PuPHOS and CamPHOS ligands in the intermolecular catalytic pauson-khand reaction

Article abstract of DOI:10.1002/adsc.200700145

The first asymmetric intermolecular cobalt-catalyzed Pauson-Khand reaction is described. The use of the hemilabile CamPHOS ligand provides good conversions and selectivity up to 28 % ee. The catalytic process was studied by in situ FT-IR and it was found that both bridged and non-bridged complexes were present in the reaction mixture. Ourresults suggest that recognition between the alkyne substrate and the ligand is essential to attain stereo-control in the catalytic cyclization.

Full text of DOI:10.1002/adsc.200700145

FULL PAPERS
DOI: 10.1002/adsc.200700145
PuPHOS and CamPHOS Ligands in the Intermolecular Catalytic
Pauson–Khand Reaction
Agustí Lledó,a Jordi Solà,a Xavier Verdaguer,a,* Antoni Riera,a,*
and Miguel A. Maestrob
a
Unitat de Recerca en Síntesi Asim›trica (URSA-PCB), Institute for Research in Biomedicine (IRB Barcelona) and
Departament de Química Orgànica, Universitat de Barcelona, c/Josep Samitier 1–5, 08028 Barcelona, Spain
Fax : (+34)-9-3403-7095; e-mail: xverdaguer@pcb.ub.cat
Departamento de Química Fundamental, Universidade da CoruÇa, 15071 A CoruÇa, Spain
b
Received: March 21, 2007; Published online: September 11, 2007
Supporting information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: The first asymmetric intermolecular results suggest that recognition between the alkyne
cobalt-catalyzed Pauson–Khand reaction is de- substrate and the ligand is essential to attain stereo-
scribed. The use of the hemilabile CamPHOS ligand control in the catalytic cyclization.
provides good conversions and selectivity up to 28%
ee. The catalytic process was studied by in situ FT-IR
and it was found that both bridged and non-bridged Keywords: asymmetric catalysis; cobalt; hydrogen
complexes were present in the reaction mixture. Our bonds; P,S ligands; Pauson–Khand reaction
À
Introduction
a result of the presence of a non-classical C H···O
stabilizing interaction with the strongly polarized CH-
The use of chiral bidentate (P,S) PuPHOS and Cam- OPS methine group of the ligand.[4–6] In both cases,
PHOS ligands in the stoichiometric asymmetric when each of these isolated diastereomeric complexes
Pauson–Khand reaction (PKR) has been extensively reacts with norbornadiene it affords the correspond-
explored by our group.[1–3] Coordination of these li- ing Pauson–Khand cycloadducts in high ee
gands to a terminal alkyne dicobalt complex affords (Scheme 1). This process has been successfully ap-
two diastereomeric bridged complexes in variable plied to the enantioselective synthesis of deoxyphyto-
ratios. While the use of non-functionalized terminal prostanes.[7]
alkynes results in modest diastereoselectivities (up to
A step further in this research would be to make
50% de), the use of a hydrogen bond acceptor (a sul- this process catalytic both in metal and ligand. A
fonyl or an amide moiety) on the alkyne moiety leads number of intramolecular catalytic asymmetric PKRs
to a significant increase in coordination selectivity as or Pauson–Khand-type reactions have been de-
scribed.[8–14] In contrast, a reliable methodology for
the catalytic asymmetric intermolecular PKR has yet
to be reported.[15] This fact encouraged us to explore
the use of our ligands in the catalytic reaction with
norbornadiene. Thus, here we report on the use of
PuPHOS- and CamPHOS-type ligands in the inter-
molecular cobalt-catalyzed Pauson–Khand reaction.
Results and Discussion
Preparation of Ligands
PuPHOS and CamPHOS ligands are prepared from
Scheme 1. Bidentate P,S ligands in the asymmetric PKR.
pulegone and camphorsulfonic acid.[2,3] To further ex-
Adv. Synth. Catal. 2007, 349, 2121 – 2128
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2121

Agustí Lledó et al.
