C17H33O2Si (M+H)+ 297.2250.
Found: 297.2244.
trans-5,5-Dimethyl-4-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-3-
[(ethyl)oxy]-4,5,6,6a-tetrahydro-2(1H)-pentalenone (12bb)
Enyne 12a (74 mg, 0.25 mmol) was cyclized according to general
procedure A to afford 68 mg (84%) of a 0.72:1 diastereomeric mix-
ture of bicyclopentenones 12bb and 12ba as determined by GC
analysis of the crude reaction mixture.
12bb: Rf = 0.22 (5% EtOAc/hexane).
IR (thin film): n = 1712, 1663, 1472, 1257, 1127, 838 cm-1.
IR (NaCl, thin film): n = 3292 (br s), 2981 (s), 2954 (s), 2910 (s),
2854 (s), 2123 (m), 1969 (m), 1735 (br s), 1438 (s), 1210 (s br) cm-
1H NMR (CDCl3): d = 4.28 (s, 1H), 4.24-4.13 (m, 2H), 3.17-3.10
(m, 1H), 2.65 (dd, J = 18.2, 6.4 Hz, 1H), 2.02-1.91 (m, 2H), 1.29
(t, J = 7.0 Hz, 3H), 1.08 (s, 3H), 1.03 (dd, J = 12.8, 7.6 Hz, 1H),
0.87 (s, 3H), 0.86 (s, 3H), 0.08 (s, 3H), 0.02 (s, 3H).
13C NMR (CDCl3): d = 205.6 (C), 158.5 (C), 148.0 (C), 76.6 (CH),
66.2 (CH2), 46.5 (C), 44.2 (CH2), 43.2 (CH2), 36.6 (CH), 29.8
(CH3), 26.2 (CH3), 24.3 (CH3), 18.6 (C), 15.9 (CH3), -4.1 (CH3),
-4.5 (CH3).
1
.
1H NMR (300 MHz, CDCl3): d = 4.74 (m, 1H), 3.71 (s, 6H), 2.95
(s, 2H), 2.68 (d, J = 7.6 Hz, 2H), 2.30 (s, 1H), 1.63 (s, 6H).
13C NMR (75.5 MHz, CDCl3): d = 203.7 (C), 169.8 (2 ¥ C), 95.2
(C), 82.0 (CH), 78.5 (C), 71.1 (CH), 56.9 (C), 52.5 (2 ¥ CH3), 32.2
(CH2), 22.2 (CH2), 20.2 (2 ¥ CH3).
HRMS (EI): m/z calcd for C14H18O4 (M+) 250.1205. Found:
250.1203.
HRMS (CI/NH3): m/z calcd for C18H33O3Si (M+1)+ 325.2199.
Found: 324.2192.
1-Isopropylidene-2-oxo-4,5,6,6a-tetrahydro-1H-pentalene-5,5-
dicarboxylic Acid Dimethyl Ester (13b) and 5,5-Dimethyl-2-
oxo-1,2,4,6-tetrahydroindene-5,5-dicarboxylic Acid Dimethyl
Ester (13c)
The indicated stereochemistry is consistent with the following NOE
data.
The title compounds were prepared as a mixture of isomers (5.8:1)
in 47% yield using Procedure A except that 10 mol% Co2(CO)8 was
used (12 h). Purification by flash chromatography (SiO2, 15%
EtOAc in hexanes to 30% EtOAc in hexanes gradient for elution)
afforded 33 mg (47%) of 1-isopropylidene-2-oxo-4,5,6,6a-tetrahy-
dro-1H-pentalene-5,5-dicarboxylic acid dimethyl ester (13b) and
5,5-dimethyl-2-oxo-1,2,4,6-tetrahydroindene-5,5-dicarboxylic acid
dimethyl ester (13c) as a slightly yellow oil. Ester 13b was found
identical in all respects to an authentic sample prepared according
to a literature procedure.19c
H
O
0%
H
OEt
tBuMe2SiO
cis-5,5-Dimethyl-4-[[(1,1-dimethylethyl)dimethylsilyl]oxy]-3-
[(ethyl)oxy]-4,5,6,6a-tetrahydro-2(1H)-pentalenone (12ba)
IR (thin film): n = cm-1.
