Acetylene - Dicobaltcarbonyl complexes with chiral phosphinooxazoline ligands: Synthesis, structural characterization, and application to enantioselective intermolecular Pauson-Khand reactions

Article abstract of DOI:10.1021/ja001143o

The reaction of the phenylacetylene - dicobalthexacarbonyl complex (2) with the 4-R-2-(2-diphenylphosphinophenyl)oxazolines 1 (R = Ph) and 4 (R = CH₂CH₂SCH₃) leads to the selective formation of the chelated complexes 3 and 5, respectively. On the other hand, the tert-butyl-substituted phosphinooxazoline 6 acts as a monodentate ligand, and its reaction with several 1-alkyne-derived complexes (2,7 - 10) affords readily separable mixtures of the diastereomer nonchelated complexes 11a,b - 15a,b. The interconversion rate between diastereomeric pairs is dependent on the steric bulk of the alkyne substituent, and neither 3 nor 5 epimerize at room temperature. The structures of both kinds of complexes have been ascertained by a combination of spectroscopical (IR, NMR), X-ray diffraction, and chiroptical methods; this has allowed the development of a practical procedure for the establishment of the absolute configuration of the chiral alkyne - dicobaltcarbonyl complexes obtained by the selective substitution of a carbon monoxide on one of the diastereotopic cobalt atoms. The intermolecular Pauson - Khand reaction of the chelated complexes 3 and 5 with norbornadiene respectively affords the (+) and (-) enantiomers of expected enone adduct 25, but in low enantiomeric excesses. Contrary to that, the tertiary amine N-oxide-promoted intermolecular Pauson - Khand reactions of nonchelated complexes 11a,b - 13a,b give the corresponding norbornadiene- or norbornene-derived adducts both in high yields (85-99%) and enantioselectivities (93-97% enantiomeric excess), in what constitutes a substantial improvement over preexisting procedures for this reaction. The possibility of achieving chiral induction in the Pauson - Khand reaction of symmetrical alkynes (via the corresponding dicobaltpentacarbonyl complexes with ligand 6) has been demonstrated for the first time. An enantioselectivity mnemonic rule and a mechanistic model that explains the observed asymmetric sense of induction have been developed, and have been found to be in agreement with the results of model semiempirical molecular orbital calculations.

Full text of DOI:10.1021/ja001143o

7944
J. Am. Chem. Soc. 2000, 122, 7944-7952
Acetylene-Dicobaltcarbonyl Complexes with Chiral
Phosphinooxazoline Ligands: Synthesis, Structural Characterization,
and Application to Enantioselective Intermolecular Pauson-Khand
Reactions
†
,†
†
†
Jaume Castro, Albert Moyano,* Miquel A. Peric a` s, Antoni Riera,
‡
‡
Angel Alvarez-Larena, and Joan F. Piniella
Contribution from Unitat de Recerca en S ´ı ntesi Asim e` trica, Departament de Qu ´ı mica Org a` nica, Facultat
de Qu ´ı mica, UniVersitat de Barcelona, c/Mart ´ı i Franqu e` s, 1-11, 08028-Barcelona, Spain, and Unitat de
Cristal.lografia, Facultat de Ci e` ncies, UniVersitat Aut o` noma de Barcelona, 08193 Bellaterra, Spain
ReceiVed March 31, 2000
Abstract: The reaction of the phenylacetylene-dicobalthexacarbonyl complex (2) with the 4-R-2-(2-
diphenylphosphinophenyl)oxazolines 1 (R ) Ph) and 4 (R ) CH2CH2SCH3) leads to the selective formation
of the chelated complexes 3 and 5, respectively. On the other hand, the tert-butyl-substituted phosphinooxazoline
6
acts as a monodentate ligand, and its reaction with several 1-alkyne-derived complexes (2,7-10) affords
readily separable mixtures of the diastereomer nonchelated complexes 11a,b-15a,b. The interconversion rate
between diastereomeric pairs is dependent on the steric bulk of the alkyne substituent, and neither 3 nor 5
epimerize at room temperature. The structures of both kinds of complexes have been ascertained by a
combination of spectroscopical (IR, NMR), X-ray diffraction, and chiroptical methods; this has allowed the
development of a practical procedure for the establishment of the absolute configuration of the chiral alkyne-
dicobaltcarbonyl complexes obtained by the selective substitution of a carbon monoxide on one of the
diastereotopic cobalt atoms. The intermolecular Pauson-Khand reaction of the chelated complexes 3 and 5
with norbornadiene respectively affords the (+) and (-) enantiomers of expected enone adduct 25, but in low
enantiomeric excesses. Contrary to that, the tertiary amine N-oxide-promoted intermolecular Pauson-Khand
reactions of nonchelated complexes 11a,b-13a,b give the corresponding norbornadiene- or norbornene-derived
adducts both in high yields (85-99%) and enantioselectivities (93-97% enantiomeric excess), in what constitutes
a substantial improvement over preexisting procedures for this reaction. The possibility of achieving chiral
induction in the Pauson-Khand reaction of symmetrical alkynes (via the corresponding dicobaltpentacarbonyl
complexes with ligand 6) has been demonstrated for the first time. An enantioselectivity mnemonic rule and
a mechanistic model that explains the observed asymmetric sense of induction have been developed, and have
been found to be in agreement with the results of model semiempirical molecular orbital calculations.
Introduction
The substitution of one or more carbonyl groups by phos-
phines and related compounds in acetylene-dicobaltcarbonyl
1
complexes has been shown to have significant effects in both
the structure and the reactivity of these synthetically useful
compounds. Thus, it is well-known that trialkyl- and tri-
arylphosphines can readily displace a carbon monoxide molecule
from alkyne-dicobalthexacarbonyls, occupying an axial coor-
dination position in the tetrahedral Co2C2 core, trans to the
cobalt-cobalt bond (Figure 1a), and that this substitution is
accompanied by an appreciable shortening of the cobalt-
Figure 1. Phosphine-substituted alkyne-dicobaltcarbonyl complexes.
carbonyl distances, a fact that is usually ascribed to the poorer
π-acceptor character of phosphines relative to that of carbonyl
2
ligands. In the case of bidentate phosphines, both chelated
*
Author for correspondence. Fax: Int. code + 34933397878. E-mail:
2
a,3
(
Figure 1b) and bridged (Figure 1c) complexes in which the
amoyano@qo.ub.es.
†
‡
ligand occupies equatorial coordination positions about the metal
atoms have been obtained.
Universitat de Barcelona.
Universitat Aut o` noma de Barcelona.
(1) For reviews on alkyne-dicobaltcarbonyl complexes, see: (a) Schore,
N. E. Chem. ReV. 1988, 88, 1081-1119. (b) Hegedus, L. S. Transition
Metals in the Synthesis of Complex Organic Molecules; University Science
Books: Mill Valley, CA, 1994; chapter 8. (c) Caffyn, A. J. M.; Nicholas,
K. M. In ComprehensiVe Organometallic Chemistry II; Abel, E. W., Stone,
F. G., Wilkinson, G., Eds.; Elsevier: New York, 1995; Vol. 12, pp 685-
(2) (a) Chia, S.; Cullen, W. R.; Franklin, M.; Manning, A. R. Inorg.
Chem. 1975, 14, 2521-2526. (b) V a´ radi, G.; Vizi-Orosz, A.; Vastag, S.;
P a´ lyi, G. J. Organomet. Chem. 1976, 108, 225-233. (c) Bonnet, J.-J.;
Mathieu, R. Inorg. Chem. 1978, 17, 1973-1976. (d) Hughes, R. P.; Doig,
S. J.; Hemond, R. C.; Smith, W. L.; Davis, R. E.; Gadol, S. M.; Holland,
K. D. Organometallics 1990, 9, 2745-2753. (e) Jeffery, J. C.; Pereira, R.
M. S.; Vargas, M. D.; Went, M. J. J. Chem. Soc., Dalton Trans. 1995,
1805-1811.