FULL PAPERS
Scheme 2. Synthesis of camphor-derived ligands.
plore the whole potential of the camphor skeleton, are the result of a thermodynamic equilibrium.[4] Ini-
new ligands derived from camphorsulfonic acid were tial selectivity improved on heating over time to
prepared. Reduction of camphorsulfonic acid chloride reach a final diastereomeric ratio.
and reaction with formaldehyde provides two epimer-
Reaction with trimethylsilylacetylene dicobalt hexa-
ic oxathianes (Scheme 2). The major isomer 1a can be carbonyl complex afforded mixtures with low to
purified by crystallization. In contrast, the minor com- modest diastereomeric ratios, as ascertained by
ponent 1b was obtained in pure form by chromatogra- 1H NMR analysis of the final reaction mixtures
phy of the corresponding mother liquors. From oxa- (Table 1, entries 1–8). Only in the case of MeCam-
thianes 1a and 1b, metallation and substitution with PHOS was a good selectivity observed (Table 1,
the appropriate chlorophosphine provided ligands entry 3). In sharp contrast, a high diastereoselectivity
2a–e (Scheme 2). The new phosphine ligands were was observed when an amide was present in the
protected in situ as their borane complexes to prevent alkyne moiety (Table 1, entries 9–17). This result is
À
oxidation of the phosphorus atom, thereby providing due to the stabilizing effect of the intramolecular C
protected ligands 3a, 3b, 3d and 3e in good overall H···O contact. In these cases, diastereomeric ratios up
yield. TolCamPHOS (2c) could not be protected with to 200:1 were obtained with CamPHOS and TolCam-
BH3·SMe2 and was isolated as a free phosphine in PHOS (Table 1, entries 11, 15 and 17). Unusually low
good yield. The greater steric hindrance around the selectivities were attained with CyCamPHOS and t-
phosphorus atom caused by the ortho-tolyl groups BuCamPHOS ligands with diethylpropynamide
may explain why the protection step failed. In this (Table 1, entries 12 and 13). This behavior could be
case, this is not an inconvenience since; even in solu- attributed to the electron-releasing nature of these
tion, the resulting phosphine 2c is resistant to oxida- phosphines, which may reduce the hydrogen bond
tion.
donor capacity of the ligand while at the same time
hamper the isomerization of the bridged complexes.
Suitable crystals for X-ray analysis for the major
and minor isomers of the complex with diethylpropy-
namide and CyCamPHOS (15a and 15b) were ob-
Preparation of Bridged Dicobalt Complexes
To obtain defined catalysts for the PKR, the corre- tained. For the major complex 15a the corresponding
sponding bridged alkyne complexes were prepared. ORTEP plot show the close proximity (2.41 Š) of the
The new ligands 2a–e obtained were subjected to ex- methine proton to the carbonyl oxygen atom (O1),
change reactions with several alkyne dicobalt com- thus providing the stabilizing hydrogen bond
plexes; the results are shown in Table 1 along with (Figure 1). The structure of the minor isomer 15b
data for previously reported ligands. Ligand exchange shows how the hydrogen-bond donor and acceptor
was carried out by heating (658C) a toluene mixture are on opposite sides of the molecule and thus the
À
of the borane-protected ligand and the corresponding stabilizing C H···O=C cannot be realized. In this
hexacarbonyldicobalt complex in the presence of case, the ligand and the alkyne substituent (amide)
DABCO as a borane-deprotecting agent. The diaste- adopt an anti conformation to minimize steric repul-
reomeric ratios observed for the bridged complexes sions.[16]
2122
asc.wiley-vch.de
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 2121 – 2128

PuPHOS and CamPHOS Ligands in the Intermolecular Catalytic Pauson–Khand Reaction
FULL PAPERS
Table 1. Ligand exchange reaction with various alkyne precursors.
Entry
R
Ligand
Complex (yield)
dr[a]
de
Ref.
[1,3]
this study
[2]
this study
this study
this study
this study
this study
[6]
[6]
[6]
[6]
this study
[6]
1
2
3
4
5
6
7
8
TMS
PuPHOS
CamPHOS
4a/4b (91%)
5a/5b (90%)
6a/6b (64%)
7a/7b (84%)
8a/8b (84%)
9a/9b (93%)
10a/10b (86%)
11a/11b (44%)
12a/12b (68%)
13a/13b (74%)
14a/14b (74%)
15a/15b (66%)
16a/16b (78%)
17a/17b (70%)
18a/18b (74%)
19a/19b (74%)
20a/20b (73%)
3:1
5:1
12:1
1.5:1
1.3:1
1:1
50%
66%
85%
20%
13%
0%
33%
55%
94%
90%
99%
51%
51%
90%
96%
76%
99%
ACHTREUNG
MeCamPHOS
CyCamPHOS
t-BuCamPHOS
TolCamPHOS
epiCamPHOS
epiCyCamPHOS
PuPHOS
2:1
3.4:1
32:1
19:1
200:1[b]
3.1:1
3.1:1
19:1
4.3:1
7.3:1
200:1[b]
9
CONEt2
10
11
12
13
14
15
16
17
CamPHOS
TolCamPHOS
CyCamPHOS
t-BuCamPHOS
PuPHOS
CamPHOS
PuPHOS
CON
CON
ACHTREUNG
[6]
[6]
[6]
A
CamPHOS
[a]
1
Diastereomeric ratio was determined by H NMR analysis.