1H NMR (CDCl3): d = 4.42 (s, 1H), 4.24-4.13 (m, 2H), 2.76-2.68
(m, 1H), 2.56 (dd, J = 17.7, 6.4 Hz, 1H), 1.97 (dd, J = 17.7, 2.8 Hz,
1H), 1.84 (dd, J = 12.9, 9.2 Hz, 1H), 1.24 (t, J = 7.0 Hz, overlapping
with CHH, 4H), 1.10 (s, 3H), 0.91 (s, 9H), 0.90 (s, 3H), 0.12 (s, 3H),
0.09 (s, 3H).
13C NMR (CDCl3): d = 205.6 (C), 163.9 (C), 149.0 (C), 79.7 (CH),
66.3 (CH2), 45.0 (C), 44.7 (CH2), 42.8 (CH2), 33.4 (CH), 29.0
(CH3), 26.3 (CH3), 25.4 (CH3), 18.7 (C), 16.0 (CH3), -4.4 (CH3).
1-Isopropylidene-2-oxo-4,5,6,6a-tetrahydro-1H-pentalene-5,5-
dicarboxylic Acid Dimethyl Ester (13b)
Major isomer; mp 80-81 °C.
IR (NaCl, thin film): n = 2993 (m), 2955 (m), 2848 (m), 1734 (br s),
1690 (s), 1651 (s), 1632 (s), 1435 (s), 1264 (br s) cm-1.
1H NMR (300 MHz, C6D6): d = 5.88 (br s, 1H), 3.36-3.25 (ob-
scured peak, 1H), 3.33 (s, 3H), 3.29 (s, 3H), 3.11 (m, 1H), 2.98 (m,
1H), 2.90 (dd, J = 12.6, 7.8 Hz, 1H), 2.27 (s, 3H), 1.53 (approx. t,
J = 12.6 Hz, 1H), 1.46 (s, 3H).
13C NMR (75.5 MHz, C6D6): d = 196.2 (C), 174.2 (C), 172.0 (C),
171.0 (C), 145.1 (C), 133.3 (C), 128.7 (CH), 61.2 (C), 52.66 (CH3),
52.48 (CH3), 48.9 (CH), 38.0 (CH2), 34.4 (CH2), 24.1 (CH3), 19.5
(CH3).
HRMS (CI/NH3): m/z calcd for C18H33O3Si (M+) 324.2199. Found:
324.2195.
The indicated stereochemistry is consistent with the following NOE
data.
HRMS (EI): m/z calculated for C15H18O5 (M+) 278.1156. Found:
278.1154.
5,5-Dimethyl-2-oxo-1,2,4,6-tetrahydroindene-5,5-dicarboxylic
Acid Dimethyl Ester (13c)
O
5%
HRMS (EI): m/z calcd for C15H20O5 (M+) 280.1166. Found:
280.1154.
tBuMe2SiO
H
OEt
Synthesis 2000, No. 7, 1009–1019 ISSN 0039-7881 © Thieme Stuttgart · New York

1018
B. L. Pagenkopf et al.
PAPER
5-Methylene-4-(propen-2-yl)-cyclohex-3-ene-1,1-dicarboxylic
Acid Dimethyl Ester (13d)
13C NMR (75.5 MHz, CDCl3): d = 193.3 (C), 172.0 (C), 171.1 (C),
168.6 (C), 147.7 (C), 135.0 (C), 131.5 (C), 61.1 (C), 53.3 (CH3),
53.1 (CH3), 47.9 (CH), 37.7 (CH2), 34.3 (CH2), 24.6 (CH3), 19.9
(CH3), 14.6 (CH3).
HRMS (EI): m/z calcd for C16H20O5S (M+) 324.1026. Found:
324.1031.
The title compound was isolated from a Co2(CO)8-catalyzed carbo-
nylative cyclization reaction of 2-(4-methylpenta-2,3-dienyl)-2-(2-
propynyl)malonic acid dimethyl ester (13a) using Procedure A. Pu-
rification by flash chromatography (SiO2, 15% EtOAc in hexanes to
30% EtOAc in hexanes gradient for elution) afforded crude triene
13d. Further purification by flash chromatography (neutral Al2O3,
5% EtOAc in hexanes to 15% EtOAc in hexanes gradient for elu-
tion) afforded 13 mg (21%) of the title compound as a colorless oil.