7
02. (d) Schore, N. E. In ComprehensiVe Organometallic Chemistry II; Abel,
E. W., Stone, F. G., Wilkinson, G., Eds.; Elsevier: New York, 1995; Vol.
2, pp 703-739.
1
1
0.1021/ja001143o CCC: $19.00 © 2000 American Chemical Society
Published on Web 08/08/2000

Acetylene-Dicobaltcarbonyl Complexes
J. Am. Chem. Soc., Vol. 122, No. 33, 2000 7945
With regard to reactivity, phosphine-substituted acetylene-
Scheme 1
dicobaltcarbonyl complexes have been studied in connection
4
5,6
to both the Nicholas and the Pauson-Khand reactions, mainly
with the aim of developing enantioselective versions of these
processes. Up to now, however, complexes of this type have
not found extensive use in synthesis, due to several reasons:
(a) In several instances, because of the stereoheterotopic
nature of the two cobalt atoms, phosphine substitution on
acetylene-dicobalthexacarbonyl complexes leads to the forma-
tion of diastereomer pairs, which are often hardly separable.
This happens for example in complexes of the type shown in
1
2
Figure 1a (with R different from R ), either when the phosphine
ligand or the alkyne moiety is chiral. Even when obtained
stereoisomerically pure, the absolute configuration of such
substituted complexes is difficult to ascertain by methods other
than X-ray diffraction. Thus, lack of crystallinity has prevented
the complete characterization of the (R)-Glyphos-derived com-
We have recently found9 that the reaction of (R)-2-(2-
diphenylphosphinophenyl)-4-phenyloxazoline 1 with the phen-
ylacetylene-dicobalthexacarbonyl complex (2) gives rise to a
5:15 mixture of two diastereomer complexes. The structure
of the major one (3), elucidated by X-ray diffraction analysis,
revealed an unprecedented P,N-chelation of the ligand with one
cobalt atom (Scheme 1).
8
6
a,d
plexes used in enantioselective Pauson-Khand reactions.
b) Thermally induced phosphine dissociation processes,
(
leading to the interconversion between stereoisomeric complexes
and to the loss of the stereochemical integrity of the tetrahedral
C2Co2 moiety, take place at relatively low temperatures. This
phenomenon strongly limits the use of enantiopure chiral
phosphine-substituted alkyne complexes in asymmetric Pauson-
Khand and Nicholas reactions.
Contrary to nonchelated, phosphine-substituted alkyne-
dicobaltcarbonyl complexes, 3 was very stable toward isomer-
ization, but showed only moderate enantioselectivities [up to
5
1% enantiomeric excess (ee)] in the intermolecular Pauson-
Khand reaction with norbornadiene. On the basis of these
findings, we decided to further investigate the use of 4-substituted-
(
c) The electrophilicity of dicobaltcarbonyl-stabilized pro-
2
-(2-diphenylphosphinophenyl)oxazolines as chiral ligands for
pargyl cations, which are the reactive intermediates in the
Nicholas reaction, is greatly diminished upon substitution of a
alkyne-dicobaltcarbonyl complexes. We disclose here in full
detail the results of this study, which has led to the development
of both a highly enantioselective, practical version of the
intermolecular Pauson-Khand reaction and a facile method for
the determination of the absolute configuration of chiral,
phosphine-substituted acetylene-dicobaltcarbonyl complexes.
7
carbon monoxide by a triaryl- or trialkylphosphine. In a similar
way, the Pauson-Khand reactivity of phosphine- or phosphite-
substituted complexes is lower than that of the parent unsub-
stituted compounds.6
f,8
(
3) (a) Gelling, A.; Jeffery, J. C.; Povey, D. C.; Went, M. J. J. Chem.
Results and Discussion
Soc., Chem. Commun. 1991, 349-351. (b) Gelling, A.; Went, M. J.; Povey,
D. C. J. Organomet. Chem. 1993, 455, 203-210. (c) Mirza, H. A.; Vittal,
J. J.; Puddephatt, R. J.; Frampton, C. S.; Manojlovic-Muir, L.; Xia, W.;
Hill, R. H. Organometallics 1993, 12, 2767-2776. (d) Yang, K.; Bott, S.
G.; Richmond, M. G. Organometallics 1995, 14, 4977-4979. (e) Yang,
K.; Bott, S. G.; Richmond, M. G. J. Organomet. Chem. 1996, 516, 65-80.
Synthetic and Structural Studies on Alkyne-Dicobalt-
phosphinooxazoline)carbonyl Complexes. First, we studied
(
the reaction of the methionine-derived phosphinooxazoline 4
prepared from (S)-methioninol according to the procedure
[
(
f) Edwards, A. J.; Mach, S. R.; Mays, M. J.; Mo, C.-Y.; Raithby, P. R.;
10
reported by Helmchen and co-workers ] with the phenylacety-
lene-dicobalthexacarbonyl complex 2. The oxazoline residue
was chosen to ascertain the effect of the replacement of the
phenyl group in 1 by a less bulky alkyl chain, as well as to
investigate the possibility of additional chelation by the sulfide
Rennie, M.-A. J. Organomet. Chem. 1996, 519, 243-251. (g) Gimbert,
Y.; Robert, F.; Durif, A.; Averbuch, M.-T.; Kann, N.; Greene, A. E. J.
Org. Chem. 1999, 64, 3492-3497.
(
4) (a) Nicholas, K. M. Acc. Chem. Res. 1987, 20, 207-214. (b) Bradley,
D. H.; Khan, M. A.; Nicholas, K. M. Organometallics 1989, 8, 554-556.
c) D’Agostino, M. F.; Frampton, C. S.; McGlinchey, M. J. Organometallics
(
1
1
1
1
1
990, 9, 2972-2984. (d) Dunn, J. A.; Pauson, P. L. J. Organomet. Chem.
991, 419, 383-389. (e) Bradley, D. H.; Nicholas, K. M. Organometallics
992, 11, 2598-2607. (f) Caffyn, A. J. M.; Nicholas, K. M. J. Am. Chem.
moiety. The treatment of 2 with 1 equiv of 4 in hot toluene
led to the isolation of a new complex 5 in 78% yield after
chromatographic purification (Scheme 2).
Soc. 1993, 115, 6438-6439.
(
5) Reviews on the Pauson-Khand reaction: (a) Pauson, P. L.; Khand,
I. U. Ann. N. Y. Acad. Sci. 1977, 295, 2-14. (b) Pauson, P. L. Tetrahedron
985, 41, 5855-5860. (c) Schore, N. E. Org. React. 1991, 40, 1-90. (d)
This complex appears to be a single diastereomer, according
to physical data (melting point), chromatographic behavior
1
Schore, N. E. In ComprehensiVe Organic Synthesis; Trost, B. M., Ed.;
Pergamon Press: Oxford, 1991; Vol. 5, pp 1037-1064. (e) Geis, O.;
Schmalz, H. G. Angew. Chem., Int. Ed. Engl. 1998, 37, 911-914. (f)
Buchwald, S. L.; Hicks, F. A. In ComprehensiVe Asymmetric Catalysis;
Jacobsen, E. N., Pfaltz, A., Yamamoto, H., Eds.; Springer: Berlin, 1999;
Vol. II, pp 491-510.
(8) Billington, D. C.; Helps, I. M.; Pauson, P. L.; Thomson, W.; Willison,
D. J. Organomet. Chem. 1988, 354, 233-242.
(9) Castro, J.; Moyano, A.; Peric a` s, M. A.; Riera, A.; Alvarez-Larena,
A.; Piniella, J. F. J. Organomet. Chem. 1999, 585, 53-58.
(10) Peer, M.; Jong, J. C.; Kiefer, M.; Langer, T.; Rieck, H.; Schell, H.;
Sennhenn, P.; Sprinz, J.; Steinhagen, H.; Wiese, B.; Helmchen, G.
Tetrahedron 1996, 52, 7547-7583.