Formation of minor isomer was not detected by TLC analysis.
[b]
Figure 1. ORTEP plot of 15a (left, major diastereomer) and 15b (right, minor diastereomer) showing 50% probability ellip-
soids. Only the hydrogen that can participate in the stabilizing contact is shown.
Catalytic PKRs
ant Teflon screw cap. A 5% molar ratio of the corre-
sponding bridged complex as a catalyst and a 1-fold
With all these complexes in hand we examined the excess of norbornadiene over the alkyne were used.
catalytic PKRs with several alkynes: trimethylsilylace- Soon it became clear that using a single diastereo-
tylene and 2-methyl-3-butyn-2-ol are commercially meric complex or a mixture of them as catalyst had a
available. Diethylpropynamide and diisopropylpropyn- negligible effect on the outcome of the reaction, since
amide were prepared from commercial propynoic equilibration between them occurred readily under
acid following reported procedures.[17] Reactions were the reaction conditions employed. This phenomenon
carried out under carbon monoxide pressure in could be clearly observed by TLC monitoring of the
Schlenk glass tubes, each fitted with a pressure-resist- reaction of TMSC2H with the PuPHOS ligand
Adv. Synth. Catal. 2007, 349, 2121 – 2128
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2123

Agustí Lledó et al.
FULL PAPERS
Table 2. Catalytic PKRs using PuPHOS and CamPHOS ligands.
Entry R1
Catalyst
Ligand
Conditions
Time Product Yield[a] ee[b]
1
2
3
4
5
6
7
8
TMS
TMS
“
“
“
“
4a (R1 =R2)
5a/5b
PuPHOS
CamPHOS
MeCamPHOS
CyCamPHOS
epiCamPHOS
epiCyCamPHOS 2 bar CO/toluene/908C
CamPHOS
CamPHOS
CamPHOS
CyCamPHOS
1 bar CO/toluene/908C
2 bar CO/toluene/708C
1 bar CO/toluene/908C
2 bar CO/toluene/908C
2 bar CO/toluene/908C
20 h
20 h
18 h
3 d
16 h
16 h
(+)-21
(+)-21
(+)-21
(+)-21
(+)-21
(À)-21
(+)-22
(+)-22
(+)-23
(+)-23
(+)-23
(+)-23
(+)-23
(+)-23
(+)-23
(+)-23
(+)-23
(+)-23
(+)-24
70%
98%
60%
10%
22%
6%
12%
90%
91%
34%
25%
20%
80%
20%
90%
91%
45%
30%
40%
3%
0%
5%
15%
4%
5%
40%
16%
23%
8%
1%
0
1%
1%
20%
17%
28%
20%
4%
6a/6b (R1 =R2)
7a/7b (R1 =R2)
10a/10b (R1 =R2)
11a/11b (R1 =R2)
13a (R1 =R2)
13a (R1 =R2)
CONEt2
“
0.5 bar CO/toluene/908C 24 h
2 bar CO/toluene/708C
2 bar CO/toluene/708C
2 bar CO/toluene/708C
2 bar CO/toluene/708C
2 bar CO/toluene/708C
3 bar CO/toluene/708C
2 bar CO/toluene/708C
2 bar CO/toluene/708C
3 bar CO/toluene/708C
CO atm P/toluene/708C
2 bar CO/toluene/558C
2 bar CO/toluene/708C
24 h
24 h
48 h
70 h
48 h
48 h
48 h
24 h
48 h
48 h
48 h
48 h
9
CON(i-Pr)2 18a (R1 =R2)
10
11
12
13
14
15
16
17
18
19
CON
(i-Pr)2 7a/7b (R2 =TMS)
“
“
“
“
“
“
“
“
8a/8b (R2 =TMS) tBuCamPHOS
9a/9b (R2 =TMS)
9a/9b (R2 =TMS)
4a/4b (R2 =TMS)
5a/5b (R2 =TMS)
5a/5b (R2 =TMS)
5a/5b (R2 =TMS)
5a/5b (R2 =TMS)
5a/5b (R2 =TMS)
TolCamPHOS
TolCamPHOS
PuPHOS
CamPHOS
CamPHOS
CamPHOS
CamPHOS
CamPHOS
CMe2OH
[a]
[b]
Flash chromatography isolated yield.