N-(But-3-ynyl)-N-(4-methylpenta-2,3-dienyl)-4-methylbenz-
enesulfonamide (15a)
To solution of N-(but-3-ynyl)-4-methylbenzenesulfonamide (1.72
g, 6.74 mmol, 1.00 equiv), Ph3P (2.73 g, 10.4 mmol, 1.35 equiv) and
4-methylpenta-2,3-dien-1-ol (0.985 g, 10.0 mmol, 1.30 equiv) in
THF (23 mL) at 0 °C was added diisopropylazodicarboxylate (2.05
mL, 10.4 mmol, 1.35 equiv) over 10 min. The resulting solution was
allowed to slowly warm to r.t. and stirred overnight (12 h). Evapo-
ration of solvent and purification by flash chromatography (SiO2,
hexanes to 5% EtOAc in hexanes gradient for elution) afforded 2.05
g (91%) of N-(but-3-ynyl)-N-(4-methylpenta-2,3-dienyl)-4-methyl-
benzenesulfonamide (15a) as a colorless solid. Recrystallization
from EtOAc/hexanes afforded colorless prisms; mp 67-68 °C.
IR (NaCl, thin film): n = 3091 (w), 2955 (m), 2918 (m), 2849 (m),
1735 (s) 1436 (m) cm-1.
1H NMR (300 MHz, CDCl3): d = 5.59 (dt, J = 4.1, 1.0 Hz, 1H),
4.99-4.93 (m, 3H), 4.81 (m, 1H), 3.69 (s, 6H), 2.86 (s, 2H), 2.70 (d,
J = 4.1 Hz, 2H), 1.82 (d, J = 1.0 Hz, 3H).
13C NMR (75.5 MHz, CDCl3): d = 171.3 (2 ¥ C), 144.1 (C), 141.7
(C), 137.8 (C), 123.0 (CH), 114.5 (CH2), 114.0 (CH2), 54.3 (2 ¥ C),
52.7 (CH3), 37.4 (CH2), 31.5 (CH2), 22.9 (CH3).
HRMS (EI): m/z calcd for C14H18O4 (M+) 250.1205. Found:
250.1202.
IR (NaCl, thin film): n = 3292 (br m), 2980 (m), 2912 (m), 2869 (m),
2120 (w), 1968 (w), 1598 (m), 1344 (br s) cm-1.
2-(4-Methyl-2,3-pentadienyl)-2-(3-methylthio-2-propynyl)mal-
onic Acid Dimethyl Ester (14a)
1H NMR (300 MHz, CDCl3): d = 7.64 (d, J = 8.2 Hz, 2H), 7.24 (d,
J = 8.2 Hz, 2H), 4.70 (m, 1H), 3.73 (d, J = 7.1 Hz, 2H), 3.28 (ap-
prox. t, J = 7.6 Hz, 2H), 2.42 (dt, J = 7.6, 2.5 Hz, 2H), 2.36 (s, 3H),
1.93 (t, J = 2.5 Hz, 1H), 1.61 (s, 3H), 1.60 (s, 3H).
13C NMR (75.5 MHz, CDCl3): d = 203.4 (C), 143.2 (C), 136.7 (C),
129.6 (2 ¥ CH), 126.9 (2 ¥ CH), 96.9 (C), 84.1 (CH), 80.7 (C), 70.0
(CH), 48.2 (CH2), 45.5 (CH2), 21.3 (CH3), 20.1 (2 ¥ CH3), 18.9
(CH2).
To a suspension of NaH (98 mg (60% dispersion in oil), 2.44 mol,
1.08 equiv) in DMF/THF (2:1 mL) at 0 °C was added 2-(4-methyl-
penta-2,3-dienyl) malonic acid dimethyl ester (13a) (0.479 g, 2.26
mmol, 1.00 equiv). The resulting mixture was allowed to stir for 30
min at which time 1-chloro-3-thiomethylpropyne (341 mg, 2.83
mmol, 1.25 equiv) was added dropwise. The resulting solution was
stirred for 4 h at r.t., and then quenched with the addition of sat.
NH4Cl (1 mL). The suspension was partitioned between Et2O/H2O
(25:10 mL). The organic phase was washed with H2O (10 mL) and
dried (MgSO4). Evaporation of solvent and purification by flash
chromatography (SiO2, hexanes to 5% EtOAc in hexanes gradient
for elution) afforded 400 mg (60%) of 2-(4-methylpenta-2,3-die-
nyl)-2-(3-methylthio-2-propynyl)malonic acid dimethyl ester (14a)
as a yellow oil.