(6) (a) Bladon, P.; Pauson, P. L.; Brunner, H.; Eder, J. J. Organomet.
Chem. 1988, 353, 449-454. (b) Brunner, H.; Niederhuber, A. Tetrahe-
dron: Asymmetry 1990, 1, 711-714. (c) Park, H.-J.; Lee, B. Y.; Kang, Y.
K.; Chung, Y. K. Organometallics 1995, 14, 3104-3107. (d) Hay, A. M.;
Kerr, W. J.; Kirk, G. G.; Middlemiss, D. Organometallics 1995, 14, 4986-
(11) (a) Krafft, M. E. J. Am. Chem. Soc. 1988, 110, 968-970. (b) Krafft,
M. E.; Juliano, C. A.; Scott, I. L.; Wright, C.; McEachin, M. D. J. Am.
Chem. Soc. 1991, 113, 1693-1703. (c) Krafft, M. E.; Juliano, C. A. J.
Org. Chem. 1992, 57, 5106-5115. (d) Krafft, M. E.; Scott, I. L.; Romero,
R. H.; Feibelmann, S.; Van Pelt, C. E. J. Am. Chem. Soc. 1993, 115, 7199-
7207. (e) Verdaguer, X.; Moyano, A.; Peric a` s, M. A.; Riera, A.; Bernardes,
V.; Greene, A. E.; Alvarez-Larena, A.; Piniella, J. F. J. Am. Chem. Soc.
1994, 116, 2153-2154. (f) Tormo, J.; Verdaguer, X.; Moyano, A.; Peric a` s,
M. A.; Riera, A. Tetrahedron 1996, 52, 14021-14040. (g) Verdaguer, X.;
V a´ zquez, J.; Fuster, G.; Bernardes-G e´ nisson, V.; Greene, A. E.; Moyano,
A.; Peric a` s, M. A.; Riera, A. J. Org. Chem. 1998, 63, 7037-7052. (h)
Montenegro, E.; Poch, M.; Moyano, A.; Peric a` s, M. A.; Riera, A.
Tetrahedron Lett. 1998, 39, 335-338.
4
988. (e) Kerr, W. J.; Kirk, G. G.; Middlemiss, D. J. Organomet. Chem.
996, 519, 93-101. (f) Derdau, V.; Laschat, S.; Dix, I.; Jones, P. G.
1
Organometallics 1999, 18, 3859-3864. For the use of chiral bidentate
phosphines in catalytic asymmetric intramolecular Pauson-Khand reactions,
see: (g) Hiroi, K.; Watanabe, T.; Kawagishi, R.; Abe, I. Tetrahedron Lett.
2
000, 41, 891-895. (h) Hiroi, K.; Watanabe, T.; Kawagishi, R.; Abe, I.
Tetrahedron: Asymmetry 2000, 11, 797-808.
7) Kuhn, O.; Rau, D.; Mayr, H. J. Am. Chem. Soc. 1998, 120, 900-
07.
(
9

7946 J. Am. Chem. Soc., Vol. 122, No. 33, 2000
Castro et al.
Scheme 2
HPLC), and spectroscopic studies ( H and 13C NMR). Because
1
(
we were not able to obtain single crystals suitable for X-ray
diffraction analysis, the structural characterization of 5 was
carried out in the following way. First, the 1:1 stoichiometry
of the new complex was readily apparent both from the NMR
spectra and from mass spectroscopic data. Next, the fact that
the phosphinooxazoline 4 acts as a bidentate ligand in complex
Figure 2. CD spectra of pseudoenantiomeric complexes 3 and 5.
Scheme 3
5
could be established by inspection of infrared (IR) spectrum
of 5, both in the carbonyl (see later) and in the CdN stretching
zones; in effect, a shift of this band from 1655 (in the free ligand
-
1
4
) to 1625 cm (in the complex) is strongly indicative of the
9
presence of a chelated structure, as previously observed by us
and by other authors.12 On the other hand, complexation of the
cobalt by the sulfur atom of the chain does not take place in 5,
as revealed by the coincidence of the H and C NMR signals
corresponding to methylthioethyl group in both 4 and 5.
Finally, the absolute configuration of 5 was ascertained by
1
13
Table 1. Synthesis of Dicobalt Pentacarbonyl Complexes
1
1a,b-15a,b
1
3
analysis of its chiroptical properties. Previously, Kajt a` r et al.
starting
reaction
have shown that the circular dichroism (CD) spectra of the
dicobalthexacarbonyl complexes of chiral acetylenes show
several bands in the 300-600-nm zone that can be assigned to
chirally perturbed transitions of the C2Co2(CO)6 core of the
molecule. We reasoned that the CD spectra of complexes such
as 3 and 5, in which the local C2v symmetry of the C2Co2
tetrahedral moiety is broken by the substitution of one cobalt
atom, would exhibit a direct correlation with the absolute
configuration of the molecule. After checking that the free
ligands 1 and 4 did not present any significant absorption in
the CD between 300 and 700 nm, we recorded the spectra of
the corresponding complexes 3 and 5, which as anticipated
showed relatively intense bands ascribable to transitions of the
intrinsically chiral C2Co2 chromophore (Figure 2).
entry
complex
Ph (2)
nBu (7)
SiMe (8)
t-Bu (9)
conditionsa
product (yield, %)b
d.r.c
1
2
3
4
5
60 °C, 2.5 h 11a (38), 11b (39) 1:1.02
55 °C, 1 h
60 °C, 2 h
70 °C, 3 h
12a (34), 12b (47) 1:1.24
13a (14), 13b (16) 1:1.33
14a (16), 14b (21) 1:1.25
3
CH OH (10) 55 °C, 2.5 h 15a (28), 15b (16) 1.87:1
2
a
Stirring the preformed complex in toluene solution at the specified
temperature in the presence of 1 molar equiv of the phosphinooxazoline
6 under nitrogen. b Yield of diastereomerically pure, isolated complexes
c
after column chromatography (SiO
of the reaction mixture.
2
). Determined by HPLC analysis
entry 1 of Table 1). After heating a 1:1 mixture of 2 and 6 at
0 °C in toluene for 2.5 h, thin-layer chromatography (TLC)
6
analysis showed the complete disappearance of complex 2 and
the presence of two more polar, dark-colored spots of similar
intensity. After chromatographic purification, the two mono-
substituted complexes 11a and 11b were isolated as burgundy-
colored, crystalline solids in 38 and 39% yield, respectively.
The spectral data of both 11a and 11b clearly showed their
diastereomeric nature. The structure of the more polar complex
As can readily be seen, the two spectra present a clear
pseudoenantiomeric relation. Because the X-ray analysis of 3
established that the phosphinooxazoline ligand is chelating the
pro-R cobalt atom, we conclude that in complex 5 the coordina-
tion of the ligand takes place at the pro-S cobalt, as depicted in
Scheme 2. It is thus clear that the stereochemistry of these
chelated complexes is dictated by the absolute configuration of
the chiral oxazoline moiety: the phosphinooxazoline ligand 1
1
1b was unambiguously determined by X-ray diffraction of a
single crystal, and is shown in Figure 3.
[derived from (R)-phenylglycinol] leads to an (R)-configuration
of the C2Co2 moiety in complex 3, whereas the (S)-ligand 4
affords the corresponding (S)-complex 5.
To further clarify the influence of the steric bulk of the
oxazoline substituent, we next studied the reaction of 2 with
the (S)-t-leucinol-derived10 phosphinooxazoline 6 (Scheme 3 and
Contrary to what we had observed for complexes 3 and 5, in
this case the phosphinooxazoline behaves as a monodentate
ligand, in which the phosphorus atom is bound to the pro-R
cobalt atom in an axial (i.e., trans to the cobalt-cobalt bond)
coordination position. The cobalt-cobalt and cobalt-carbon
bond lengths of the C2Co2 core are similar to those of
(
12) Koch, G.; Lloyd-Jones, G. C.; Loiseleur, O.; Pfaltz, A.; Pr e´ t oˆ t, R.;
Schaffner, S.; Schnider, P.; Von Matt, P. Recl. TraV. Chim. Pays-Bas 1995,
14, 206-210.