Determined by chiral HPLC analysis.
(Table 2, entry 1). In concordance with the low or tries 9 and 15). A negative effect on the catalytic ac-
modest complexation diastereoselectivity observed tivity was observed when electron-rich phosphines
with trimethylsilylacetylene, very low ees were ob- were used (Table 2, entries 10 and 11). After some ex-
tained when this alkyne was used as substrate for cat- perimentation, we observed that lowering the CO
alytic PKR (Table 2, entries 1–6). Only for CyCam- pressure had a positive effect on the ee (Table 2,
PHOS was a modest excess observed, although at the entry 16) although at the expense of lower yields,
expense of very low conversion (Table 2, entry 4). probably as a result of catalyst decomposition. Lower-
However, when propynamides were used, a significant ing the temperature reaction did not significantly
selectivity was observed with CamPHOS, although affect the selectivity but again had a detrimental
the ees were still modest (Table 2, entries 7–9). A effect on yields, as the reactions slowed down
maximum 40% ee was obtained at 0.5 bar of CO de- (Table 2, entry 18). Finally, when a poorer hydrogen
spite low conversion numbers (Table 2, entry 7), while bond acceptor such as the 2-methyl-3-butyn-2-ol was
16% ee was achieved when the reaction reached com- used the ee obtained was very low (Table 2, entry 19).
pletion (Table 2, entry 8). Slightly higher ees (23%) This observation supports the hypothesis that the
with excellent yield were obtained for the correspond- origin of selectivity is due to the occurrence of the
ing diisopropylamide substrate (Table 2, entry 9).
weak hydrogen-bond when a propynamide substrate
We also carried out the reaction with an alkyne is used.
complex distinct from that used as substrate (Table 2,
entries 10–19). This procedure prevented a contribu-
tion of the initial catalytic cycle to the final ee when a FT-IR Reaction Monitoring
pure diastereomer was used as catalyst. For practical
reasons, the complex with trimethylsilylacetylene To gain further insight into the metallic species in-
(mixture of diastereomers 5a:5b) was used as catalyst; volved in the catalytic process, the reaction between
this did not affect the results (compare Table 2, en- diisopropylpropynamide and norbornadiene catalyzed
2124
asc.wiley-vch.de
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 2121 – 2128

PuPHOS and CamPHOS Ligands in the Intermolecular Catalytic Pauson–Khand Reaction
FULL PAPERS
Scheme 3. Catalytic PKR studied by in situ FT-IR.
by CamPHOS complex 5a/5b was monitored by in-
situ FT-IR spectroscopy (Scheme 3). Infrared spectra
acquired at regular intervals allowed us to follow the
course of the reaction by the appearance of the char-
À
Figure 3. IR absorbance profile of the tetra- and pentacar-
bonyldicobalt species during the catalytic PKR.
acteristic C O stretching band of the enone formed
at around 1698 cmÀ1. Interesting mechanistic informa-
tion was obtained from the region between 1950 and
2100 cmÀ1 where the C O stretching bands of the
À
complex CO ligands appeared. Figure 2 shows this to the initial bridged tetracabonyl complex, rapidly
region at the beginning of the reaction and its evolu- decreased while band B, diagnostic of a pentacarbo-
tion over time. Four characteristic bands were distin- nylic species, grew proportionally. These data show
guished, corresponding to free propynamide (A), the that both tetracarbonyl and pentacarbonyl species are
open pentacarbonylic complex (B) and the initial present in the catalytic reaction mixture. Thus, we
bridged tetracarbonylic complex (C and D). Figure 3 may attribute the decrease in selectivity in the catalyt-
shows the absorbance profiles of cobalt species in the ic process to the presence of the non-bridged com-
reaction mixture. Thus, bands C and D, corresponding plex.
Figure 2. FT-IR stack plot of the metal carbonyl region during the catalytic Pauson–Khand reaction. Visible IR species im-
plied are indicated.