HRMS (EI): m/z calcd for C17H21NO2S (M+) 303.1292. Found:
303.1293.
2-[(4-Methylbenzene)sulfonyl]-5-isopropylidene-1,2,3,4,4a,5-
hexahydro-[2]-pyridin-6-one (15b)
The title compound was prepared in 30% yield using Procedure A
except that 10 mol% Co2(CO)8 was used.
IR (NaCl, thin film): n = 2980 (m), 2952 (s), 2930 (s), 2853 (m),
IR (thin film, NaCl): n = 2922 (m), 2850 (m), 1688 (s), 1645 (m),
2194 (w), 1696 (m), 1234 (br s), 1436 (s), 1288 (s), 1208 (br s) cm-1.
1627 (s), 1361 (m), 1340 (m), 1163 (s), 1097 (m), 720 (m) cm-1.
1H NMR (300 MHz, CDCl3): d = 4.72 (m, 1H), 3.69 (s, 6H), 2.93
(s, 2H), 2.66 (d, J = 7.5 Hz, 2H), 2.28 (s, 3H), 1.62 (s, 3H), 1.61 (s,
3H).
13C NMR (75.5 MHz, CDCl3): d = 203.9 (C), 170.2 (2 ¥ C), 95.3
(C), 87.4 (C), 82.3 (CH), 73.7 (C), 57.4 (C), 52.6 (2 ¥ CH3), 32.6
(CH2), 24.1 (CH2), 20.4 (2 ¥ CH3), 19.2 (CH3).
1H NMR (300 MHz, CDCl3): d = 7.62 (d, J = 8.2 Hz, 2H), 7.29 (d,
J = 8.2 Hz, 2H), 5.96 (s, 1H), 4.36 (ddd, J = 7.5, 5.6, 1.8 Hz, 1H),
4.10 (m, 1H), 3.36 (dd, J = 10.8, 5.6 Hz, 1H), 2.72-2.57 (m, 2H),
2.40 (s, 3H), 2.40-2.27 (m, 2H), 2.25 (s, 3H), 1.96 (s, 3H).
13C NMR (75.5 MHz, CDCl3): d = 195.4 (C), 168.4 (C), 148.7 (C),
143.9 (C), 134.1 (C), 130.8 (CH), 129.9 (2 ¥ CH), 129.7 (C), 127.3
(2 ¥ CH), 51.7 (CH2), 46.8 (CH2), 44.8 (CH), 29.89 (CH2), 24.2
(CH3), 21.5 (CH3), 20.1 (CH3).
HRMS (EI): m/z calcd for C15H20O4S (M+) 296.1076. Found:
296.1082.
HRMS (EI): m/z calcd for C18H21NO3S (M+) 331.1798. Found:
331.1804.
1-Isopropylidene-2-oxo-4,5,6,6a-tetrahydro-3-methylthio-1H-
pentalene-5,5-dicarboxylic Acid Dimethyl Ester (14b)
The title compound was prepared in 84% yield using Procedure A.
Purification by flash chromatography (SiO2, 15% EtOAc in hexanes
to 30% EtOAc in hexanes gradient for elution) afforded 69 mg
(84%) of 1-isopropylidene-2-oxo-4,5,6,6a-tetrahydro-3-methyl-
thio-1H-pentalene-5,5-dicarboxylic acid dimethyl ester (14b); mp
90-91 °C.
N-(4-Methylthiobut-3-ynyl)-N-(4-methylpenta-2,3-dienyl)-4-
methylbenzenesulfonamide (16a)
To a solution of N-(but-3-ynyl)-N-(4-methylpenta-2,3-dienyl)-4-
methylbenzenesulfonamide (15a) (1.57 g, 4.69 mmol, 1.00 equiv)
in THF (16 mL) at -78 °C was added n-BuLi (3.4 mL of a 1.6 M
solution in hexanes, 5.4 mmol, 1.2 equiv) dropwise. After stirring
15 min at -78 °C, MeSCN (0.40 mL, 5.9 mmol, 1.3 equiv) was add-
ed dropwise. The solution was stirred 30 min at -78 °C, and then
placed in a 0 °C bath for 15 min, at which time H2O (5 mL) was add-
ed. The mixture was partitioned between EtOAc/H2O (50:50 mL),
washed with H2O (2 ¥ 25 mL), brine (50 mL) and dried (Na2SO4).