13) Kajt a´ r, M.; K a´ jtar-Miklos, J.; Giacomelli, G.; Ga a´ l, G.; V a´ radi, G.;
Horv a´ th, I. T.; Zucchi, C.; P a´ lyi, G. Tetrahedron: Asymmetry 1995, 6,
177-2194.
14
unsubstituted complexes, whereas the cobalt-phosphorus bond
length and the Co-Co-P and C-Co-P bond angles are
1
(
(14) Castro, J.; Moyano, A.; Peric a` s, M. A.; Riera, A. Tetrahedron 1995,
51, 6541-6556.
2

Acetylene-Dicobaltcarbonyl Complexes
J. Am. Chem. Soc., Vol. 122, No. 33, 2000 7947
Scheme 4
Figure 3. Molecular structure of 11b in solid state. Hydrogen atoms
have been omitted for clarity.
analogous to those recorded for other phosphine-substituted
complexes.2 On the other hand, the usual decrease of the
cobalt-carbonyl distances upon substitution of a carbonyl ligand
by a poorer π-acceptor one is also observed in this case. As
we will see later, the structure of the less polar complex 11a is
totally parallel to that of 11b, except for the fact that the ligand
is bound to the pro-S cobalt atom.
On the basis of this result, we explored the effect of the alkyne
substituent by reacting 6 with the alkyne-dicobalthexacarbonyl
complexes 7-10 (Scheme 3 and entries 2-5 in Table 1). In all
instances, an easily separable mixture of two monosubstituted,
nonchelated diastereomer complexes (12a,b-15a,b) was ob-
tained. This demonstrates that the presence of the bulky tert-
butyl substituent in the oxazoline moiety strongly hinders the
formation of a chelated complex, the ligand 6 acting as a
monodentate chiral phosphine, but with the additional bonus
that the two diastereomers can be separated by standard column
,3
2c
both diastereomers of complex 11 appear to be remarkably
stable, since the diastereomeric purity of a hexane solution of
1
1b remained essentially unchanged after 2 days at room
temperature, whereas that of 11a was slightly disminished (6%
loss). Complexes 12a and 12b interconvert slowly at room
temperature (a 11% loss of the diastereomeric purity of a
solution of 12a was observed after 2 days). The behavior of
1
5a,b is very similar to that of 12a,b, except that the stability
of these complexes in solution is much more limited. The
trimethylsilyl-substituted complexes 13a,b epimerize more
readily, and a 6% loss of diastereomeric excess is observed after
1
1
h. In sharp contrast to this, the tert-butyl-substituted complexes
4a,b undergo a very fast interconvertion, and their diastereo-
meric excesses fall down to ca. 70% after 1 h at room
temperature. On the other hand, the chelated complex 3 does
chromatography, being readily obtained in high diastereomeric
9
purity (checked by HPLC).15 The nature of the acetylene
not epimerize at room temperature. As we will see later, the
relative rates of epimerization of these complexes are closely
related to the enantioselectivities of their Pauson-Khand
reactions.
substituent has some effect both in the yield and in the
stereoselectivity of the process. Thus, in the case of the
phenylacetylene (2)- and of the 1-hexyne (7)-derived complexes,
the reaction was not diastereoselective (entries 1 and 2 in Table
The behavior of symmetrical alkyne-dicobalthexacarbonyl
complexes toward the substitution reaction was also investigated.
In this case, given the homotopic nature of the two cobalt atoms,
only one monosubstituted complex can be obtained. The reaction
of the ethyne complex 16 with 1 equiv of the phosphinooxazo-
line 6 gave a four-component mixture (TLC) from which the
monosubstituted complex 17 could be isolated in 42% yield by
column chromatography (Scheme 4). The nonchelated nature
of 17 was deduced from its spectroscopic properties (see below).
The diphenylacetylene-derived complex 18 reacted more slug-
gishly with 6, and gave, after heating in toluene at 70 °C over
3 h, a mixture of the nonchelated, monosubstituted complex 19
with an unstable, less polar complex 20 to which we assigned
a chelated structure (Scheme 4). Although the unstability of 20
precluded its spectroscopic characterization, this structural
assignment comes from the fact that pure complex 19, isolated
in 55% yield by column chromatography, could be completely
converted into 20 either by heating at 90 °C or by treatment by
1
). Increasing the steric bulk of the alkyne substituent (com-
plexes 8 and 9) strongly diminished the yield of the reaction,
whereas the isomer ratio remained essentially the same (entries
3
and 4 in Table 1). A reversal of the diastereoselectivity of
the process was observed with the 1-propynol-derived complex
0, which gave a ca. 1.9:1 mixture in which the less polar
1
complex was the major component (entry 5 of Table 1). In this
case, the relatively low global yield (44%) was due to the
competing formation of other complexes that were too unstable
to be characterized.
The easy availability of the complexes in stereochemically
pure form allowed us to investigate their stability toward
epimerization processes. To this end, all of the isolated
complexes were dissolved in hexane at room temperature
immediately after chromatographic purification and the diaster-
eomeric purity of the resulting solutions was monitored by
HPLC (see Supporting Information). The rate of epimerization
is dependent on the steric bulk of the alkyne substituent. Thus,
1
1
N-methylmorpholine-N-oxide.
Whereas the structure of 11b was unambiguously established
by X-ray diffraction, those of the remaining complexes derived
from phosphinooxazoline 6 (11a, 12a,b-15a,b, 17, and 19)
(
15) The separation of the diastereomer alkyne-dicobaltpentacarbonyl
complexes obtained by substitution with (R)-Glyphos has only been achieved
either by fractional crystallization or by preparative HPLC.
6
a,b
6d,e

7948 J. Am. Chem. Soc., Vol. 122, No. 33, 2000
Castro et al.
Figure 4. CD spectra of diastereomer complexes (a) 11a,b; (b) 12a,b; (c) 13a,b; and (d) 15a,b.
1
were ascertained by indirect methods. In the course of the
structure determination process, three questions have to be
answered: (a) Is the phosphinooxazoline 6 acting as a mono-
or as a bidentate (chelated or bridged) ligand? (b) Is the
phosphorus atom placed in an axial or in an equatorial
coordination site? (c) In the case of complexes derived from
nonsymmetrical alkynes, which of the two enantiotopic cobalt
atoms has been substituted?
1655 cm- that corresponds to the CdN stretching frequency
of the free ligand.
Chiroptical Method for Assigning Absolute Configuration
of the C2Co2 Moiety in Chiral Phosphine-Substituted Alkyne-
Dicobaltcarbonyl Complexes. The absolute configuration of
the chiral alkyne-dicobaltcarbonyl complexes obtained by the
selective substitution of a carbon monoxide on one of the
diastereotopic cobalt atoms has been ascertained only in the
The nonchelated nature of the complexes could be readily
ascertained by inspection of their IR spectra. Because the
structures of both 3 and 11b are known from X-ray diffraction
studies, we can conclude that the intramolecular coordination
of one cobalt by the oxazoline nitrogen is accompanied by a
cases in which the X-ray diffraction analysis has been possible.9
Our finding that the sign of several bands of the CD spectra of
the chelated complexes 3 and 5 appeared to present a clear
correlation with their absolute configurations paved the way for
the development of a practical alternative to X-ray diffraction.