Adv. Synth. Catal. 2007, 349, 2121 – 2128
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2125

Agustí Lledó et al.
FULL PAPERS
Scheme 4. Feasible catalytic cycle for the intermolecular PKR with bridged P,S ligands. Carbonyl ligands are omitted for the
sake of clarity.
As we have previously demonstrated, in the stoi- dicobaltcarbonyl system is an efficient catalyst for the
chiometric reaction, a high stereoselectivity/specificity intermolecular process and provides good conversions
was observed when a diastereomerically pure bridged and yields. The occurrence of an intramolecular hy-
complex reacted with norbornadiene. FT-IR monitor- drogen bond between the ligand and the substrate is
ing of the catalytic process revealed that under CO essential to attain selectivity in the reaction. FT-IR
pressure, equilibrium between the bridged tetracar- monitoring of the reaction mixture revealed that
bonyl complexes I and the open complexes II takes under CO pressure the bridged complex coexists with
place (Scheme 4). While a high diastereomeric bias the open pentacarbonylic species. Thus, reaction
operates for bridged complexes, low selectivity is ex- through the non-bridged complex is thought to be re-
pected in the equilibration of non-bridged complexes sponsible for the low selectivity observed. Further
II. In this situation, PKR through I is expected to tuning of the P,S ligand system should provide en-
occur with elevated selectivity while reaction through hanced stereocontrol in the catalytic intermolecular
II will provide poor stereocontrol. In addition, for the Pauson–Khand reaction.
catalytic process we must take into account the step
in which the alkyne enters the catalytic cycle
(Scheme 4). Alkyne coordination to the dicobalt-
ligand moiety may also occur with a range of selectiv-
ity levels.
ExperimentalSection
Noteworthy, despite the multiple species in equilib-
rium in the reaction mixture, which may lead to oppo-
site enantiomers, significant selectivity was observed
when propynamides were used as substrates. This ob-
servation illustrates how the weak, non-classical hy-
drogen bond interaction operating in this system sig-
GeneralRemarks
Solvents were generally distilled under an N2 atmosphere
just before use. Diethyl ether and THF were distilled over
Na/benzophenone, toluene was distilled over molten Na and
nificantly shifts these equilibriums to the major bridg- dichloromethane was distilled over CaH2. DMF was distilled
over CaH2 at 15 mmHg and was stored under N2 over mo-
lecular sieves. Butyllithium (1.6M or 2.5M in hexanes) and
sec-butyllithium (1.7M in cyclohexane) solutions were pur-
chased from Aldrich and were titrated prior to use with p-
phenylbenzyl alcohol. Flash column chromatography was
generally used for purification of compounds, using SiO2
(35–70 mm) as stationary phase. For purification of cobalt
complexes the stationary phase was washed once with dieth-
yl ether to remove moisture and then with hexane before
use. See the Supporting Information for the full characteri-
ed complex I. The fact that the same enantiomer of
the corresponding enone (+)-23 was obtained for the
catalytic and stoichiometric process supports this hy-
pothesis.[5,6]
Conclusions
Here we have described the first intermolecular asym-
metric cobalt-catalyzed PKR. The bridged P,S ligand- zation and analytical data of new compounds.
2126
asc.wiley-vch.de
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 2121 – 2128

PuPHOS and CamPHOS Ligands in the Intermolecular Catalytic Pauson–Khand Reaction
FULL PAPERS
(+)-(1S,4R,6S,8R)-4-Dicyclohexylphosphino-11,11-di-
methyl-5-oxa-3-thiatricyclo[6.2.1.01,6]undecane Borane Com-
plex, epiCyCamPHOS·BH3 (3e): Prepared according to the
general procedure using 341 mg (1.72 mmol) of oxathiane
1b, 1.6 mL (2.24 mmol) of sec-BuLi 1.4m in cyclohexane,
0.49 mL (2.24 mmol) of chlorodicyclohexylphosphine and
0.23 mL (2.30 mmol) of BH3·SMe2. The crude product was
purified by flash chromatography (SiO2, hexanes/AcOEt,
95:5 to 90:10) and the complex epiCamPHOS·BH3 was ob-
tained as a white solid after recrystallization from hexanes/
AcOEt; yield: 624 mg (1.53 mmol, 89%).
GeneralProcedure for the Preparation of Bidentate
Ligands.