Evaporation of solvent and purification by flash chromatography
IR (NaCl, thin film): n = 2995 (m), 2954 (m), 1733 (s), 1682 (s),
1651 (m), 1622 (m), 1435 (br m), 1260 (br m), 1063 (m) cm-1.
1H NMR (300 MHz, CDCl3): d = 3.80 (s, 3H), 3.73 (s, 3H), 3.51 (dd
with fine structure, J = 12.5, 7.3 Hz, 1H), 3.33 (d, J = 19.4 Hz, 1H),
3.26 (d, J = 19.4 Hz, 1H), 2.91 (dd, J = 12.5, 7.3 Hz, 1H), 2.42 (s,
3H), 2.27 (s, 3H), 1.91 (s, 3H), 1.67 (approx. t, J = 12.5 Hz, 1H).
Synthesis 2000, No. 7, 1009–1019 ISSN 0039-7881 © Thieme Stuttgart · New York

PAPER
(Alkylthio)alkynes as Addends in the Co(0) Catalyzed Intramolecular Pauson-Khand Reaction
1019
(SiO2, 5 ¥ 2 cm, 5% EtOAc in hexanes) afforded 2.05 g (91%) of
the title compound as an orange-yellow oil.
(6) Pagenkopf, B. L.; Livinghouse, T. J. Am. Chem. Soc. 1996,
118, 2285.
(7) (a) Belanger, D. B.; O’Mahony, D. J. R.; Livinghouse, T.
Tetrahedron Lett. 1998, 39, 7636.
(b) Belanger, D. B.; Livinghouse, T. Tetrahedron Lett. 1998,
39, 7641.
(8) Hicks, F. A.; Kablaoui, N. M.; Buchwald, S. L. J. Am. Chem.
Soc. 1999, 121, 5881.
IR (NaCl, thin film): n = 2979 (w), 2927 (m), 1967 (w), 1598 (w),
1344 (m), 1160 (s) cm-1.
1H NMR (300 MHz, CDCl3): d = 7.64 (d, J = 8.2 Hz, 2H), 7.24 (d,
J = 8.2 Hz, 2H), 4.70 (m, 1H), 3.72 (d, J = 7.1 Hz, 2H), 3.26 (ap-
prox. t with fine structure, J = 7.6 Hz, 2H), 2.52 (approx. t with fine
structure, J = 7.6 Hz, 2H), 2.36 (s, 3H), 2.25 (s, 3H), 1.60 (s, 3H),
1.59 (s, 3H).
(9) (a) Kondo, T.; Suzuki, N.; Okada, T.; Mitsudo, T. J. Am.
Chem. Soc. 1997, 119, 6187.
13C NMR (75.5 MHz, CDCl3): d = 203.4 (C), 143.1 (C), 136.8 (C),
129.6 (2 ¥ CH), 126.9 (2 ¥ CH), 96.9 (C), 89.3 (C), 84.1 (CH), 72.2
(C), 48.2 (CH2), 45.6 (CH2), 21.3 (CH3), 20.5 (CH2), 20.1
(2 ¥ CH3), 18.9 (CH3).
HRMS (EI): m/z calcd for C18H23NO2S2 (M+) 349.1167. Found:
349.1170.
(b) Morimoto, T.; Chatani, N.; Fukumoto, Y.; Murai, S. J.
Org. Chem. 1997, 62, 3762.
(10) (a) Jeong, N.; Lee, S.; Sung, B. K. Organometallics 1998, 17,
3642.
(b) Koga, Y.; Kobayashi, T.; Narasaka, K. Chem. Lett. 1998,
249.
(11) Magnus, P; Principe, L. M.; Slater, M. J. J. Org. Chem. 1987,
52, 1483.
(12) Van Wagenen, B. C.; Livinghouse, T. Tetrahedron Lett. 1989,
30, 3495.
(13) For PK reactions with sulfur tethered alkynes, see: Krafft, M.
E.; Scott, I. L.; Romero, R. H.; Feibelmann, S.; Vanpelt, C. E.
J. Am. Chem. Soc. 1993, 114, 7199.
2-[(4-Methylbenzene)sulfonyl]-5-isopropylidene-7-methylthio-
1,2,3,4,4a,5-hexahydro-[2]-pyridin-6-one (16b)
The title compound was prepared in 70% yield using Procedure A.