In particular, in the case of complex 3, in which the configu-
ration of the C2Co2 moiety is (R), the CD spectrum presents a
maximum (∆ꢀ ) + 7.9) at a wavelength of 475 nm, whereas
the (S)-complex 5 showed a minimum negative absorption (∆ꢀ
-
1
decrease of ca. 40 cm of the frequencies associated with CO
stretching vibrations. These experimental observations are
moreover in good accordance with theoretical calculations on
the normal vibration models of model complexes, performed
with the PM3(tm) semiempirical method16 as implemented in
the SPARTAN 5.1.1 package of programs17 (see Supporting
Information). Moreover, as we have already stated when
discussing the structure of complex 5, the position of the CdN
stretching band is also indicative of the coordination mode of
the phosphinooxazoline ligand. Thus, all of the nonchelated
complexes (11a,b-15a,b, 17, 19) present an IR absorption at
)
- 3.8) at a very similar wavelength (Figure 2). We surmised
that in the case of the monosubstituted (1-alkyne)-dicobalt-
pentacarbonyl complexes the sign of a CD absorption at ca.
5
(
00 nm, if observed, could also be directly related to the topicity
i.e., to the pro-R or the pro-S character) of the substituted cobalt.
To verify this hypothesis, we measured the CD spectra of
the complexes 11a,b-13a,b and 15a,b (Figure 4). All of them
presented several bands in the 300-700-nm zone. Most
importantly, we were pleased to find that the complex 11b,
whose (R) configuration at the C2Co2 moiety had been unam-
biguously established by X-ray diffraction analysis (Figure 3),
(
16) Which incorporates a parametrization for transition metals to the
original PM3 method: Stewart, J. J. P. J. Comput. Chem. 1989, 10, 209-
20.
17) SPARTAN, version 5.1.1. Wavefunction, Inc.; 18401 Von Karman
Ave., Suite 370, Irvine, CA 92612.
2
(

Acetylene-Dicobaltcarbonyl Complexes
J. Am. Chem. Soc., Vol. 122, No. 33, 2000 7949
Table 2. Intermolecular Pauson-Khand Reaction of Complexes 5,
1
1a,b, 13a,b, and 15a,b with Norbornadiene
starting
complex
reaction
entry
conditionsa
26b product yieldc eed
1
2
3
4
5
6
7
8
9
Ph (5)
Ph (5)
A, 60 °C, 18 h
B, 20 °C, 24 h
A, 60 °C, 18 h
A, 45 °C, 18 h
B, 20 °C, 24 h
B, 0 °C, 24 h
A, 80 °C, 15 min
A, 45 °C, 18 h
B, 0 °C, 24 h
-
(-)-21
21
(-)-21
(-)-21
93
90
86
98
85
85
95
98
99
73
89
54
92
33
50
12
0
n.d.
-
-
n.d. (-)-21
87
-
Ph (11a)
Ph (11a)
Ph (11a)
Ph (11a)
Ph (11b)
Ph (11b)
Ph (11b)
nBu (12a)
nBu (12b)
61
66
87
94
70
74
97
82
93
83
95
30
19
(-)-21
(+)-21
(+)-21
-
n.d. (+)-21
10
11
12
13
14
15
B, 20 °C, 24 h
B, 20 °C, 24 h
88
85
70
94
92
85
(-)-22
(+)-22
(-)-23
(+)-23
(-)-24
(+)-24
Figure 5. Empirical rule for determination of the absolute configuration
of chiral phosphine-substituted 1-alkyne-dicobaltcarbonyl complexes
using their chiroptical properties.
CH
CH
2
OH (15a) B, 20 °C, 24 h
OH (15b) B, 20 °C, 24 h
2
SiMe
SiMe
3
(13a)
(13b)
B, 20 °C, 24 h
B, 20 °C, 24 h
3
Scheme 5
a
(A) stirring the preformed complex in toluene solution at the
specified temperature in the presence of 10 equiv of olefin under
nitrogen; (B) chemical activation of the complex by N-methylmorpho-
b
line-N-oxide in dichloromethane solution under nitrogen. Yield (%)
c
of phosphine oxide 26 (see text). Yield (%) of isolated product after
chromatographic purification. d Determination of the enantiomeric purity
(% ee) of 21 and 23 by HPLC analysis. Determination of the
enantiomeric purity (% ee) of 22 and 24 by GC analysis.
enantioselectivity (61% ee). Lowering the reaction temperature
to 45 °C (entry 4) gave slightly better yield and optical purity.
A substantial improvement took place when the reaction was
promoted by N-methylmorpholine-N-oxide: at 0 °C, enone (-)-
showed a maximum positive dichroism at 492 nm (∆ꢀ ) +
4
.4), and that its diastereomer 11a had a CD spectrum
pseudoenantiomeric to that of 11b (Figure 4a), with a minimum
at 480 nm (∆ꢀ ) - 3.8). In all of the remaining complex pairs,
the more polar ones (12b, 13b, 15b) have a positive CD in the
2
1 was obtained in 85% yield and in high enantiomeric purity
(94% ee, entry 6). Under these optimized conditions (entry 9),
the diastereomer complex 11b produced the dextrorotatory
adduct (+)-21, again with high optical purity (97% ee) and in
essentially quantitative yield. The use of thermal activation
4
50-650-nm region that presents a mirror-image relation with
the CD spectra of the corresponding less polar diastereomers
12a, 13a, 15a, Figure 4b-d). In this way, we have shown for
(
(entries 7 and 8) diminished the enantiomeric excess of the
the first time that the absolute configuration of chiral, phosphine-
substituted 1-alkyne-dicobaltcarbonyl complexes can be di-
rectly ascertained from their chiroptical properties according
to the following empirical rule: A positiVe (negatiVe) CD
absorption in the 450-650-nm region implies that the phosphine
ligand is bound at the pro-R (pro-S) cobalt atom (Figure 5).
Enantioselective Intermolecular Pauson-Khand Reac-
tions of Chiral Phosphinooxazoline-Substituted Alkyne-
Dicobaltcarbonyl Complexes. Having successfully solved the
problem of the structure elucidation of the phosphinooxazoline-
substituted complexes, we turned our attention to their inter-
molecular Pauson-Khand reactions. In the first place, we
studied their reaction with norbornadiene (Scheme 5 and Table
product. Thus, both enantiomers of the exo-tricyclic ketone 21
can be obtained from the same starting materials (2, 6, and
norbornadiene).
These excellent results could be extended to other alkyne
complexes. Thus, the two diastereomer complexes derived from
1
-hexyne (12a and 12b) gave rise, respectively, to the levo-
and dextrorotatory enantiomers of the exo-enone 22 in high
optical purity (entries 10 and 11). In a similar way, the reaction
of the diastereomer complexes derived from propargyl alcohol
(15a and 15b) took place in a highly enantioselective fashion
(entries 12 and 13), affording the two enantiomers of the tricyclic
exo-keto alcohol 23. For these complexes, the reaction was run
at 20 °C, because lowering the temperature at 0 °C resulted in
very low conversions. On the other hand, the Pauson-Khand
reaction of the two complexes derived from trimethylsilylethyne
(13a and 13b) was very slow, and the levo- and dextrorotatory
enantiomers of the expected exo-adduct 24 were obtained in
both low yields and enantiomeric excesses (entries 14 and 15).
In this case, TLC monitoring of the reaction mixture showed
that epimerization processes compete with the Pauson-Khand
reactions, in accordance with the epimerization behavior
observed by HPLC. It is thus clear that, as was originally
2
).
The reaction of complex 5 with norbornadiene gave, under
thermal conditions (entry 1 of Table 2), the levorotatory exo-
enone (-)-21 in a low enantiomeric excess (12% ee). When
the reaction was run in the presence of N-methylmorpholine-
18
N-oxide, essentially racemic 21 was obtained (entry 2 of Table
). This behavior is entirely parallel to that observed in the case
2
9
of 3, and underscores the fact that chelated complexes, although
being very stable toward epimerization processes, give low
enantioselectivities in the Pauson-Khand reaction.
6a
suggested, the intermolecular Pauson-Khand reactions of the
pure diastereomers are stereospecific, and that the only requisite
for attaining good enantioselectivities is that the rate of
cycloaddition must be much higher than that of epimerization.