To a solution of the required thioisoborneol oxathiane 1a/1b
(400 mg, 2.0 mmol) in 5 mL of THF at À788C were added
dropwise 1.6 mL (2.2 mmol) of sec-BuLi solution (1.4M in
cyclohexane). The flask was allowed to warm to À208C and
after 20 min a solution of 2.02 mmol of the corresponding
chlorophosphine in 2 mL of THF were added via cannula.
After 2 h the reaction mixture was allowed to warm to 08C
and 0.35 mL (3.7 mmol) of BH3·SMe2 were added. Then the
flask was left to reach room temperature for one hour and
the mixture was diluted with Et2O. The flask was cooled
again to 08C and water was carefully added (gas may evolve
violently). The phases were separated and the aqueous layer
was washed with Et2O. The combined organic extracts were
washed with saturated NaCl solution and dried over MgSO4.
The solvent was removed under reduced pressure and the
resulting crude purified by flash chromatography. Yields are
usually over 70%.
(À)-(1S,4S,6R,8R)-4-Dicyclohexylphosphino-11,11-di-
methyl-5-oxa-3-thiatricyclo[6.2.1.01,6]undecane Borane Com-
plex, CyCamPHOS·BH3 (3a): Prepared according to the
general procedure using 388 mg (1.96 mmol) of oxathiane
1a, 1.46 mL (2.1 mmol) of sec-BuLi 1.4M in cyclohexane,
0.47 mL (2.2 mmol) of chlorodicyclohexylphosphine and
0.24 mL (2.5 mmol) of BH3·SMe2. The crude product was
purified by flash chromatography (SiO2, hexanes/Et2O, 95:5)
and complex CyCamPHOS·BH3 was obtained as a colorless
oil; yield: 649 mg (1.7 mmol, 85%).
(À)-(1S,4S,6R,8R)-4-Di-tert-butylphosphino-11,11-dimeth-
yl-5-oxa-3-thiatricyclo[6.2.1.01,6]undecane Borane Complex,
t-BuCamPHOS·BH3 (3b): Prepared according to the general
procedure using 1.05 g (5.0 mmol) of oxathiane 1a, 5.3 mL
(5.3 mmol) of sec-BuLi 1.0M in cyclohexane, 1.1 mL
(5.5 mmol) of di-tert-butylchlorophosphine and 0.86 mL
(6.6 mmol) of BH3·SMe2. The crude product was purified by
flash chromatography (SiO2, hexanes/Et2O, 95:5) and com-
plex t-BuCamPHOS·BH3 was obtained as white crystals;
yield: 1.50 g (4.2 mmol, 83%).
(À)-(1S,4S,6R,8R)-11,11-Dimethyl-5-oxa-3-thia-4-di-o-tol-
ylphosphinotricyclo[6.2.1.01,6]undecane, TolCamPHOS (2c):
Prepared according to the general procedure using 400 mg
(2.02 mmol) of oxathiane 1a, 2.2 mL (2.2 mmol) of sec-BuLi
1.0M in cyclohexane, 500 mg (2.0 mmol) of di-o-tolylchloro-
phosphine and 0.35 mL (3.7 mmol) of BH3·SMe2. The crude
product was purified by flash chromatography (SiO2, hex-
anes/Et2O, 99:1) and then recrystallized from hot AcOEt
under N2; the free ligand TolCamPHOS was obtained as
white crystals; yield: 640 mg (1.6 mmol, 77%).
GeneralProcedure for the Preparation of Cobatl
Complexes
Into a Schlenk tube were weighed 0.24 mmol of the desired
starting alkyne-dicobalt hexacarbonyl complex, 0.24 mmol
of the required ligand-borane complex (L-BH3) and
0.36 mmol of DABCO (1,4-diazabicyclo[2.2.2]octane). The
G
tube was purged with argon and 3 mL of toluene were
added, then the mixture was heated to 658C for the ade-
quate time while CO was periodically removed by means of
vacuum and argon refilling. The solvent was removed under
reduced pressure and the resulting crude is purified by flash
column chromatography.