IR (NaCl, thin film): n = 2925 (w), 1685 (m), 1643 (m), 1607 (m),
1336 (m), 1165 (s), 1098 (m), 749 (m), 651 (m) cm-1.
(14) For a recent utilization of enantio-enriched vinyl sulfoxides in
the stoichiometric PKR, see: Adrio, J.; Carreyero, C. J. Am.
Chem. Soc. 1999, 121, 7411.
(15) Krafft, M. E.; Wilson, A. M.; Dasse, O. A.; Shao, B.; Cheung,
Y. Y.; Fu, Z.; Bonaga, L. V. R.; Mollman, M. K. J. Am. Chem.
Soc. 1996, 118, 6080.
(16) The use of trifluoroethanol (TFE) as a solvent or primary co-
solvent often results in substantial improvements in the
efficiency of carbonylative annulation for representative
Co(0) catalyzed Pauson-Khand reactions. Details concerning
the TFE solvent effect will be published separately.
(17) The (t-butylthio)alkynes or (methylthio)alkynes are
conveniently prepared by deprotonation with n-BuLi, or LDA
[THF, -78 °C] followed by electrophilic trapping with t-
butylthiocyanate, or S-(t-butyl)thiotosylate, or
methylthiocyanate.
1H NMR (300 MHz, C6D6): d = 7.58 (d, J = 8.1 Hz, 2H), 6.78 (d,
J = 8.1 Hz, 2H), 4.38 (ddd, J = 11.2, 5.5, 1.8 Hz, 1H), 3.89 (m, 1H),
2.96 (dd with fine structure, J = 11.2, 5.5 Hz, 1H), 2.77 (m, 1H),
2.28 (s, 3H), 2.19 (s, 3H), 2.16 (m, 1H), 1.90 (s, 3H), 1.84 (m, 1H),
1.61 (approx. t, J = 11.2 Hz, 1H), 1.48 (s, 3H).
13C NMR (75.5 MHz, CDCl3): d = 191.9 (C), 165.4 (C), 149.7 (C),
143.8 (C), 135.8 (C), 133.9 (C), 129.8 (2 ¥ CH), 128.2 (C), 127.2
(2 ¥ CH), 51.5 (CH2), 46.4 (CH2), 43.9 (CH), 28.3 (CH2), 24.1
(CH3), 21.4 (CH3), 20.2 (CH3), 15.0 (CH3).
HRMS (EI): m/z calcd for C19H23NO3S2 (M+) 377.1123. Found:
377.1119.
Acknowledgement
Generous financial support for this research by a grant from the Na-
tional Science Foundation is gratefully acknowledged. The authors
thank Mr. Todd Meyer for experimental assistance.
(18) Bayon, J. C.; Claver, C.; Masdeu-Bulto, A. M. Coord. Chem.
Rev. 1999, 195, 73.
(19) (a) Ahmar, M.; Locatelli, C.; Colombier, D.; Cazes, B.
Tetrahedron Lett. 1997, 38, 5281.
(b) Brummond, K. M.; Wan, H. H.; Kent, J. L. J. Org. Chem.
1998, 63, 6435.
References
(c) Kent, J. L.; Wan, H. H.; Brummond, K. M. Tetrahedron
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(21) Kataoka, T.; Yoshimatsu, M.; Noda, Y.; Sato, T.; Shimizu, H.;
Hori, M. J. Chem. Soc., Perkin Trans. 1 1993, 1, 121.
(1) Current Address: Department of Chemistry and Biochemistry,
Montana State University, Bozeman, MT 59717, USA.
(2) Current Address:Department of Chemistry and Biochemistry,
University of Texas at Austin, Austin, TX 78712, USA.
(3) Current Address: Alcon Laboratories, Fort Worth, TX, USA.
(4) Current Address: Systems Integration Drug Discovery
Company, 9040 S. Rita Rd, #2338, Tucson, AZ 85747, USA.
(5) (a) Geis, O.; Schmalz, H. G. Angew. Chem., Int. Ed. 1998, 37,
911.
Article Identifier:
1437-210X,E;2000,0,07,1009,1019,ftx,en;C01500SS.pdf
(b) Shore, N. E. In Comprehensive Organometallic Chemistry
II, Vol. 12; Hegedus, L. S., Ed.; Elsevier: Oxford, 1995, p 703.
Synthesis 2000, No. 7, 1009–1019 ISSN 0039-7881 © Thieme Stuttgart · New York