The reaction of complexes 11a,b with norbornene, under
N-methylmorpholine-N-oxide-promoted conditions, was also
investigated (Scheme 6 and Table 3). Optimization of the
temperature (0 °C) led to the formation of the two enantiomers
The reaction took a very different course in the case of the
nonchelated complexes. The thermal reaction (toluene, 60 °C)
of the phenylacetylene-derived complex 11a (entry 3) afforded
the adduct (-)-21 in high yield (86%) and with moderate
(18) (a) Shambayati, S.; Crowe, W. E.; Schreiber, S. L. Tetrahedron
Lett. 1990, 31, 5289-5292. (b) Jeong, N.; Chung, Y. K.; Lee, B. Y.; Lee,
S. H.; Yoo, S.-E. Synlett 1991, 204-206.

7950 J. Am. Chem. Soc., Vol. 122, No. 33, 2000
Castro et al.
Scheme 6
Scheme 7
NMO, CH
Cl2
2
Table 3. Intermolecular Pauson-Khand Reaction of Complexes
1
1a,b with Norbornene
starting
entry complex
reaction
conditions
a
26b product yieldc eed
1
2
3
4
5
Ph (11a) 20 °C, 18 h
Ph (11a) 0 °C to 20 °C, 24 h 90
Ph (11b) 20 °C, 18 h
Ph (11b) 0 °C to 20 °C, 24 h 79
Ph (11b) 0 °C, 24 h 86
n.d. (-)-25
91
89
83
77
85
68
74
67
87
94
(c) The ultimate source of chirality (tert-leucinol) can be
recovered at the end of the process.
(-)-25
n.d. (+)-25
(d) Because the absolute configurations of both the starting
(+)-25
(+)-25
complexes and (as we will see in the next section) of the reaction
products can be ascertained, the stereochemical course of the
reaction can be determined.
a
Chemical activation of the complex 11a,b by N-methylmorpholine-
b
N-oxide in dichloromethane solution under oxygen. Yield (%) of
phosphine oxide 26 (see text). Yield (%) of isolated product after
chromatographic purification. Determination of the enantiomeric purity
% ee) of 25 by HPLC analysis.
Finally, we set out to investigate the hitherto unexplored
possibility of performing an enantioselective Pauson-Khand
reaction with symmetrical alkynes. The N-methylmorpholine-
N-oxide-promoted reaction of the acetylene complex 17 with
norbornadiene (Scheme 7) gave a readily separable mixture of
c
d
(
of the expected exo-enone 25 with yields and enantiomeric
purities only slightly inferior to those obtained when using
norbornadiene (compare entries 2 and 5 of Table 3 with entries
and 9, respectively, of Table 2).
Another interesting feature of this reaction lies in the fact
2
0
the exo- and endo-adducts (-)-27 and 28 in 53 and 9% yield,
respectively. Most significantly, the major adduct was obtained
in nonracemic form (29% ee, as determined by chiral GC).21
Even if the recorded enantioselectivities are only moderate,
the above results stand out as the first examples of an
enantioselective Pauson-Khand reaction with symmetrically
substituted alkynes.
6
that the ultimate source of chirality [(S)-tert-leucinol] can be
recovered at the end of the process in good yield. In effect,
when the Pauson-Khand reaction was run in the presence of
N-methylmorpholine-N-oxide, the phosphine oxide 26 derived
from 6 could be isolated by column chromatography (70-94%
yields; see Tables 2 and 3). Subsequent acidic hydrolysis of 26
afforded pure (S)-tert-leucinol in 85% yield. It is worth noting
that under thermal conditions the phosphinooxazoline ligand
appears to be strongly bonded to the cobalt residues, and was
not recovered from the reaction mixture.
In conclusion, the above results show that the (S)-phosphi-
nooxazoline 6 is an exceptionally good chiral ligand in the
enantioselective intermolecular Pauson-Khand reactions of
relatively unhindered 1-alkynes that nicely complements the
chiral auxiliary-based strategies previously developed in our
laboratories.1 Moreover, the use of 6 presents several clear-
cut advantages over the preexisting methods also based on the
use of chiral phosphines:6
Determination of Absolute Configuration of Reaction
Products. 1. Enantioselectivity Mnemonic for Intermolecular
Pauson-Khand Reaction of Phosphine-Substituted Alkyne
Complexes. In previous reports on chiral phosphine-mediated
6a-e
enantioselective Pauson-Khand reactions,
not only were the
absolute configurations of the starting complexes unknown, but
those of the adducts do not appear to have been investigated.
As a result of that, the stereochemical course of these reactions
remained totally unclear.
In the course of our studies on the Pauson-Khand reaction
of chiral 1-alkynylsulfoxides, we had established that the
absolute configuration of enones (-)-22 was (1R,2R,6R,7S) and
1,19
22
that (+)-25 had the opposite (1S,2S,6S,7R) configuration. In
the present work, we were able to assign the absolute stereo-
chemistry of enones (-)-24 and (-)-27 in the following way
Scheme 8): Catalytic hydrogenation of (-)-24 (30% ee)
afforded the levorotatory R-trimethylsilyl ketone (-)-29, which
after desilylation gave the levorotatory exo-tricyclic ketone (-)-
0. This compound showed a negative Cotton effect for the
(a) The diastereomer complex pairs resulting from the reaction
(
of 6 with 1-alkynes can be readily separated by standard column
chromatography on silica gel.15
(
b) The enantiomeric excesses obtained in the reactions of
3
the isolated diastereomers with norbornene or norbornadiene,
under tertiary amine N-oxide-mediated conditions, are uniformly
high (93-97%ee) for nonhindered alkynes.
n-π* transition in the CD spectrum. According to the octant
23
rule, this unequivocally establishes an (1R,2R,6S,7S) config-
uration to (-)-24 (Figure 6). Catalytic hydrogenation of (+)-
4 (19% ee) followed by desilylation gave a dextrorotatory
sample of (+)-30. On the other hand, (-)-27 (29% ee) was
2
(19) Intermolecular Pauson-Khand reactions: (a) Bernardes, V.; Ver-
daguer, X.; Kardos, N.; Moyano, A.; Peric a` s, M. A.; Riera, A.; Greene, A.
E. Tetrahedron Lett. 1994, 35, 575-578. (b) Fonquerna, S.; Moyano, A.;
Peric a` s, M. A.; Riera, A. Tetrahedron 1995, 14, 4239-4254. (c) Bernardes,
V.; Kann, N.; Riera, A.; Moyano, A.; Peric a` s, M. A.; Greene, A. E. J. Org.
Chem. 1995, 60, 6670-6671. (d) Fonquerna, S.; Moyano, A.; Peric a` s, M.
A.; Riera, A. J. Am. Chem. Soc. 1997, 119, 10225-10226. (e) Fonquerna,
S.; R ´ı os, R.; Moyano, A.; Peric a` s, M. A.; Riera, A. Eur. J. Org. Chem.
(20) The reaction between complex 2 and norbornadiene has been
reported to give a mixture of the racemic exo- (rac-27) and endo- (rac-28)
adducts: Billington, D. C.; Helps, I. M.; Pauson, P. L.; Thomson, W.;
Willison, D. J. Organomet. Chem. 1988, 354, 233-242.
(21) Under the same reaction conditions, complex 19 decomposed and
gave diphenylacetylene as the sole identifiable product. However, when
the reaction was run under very mild thermal conditions (room temperature,
5 days) an optically active (38% ee) adduct was formed, although in very
low yield.
(22) Montenegro, E.; Moyano, A.; Peric a` s, M. A.; Riera, A.; Alvarez-
Larena, A.; Piniella, J.-F. Tetrahedron: Asymmetry 1999, 10, 457-471.
(23) Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic Compounds;
John Wiley & Sons: New York, 1994; pp 1022-1033.
1
999, 3459-3478. Intramolecular Pauson-Khand reactions: (f) Castro, J.;
S o¨ rensen, H.; Riera, A.; Morin, C.; Moyano, A.; Peric a` s, M. A.; Greene,
A. E. J. Am. Chem. Soc. 1990, 112, 9388-9389. (g) Castro, J.; Moyano,
A.; Peric a` s, M. A.; Riera, A. Tetrahedron: Asymmetry 1994, 5, 307-310.