Co2(m-Et2NCOC2H)(CO)4(m-C19H35OPS) (16a) and (16b):
Prepared according to the general procedure using 100 mg
(0.24 mmol) of dicobalt complex Co2(m-Et2NCOC2H)(CO)6,
85 mg (0.24 mmol) of the complex t-BuCamPHOS·BH3 3g,
40 mg (0.36 mmol) of DABCO and 3 mL of toluene, reac-
tion time 9 h. After chromatographic purification (SiO2,
hexane/AcOEt 90:10 to 60:40) 100 mg (0.14 mmol, 60%) of
the major complex 16a and 30 mg (0.04 mmol, 18%) of the
minor complex 16b were obtained.
Co2(m-TMS-C2H)(CO)4(m-C23H39OPS) (7a) and (7b): Pre-
pared according to the general procedure using 100 mg
(0.26 mmol) of dicobalt complex Co2(m-TMS-C2H)(CO)6,
100 mg (0.24 mmol) of the complex CyCamPHOS·BH3 3e,
40 mg (0.36 mmol) of DABCO and 4 mL of toluene, reac-
tion time 16 h. After chromatographic purification (SiO2,
hexane/AcOEt 95:5) 100 mg (0.20 mmol, 84%) of a 1.5:1
mixture of diastereomeric complexes 7a/7b was obtained.
Co2(m-TMS-COC2H)(CO)4(m-C19H35OPS) (8a) and (8b):
Prepared according to the general procedure using 150 mg
(0.39 mmol) of dicobalt complex Co2(m-TMS-C2H)(CO)6,
142 mg (0.39 mmol) of the complex t-BuCamPHOS·BH3 3f,
65 mg (0.58 mmol) of DABCO and 3 mL of toluene, reac-
tion time 18 h. After chromatographic purification (SiO2,
hexane) 220 mg (0.33 mmol, 84%) of a 1.3:1 mixture of dia-
stereomeric complexes 8a/8b was obtained as a red oil that
further crystallizes in the fridge.
(+)-(1S,4R,6S,8R)-4-Diphenylphosphino-11,11-dimethyl-
5-oxa-3-thiatricyclo[6.2.1.01,6]undecane Borane Complex, ep-
iCamPHOS·BH3 (3d): Prepared according to the general
procedure using 307 mg (1.53 mmol) of oxathiane 1b,
1.3 mL (1.84 mmol) of sec-BuLi 1.4M in cyclohexane,
0.35 mL (1.84 mmol) of chlorodiphenylphosphine and
0.20 mL (1.99 mmol) of BH3·SMe2. The crude product was
purified by flash chromatography (SiO2, Hexanes/AcOEt,
95:5 to 90:10) and the complex epiCamPHOS·BH3 was ob-
tained as a white solid which can be recrystallized in hex-
anes/AcOEt mixtures; yield: 459 mg (1.16 mmol, 73%).
Co2(m-TMS-C2H)(CO)4(m-C25H33OPS) (9a) and (9b): Pre-
pared according to the general procedure using 100 mg
(0.26 mmol) of dicobalt complex (m-TMS-C2H)(CO)6,
100 mg (0.24 mmol) of TolCamPHOS 1g, 40 mg (0.36 mmol)
of DABCO and 4 mL of toluene, reaction time 16 h. After
chromatographic purification (SiO2, hexane/AcOEt 95:5)
165 mg (0.22 mmol, 93%) of a 1:1 mixture of diastereomeric
complexes 7a/7b was obtained as a red foam.
Co2(m-TMS-C2H)(CO)4(m-C23H27OPS) (10a) and (10b):
Prepared according to the general procedure using 100 mg
(0.26 mmol) of dicobalt complex (m-TMS-C2H)(CO)6, 95 mg
Adv. Synth. Catal. 2007, 349, 2121 – 2128
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
2127

Agustí Lledó et al.
FULL PAPERS
(0.24 mmol) of the complex epiCamPHOS·BH3 3h, 40 mg References
(0.36 mmol) of DABCO and 4 mL of toluene, reaction time
16 h. After chromatographic purification (SiO2, hexane/
AcOEt 95:5) 147 mg (0.21 mmol, 86%) of a 2:1 mixture of
diastereomeric complexes 10a/10b was obtained as a red oil.
Co2(m-TMS-C2H)(CO)4(m-C23H39OPS) (11a) and (11b):
Prepared according to the general procedure using 100 mg
(0.26 mmol) of dicobalt complex (m-TMS-C2H)(CO)6, 95 mg
(0.24 mmol) of the complex epiCyCamPHOS·BH3 3i, 40 mg
(0.36 mmol) of DABCO and 4 mL of toluene, reaction time
16 h. After chromatographic purification (SiO2, hexane/
AcOEt 95:5) 76 mg (0.11 mmol, 44%) of a 3.4:1 mixture of
diastereomeric complexes 11a/11b is obtained as a red oil.