(
h) Castro, J.; Moyano, A.; Peric a` s, M. A.; Riera, A.; Greene, A. E.; Alvarez-
Larena, A.; Piniella, J. F. J. Org. Chem. 1996, 61, 9016-9020. (i) Tormo,
J.; Moyano, A.; Peric a` s, M. A.; Riera, A. J. Org. Chem. 1997, 62, 4851-
4
856, and refs. cited therein.

Acetylene-Dicobaltcarbonyl Complexes
J. Am. Chem. Soc., Vol. 122, No. 33, 2000 7951
Figure 6. AM1-calculated lowest-energy conformation of compound
(
-)-30 and selected nuclear Overhauser enhancement spectroscopy
correlations (a). Octant rule projection (rear sector) of ketone (-)-30
b).
(
Scheme 8
Figure 7. Enantioselectivity mnemonic for the intermolecular Pauson-
Khand reaction of phosphine-substituted alkyne complexes.
hydrogenated to (-)-30, so that an (1R,2R,6S,7S) configuration
was also assigned to (-)-27.
All in all, these results offer compelling evidence that in
general the levorotatory enantiomers of the Pauson-Khand
enone adducts obtained in this work have the same (2R)
configuration, irrespective of the starting alkyne substituent, and
that therefore the dextrorotatory enantiomers have the opposite
the stereochemical outcome of the reactions of the monodentate,
phosphinooxazoline-substituted complexes can then be explained
by assuming the following: (a) The substitution of a cobalt atom
by a phosphine ligand largely directs the coordination of the
olefin to the unsubstituted cobalt; (b) the olefin (norbornene or
norbornadiene) is bonded to the cobalt by the more accessible
exo-face, and (c) the olefin is oriented in a way that minimizes
the steric interactions of the methylene bridge with the
tetrahedral C2Co2 cluster. In this way, as depicted in Figure 7,
the predominant formation of the (2R) or (2S) products from
the substituted (S)- or (R)-complexes, respectively, can be easily
rationalized. It should furthermore be pointed out that PM3-
(2S) configuration. Most importantly, this conclusion allows us
to establish for the first time a correlation between the absolute
configurations of the chiral phosphine-substituted alkyne com-
plexes and those of the corresponding Pauson-Khand ad-
ducts: In their intermolecular Pauson-Khand reactions either
with norbornene or norbornadiene, 1-alkyne-dicobaltcarbonyl
complexes with mono- or bidentate phosphinooxazoline ligands
coordinated at the pro-S cobalt predominantly afford enones
with a (2R) absolute configuration. ConVersely, the diastereomer
complexes with ligands coordinated at the pro-R cobalt giVe
rise predominantly to the (2S) enantiomers.
16,17
(tm) calculations,
performed on model systems, give support
to this rationalization of the stereochemical outcome of the
reaction (see Supporting Information).
The reduced enantioselectivity shown by the chelated com-
plexes 3 and 5 can also be accommodated within this mecha-
nistic model, assuming that in this case, because of the lability
This enantioselectivity mnemonic rule can be readily ac-
counted for on the basis of the usually accepted mechanism of
the Pauson-Khand reaction, initially proposed by Magnus et
26
of the nitrogen-cobalt bond, coordination of the olefin can
also take place at the substituted cobalt and leads therefore to
the competing formation of both enantiomers of the product.
2
4
14
al. and largely corroborated by subsequent theoretical and
1
1a-c,25
(25) (a) La Belle, B. E.; Knudsen, M. J.; Olmstead, M. M.; Hope, H.;
Yanuck, M. D.; Schore, N. E. J. Org. Chem. 1985, 50, 5215-5222. (b)
Monta n˜ a, A.-M.; Moyano, A.; Peric a` s, M. A.; Serratosa, F. Tetrahedron
experimental
studies. According to this mechanistic
sequence of events, the reaction is initiated by the displacement
of a carbon monoxide from the starting alkyne-dicobaltcarbonyl
complex by the olefin, leading to an intermediate species in
which both the alkyne and the alkene moieties are bonded to
cobalt. Further evolution of this complex (insertion of the
complexed olefin into a carbon-cobalt bond giving a five-
membered cobaltacycle, insertion of carbon monoxide, and
reductive elimination of a dicobaltcarbonyl moiety) leads to the
final cyclopentenone product. Within this mechanistic scheme,
1
985, 41, 5995-6003. (c) Casalnuovo, J. A.; Scott, R. W.; Harwood, E.
A.; Schore, N. E. Tetrahedron Lett. 1994, 35, 1153-1156. (h) Thommen,
M.; Veretenov, A. L.; Guidetti-Grept, R.; Keese, R. HelV. Chim. Acta 1996,
79, 461-476. (d) Corlay, H.; James, I. W.; Fouquet, E.; Schmidt, J.;
Motherwell, W. B. Synlett 1996, 990-993. (e) Kowalczyk, B. A.; Smith,
T. C.; Dauben, W. G. J. Org. Chem. 1998, 63, 1379-1389. (f) Krafft, M.
E.; Wilson, A. M.; Dasse, O. A.; Bonaga, L. V. R.; Cheung, Y. Y.; Fu, Z.;
Shao, B.; Scott, I. L. Tetrahedron Lett. 1998, 39, 5911-5914. (g) Corlay,
H.; Fouquet, E.; Magnier, E.; Motherwell, W. B. Chem. Commun. 1999,
183-184.
(26) PM3(tm) calculations on the relative energies of the chelated and
(
24) (a) Magnus, P.; Exon, C.; Albaugh-Robertson, P. Tetrahedron 1985,
nonchelated forms of complexes 3 and 11a, b indicate that the oxazoline
nitrogen-cobalt bond is ca. 20 kcal mol weaker than a cobalt-carbonyl
one.
-
1
4
2
1, 5861-5869. (b) Magnus, P.; Principe, L. M. Tetrahedron Lett. 1985,
6, 4851-4854.

7952 J. Am. Chem. Soc., Vol. 122, No. 33, 2000
Castro et al.
In summary, the results described in this article exemplify
11b has been X-ray diffracted. Complex 11a: Brown-red crystals; mp
the use of the chiral phosphinooxazoline27 6 as a highly efficient
and practical ligand for the enantioselective intermolecular
Pauson-Khand reactions of 1-alkynes with norbornadiene.
105-106 °C; R 0.24 (hexane:ethyl acetate, 5:1); [R]
25 -968 (c 0.006);
f
D
CD [λmax, nm (∆ꢀ)] 287 (+12.0), 383 (+6.2), 480 (-3.8) (c 8.57 ×
); IR (cm ) 2060, 2010, 1997, 1960, 1655, 1479; H NMR (300
MHz) δ 8.10-8.00 (m, 1H), 7.60-7.45 (m, 2H), 7.43-7.30 (m, 1H),
-
5
-1
1
1
0
7
0
.25-6.60 (m, 16H), 5.54 (d, J ) 3.9 Hz, 1H), 3.80-3.30 (m, 3H),
Experimental Section
Ligands 1, 4, and 610 and complexes 2, 7-10, 16, and 182,28 were
prepared according to standard procedures.