[1] X. Verdaguer, A. Moyano, M. A. Pericàs, A. Riera,
M. A. Maestro, J. Mahia, J. Am. Chem. Soc. 2000, 122,
10242.
[2] X. Verdaguer, M. A. Pericàs; A. Riera, M. A. Maestro,
J. Mahia, Organometallics 2003, 22, 1868.
[3] X. Verdaguer, A. Lledó, C. Lopez-Mosquera, M. A.
Maestro, M. A. Pericàs, A. Riera, J. Org. Chem. 2004,
69, 8053.
[4] J. Solà, A. Riera, X. Verdaguer, M. A. Maestro, Orga-
nometallics 2006, 25, 5795.
[5] J. Solà, A. Riera, X. Verdaguer, M. A. Maestro, J. Am.
Chem. Soc. 2006, 128, 13312.
GeneralProcedure for the Catayl tic Pauson–Khand
Reaction
[6] J. Solà, A. Riera, X. Verdaguer, M. A. Maestro, J. Am.
Chem. Soc. 2005, 127, 13629.
[7] M. Iqbal, P. Evans, A. Lledó, X. Verdaguer, M. A. Peri-
càs, A. Riera, C. Loeffler, A. K. Sinha, M. J. Mueller,
ChemBioChem. 2005, 6, 276.
[8] a) T. Shibata, Adv. Synth. Catal. 2006, 348, 2328; b) J.-
M. Muller, A. Rickers, W. Leitner, Adv. Synth. Catal.
2007, 349, 287.
In a pressure Schlenk tube (total volume) fitted with a
teflon screw cap (Kontes HI-VAC) were dissolved
0.650 mmol of alkyne and 0.0325 mmol of the dicobalt com-
plex in 3 mL of toluene. Norbornadiene (132 mL,
1.30 mmol) was then added and the tube quickly purged
with CO. The required working pressure was set up and the
tube closed and heated in an oil bath. After the required re-
action time the volatile components were evaporated and
the crude product was directly purified by flash chromatog-
raphy and analyzed by chiral HPLC (for detailed chromato-
graphic conditions see Ref.[6]).
Crystallographic Data (excluding structure factors) for the
structures reported in this paper have been deposited with
the Cambridge Crystallographic Data Centre and allocated
the deposition no. CCDC-636614 and 636615. Copies of the
data can be obtained free of charge on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax.:
(internat.) (+44)-1223/336-033; e-mail: mailto:depo-
sit@ccdc.cam.ac.uk].
[9] S. Laschat, A. Becheanu, T. Bell, A. Baro, Synlett 2005,
2547.
[10] S. E. Gibson, A. Stevenazzi, Angew. Chem. 2003, 115,
1844; Angew. Chem. Int. Ed. 2003, 42, 1800.
[11] S. E. Gibson, N. Mainolfi, Angew. Chem. 2005, 117,
3082; Angew. Chem. Int. Ed. 2005, 44, 3022.
[12] F. A. Hicks, S. L. Buchwald, J. Am. Chem. Soc. 1999,
121, 7026.
[13] N. Jeong, B. K. Sung, Y. K. Choi, J. Am. Chem. Soc.
2000, 122, 6771.
[14] K. Hiroi, T. Watanabe, R. Kawagishi, I. Abe, Tetrahe-
dron Lett. 2000, 41, 891.
[15] Shibata described the only case of asymmetric intermo-
lecular PKR catalyzed by Ir, see: T. Shibata, K. Takagi,
J. Am. Chem. Soc. 2000, 122, 9852.
[16] The dicobalt alkyne-bridged complexes present fluxion-
ality and may be present in two distinct conformations,
syn and anti, through rotation about the Co-Co bond.
See: Ref.[6] and references cited therein.
Acknowledgements
This work was supported by MEC (CTQ2005–623). X.V.
thanks the DURSI for a “Distinció per a la Promoció de la
Recerca Universitària”. A. L. thanks the MEC for a fellow-
ship; J.S. thanks the DURSI and Universitat de Barcelona for
a fellowship.
[17] G. Coppola, Synth. Commun. 1993, 23, 2003.
2128
asc.wiley-vch.de
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2007, 349, 2121 – 2128