.62 (s, 9H); 13C NMR (75.4 MHz) δ 207.0 (b, CO), 206.0 (b, CO),
202.5 (b, 3CO), 162.6 (C ), 139.8 (C ), 138.0-126.0 (complex signal,
q
q
4C and 19CH), 88.2 (C ), 76.7 (CH), 73.2 (CH), 69.1 (CH ), 34.2
q
q
2
3
1
General Procedure for Preparation of Alkyne-Dicobaltpenta-
carbonyl Complexes Substituted by (-)-[2-[(4S)-4-(tert-Butyl)(1,3-
oxazolin-2-yl)]phenyl]diphenylphosphino 6: Preparation of Com-
plexes 11a,b. To a solution of phenylacetylene-dicobalthexacarbonyl
complex 2 (297 mg, 0.765 mmol) in toluene (10 mL) was added
phosphinooxazoline 6 (210 mg, 0.54 mmol). The dark-red solution was
heated to 60 °C for 2 h 30 min. The reaction mixture was cooled to
room temperature and filtered through Celite, which was thoroughly
washed with methylene chloride. The solvents were eliminated under
reduced pressure, and the dark-brown residue was purified by column
chromatography on silica gel (previously washed with ether and
hexane), eluting with hexanes-ethyl acetate mixtures of increasing
polarity, to afford 155 mg (38%) of 11a and 159 mg (39%) of 11b.
The global yield was 77%. Each diastereomer was recrystallized from
hexane/methylene chloride and then kept in the freezer. One crystal of
(C ), 26.4 (3CH ); P NMR δ +55.23; MS [FAB(+)] m/e ) 748.1
q
+
3
+
+
(M + 1, 1%), 691.1 (M - 2CO, 5%), 663.1 (M - 3CO, 8%), 636.2
+
+
(M - 4CO, 3%), 607.1 (M - 5CO, 60%), 474.1 (20%), 446.1
+
(100%); HRMS (FAB+) calcd for C H Co NOP (M - 4CO)
33
32
2
607.089, found 607.085. Complex 11b: Brown-red crystals; mp 95-
25
96 °C; R 0.10 (hexane:ethyl acetate, 5:1); [R] ) + 637 (c 0.017);
f
D
CD [λ , nm (∆ꢀ)] 342 (+3.03), 392 (-2.4), 492 (+4.4) (c 2.25 ×
max
-
4
-1
1
10 ); IR (cm ) 2060, 2010, 1647, 1593, 1479; H NMR (200 MHz)
δ 7.8-7.5 (m, 5H), 7.2-6.6 (m, 14H), 5.59 (d, J ) 4 Hz, 1H), 3.52-
3.65 (m, 1H), 3.27-3.39 (m, 1H), 2.82-2.98 (m, 1H), 0.69 (s, 9H);
13
C NMR (75.4 MHz) δ 207.6 (b, CO), 206.5 (b, CO), 202.7 (b, 3CO),
163.7 (C ), 139.2 (C ), 138.0-126.0 (complex signal, 4C and 19CH),
90.0 (C ), 75.8 (CH), 72.6 (CH), 69.2 (CH ), 34.4 (C ), 26.4 (3CH );
q
q
q
q
2
q
3
31
+
P NMR δ +58.27; MS [FAB(+)] m/e ) 748.1 (M + 1, 1%), 691.1
+
+
+
(M - 2CO, 7%), 663.2 (M - 3CO, 10%), 607.1 (M - 5CO, 65%),
4
(
74.1 (35%), 446.1 (100%); HRMS (FAB+) calcd for C33
H32Co
2
NOP
(27) For references on the use of chiral phosphinoozaxolines in asym-
+
M - 4CO) 607.089, found 607.085. Conditions for the determination
metric synthesis, see: (a) Von Matt, P.; Pfaltz, A. Angew. Chem., Int. Ed.
Engl. 1993, 32, 566-568. (b) Spinz, J.; Helmchen, G. Tetrahedron Lett.
of the diastereomeric purities of 11a and 11b by HPLC analysis:
1
993, 34, 1769-1772. (c) Dawson, G. J.; Frost, C. G.; Williams, J. M. J.;
CHIRALCEL OD (25 cm) column, 1% 2-propanol 99% hexane, 0.5
Coote, S. J. Tetrahedron Lett. 1993, 34, 3149-3150. (d) Allen, J. V.;
mL/min, 30 °C, λ ) 254 nm, P ) 14 bar. t
1.24 min.
General methods, preparation, and spectroscopic and analytical data
R R
(11a): 9.71 min. t (11b):
Dawson, G. J.; Frost, C. G.; Williams, J. M. J.; Coote, S. J. Tetrahedron
1
1
994, 50, 799-808. (e) Von Matt, P.; Loiseleur, O.; Koch, G.; Pfaltz, A.;
Lefeber, C.; Feucht, T.; Helmchen, G. Tetrahedron: Asymmetry 1994, 5,
of complexes 3, 5, 12a,b-15a,b, 17, and 19, procedures for their
intermolecular Pauson-Khand reactions, and characterization data of
the resulting adducts can be found in the Supporting Information.
5
73-584. (f) Sprinz, J.; Kiefer, M.; Helmchen, G.; Reggelin, M.; Huttner,
G.; Walter, O.; Zsolnai, L. Tetrahedron Lett. 1994, 35, 1523-1526. (g)
Dawson, G. J.; Williams, J. M. J.; Coote, S. J. Tetrahedron Lett. 1995, 36,
4
1
61-462. (h) Lloyd-Jones, G. C.; Pfaltz, A. Angew. Chem., Int. Ed. Engl.
995, 34, 462-464. (i) Jumnah, R.; Williams, A. C.; Williams, J. M. J.
Acknowledgment. Financial support from DGES (PB96-
Synlett 1995, 821-822. (j) Rieck, H.; Helmchen, G. Angew. Chem., Int.
Ed. Engl. 1995, 34, 2687-2689. (k) Loiseleur, O.; Meier, P.; Pfaltz, A.
Angew. Chem., Int. Ed. Engl. 1996, 35, 200-203. (l) Bower, J. F.; Williams,
J. M. J. Synlett 1996, 685-686. (m) Sudo, A.; Saigo, K. J. Org. Chem.
0
376 and PB97-0939) is gratefully acknowledged.
Supporting Information Available: Tables of crystal data,
1
1
997, 62, 5508-5513. (n) Janssen, J. P.; Helmchen, G. Tetrahedron Lett.
997, 38, 8025-8026. (o) Carmona, D.; Cativiela, C.; Elipe, S.; Lahoz, F.
J.; Lamata, M. P.; L o´ pez-Ram de V ´ı u, M. P.; Oro, L. A.; Vega, C.; Viguri,
structure solution and refinement, atomic coordinates, bond
lengths and angles, and anisotropic thermal parameters for 11b.
Evolution of the diastereomeric purity of complexes 11a,b-
F. Chem. Commun. 1997, 2351-2352. (p) Gl a¨ ser, B.; Kunz, H. Synlett
1
2
1
998, 53-54. (q) Sagasser, I.; Helmchen, G. Tetrahedron Lett. 1998, 39,
61-264. (r) Porte, A. M.; Reibenspies, J.; Burgess, K. J. Am. Chem. Soc.
998, 120, 9180-9187. (s) Aeby, A.; Gsponer, A.; Consiglio, G. J. Am.
15a,b in solution. Semiempirical molecular orbital (MO) studies
on phosphinooxazoline-substituted alkyne-dicobaltcarbonyl
complexes. Semiempirical MO studies on the intermolecular
Pauson-Khand reactions of phosphine-substituted alkyne-
dicobaltcarbonyl complexes. Complete Experimental Section
Chem. Soc. 1998, 120, 11000-11001. (t) Flutbacher, D.; Helmchen, G.
Tetrahedron Lett. 1999, 40, 3867-3868. (u) Blacker, A. J.; Clark, M. L.;
Loft, M. S.; Williams, J. M. J. Chem. Commun. 1999, 913-914. (v) Kainz,
S.; Brinkmann, A.; Leitner, W.; Pfaltz, A. J. Am. Chem. Soc. 1999, 121,
(PDF). This material is available free of charge via the Internet
6
421-6429.
(28) (a) Greenfield, H.; Stenberg, R. H.; Friedel, J. H.; Wotiz, R.;
at http://pubs.acs.org.
Manhby, I.; Wender, J. J. Am. Chem. Soc. 1954, 76, 1457-1458. (b)
Lockwood, R. F.; Nicholas, K. M. Tetrahedron Lett. 1977, 4163-4166.
JA001143O