A new chiral bidentate (P,S) ligand for the asymmetric intermolecular Pauson - Khand reaction [19]

Full text of DOI:10.1021/ja001839h

10242
J. Am. Chem. Soc. 2000, 122, 10242-10243
Chart 1a
A New Chiral Bidentate (P,S) Ligand for the
Asymmetric Intermolecular Pauson-Khand Reaction
§
§
,§
Xavier Verdaguer, Albert Moyano, Miquel A. Peric a` s,*
,§
†
†
Antoni Riera,* Miguel Angel Maestro, and Jos e´ Mah ´ı a
Unitat de Recerca en S ´ı ntesi Asim e` trica
Departament de Qu ´ı mica Org a` nica, UniVersitat de
Barcelona, Mart ´ı i Franqu e` s, 1-11, 08028 Barcelona, Spain
SerVicios Xerais de Apoio a´ InVestigaci o´ n
a
CO ligands are omitted for clarity.
Campus Zapateria, s/n, UniVersidade da Coru n˜ a
Scheme 1
1
5071, A Coru n˜ a, Spain
ReceiVed May 30, 2000
In the past two decades the Pauson-Khand reaction (PKR)1
has attracted much attention from the synthetic chemistry com-
munity. Although some progress has been achieved lately on the
way to convert the intramolecular PKR into a catalytic enantio-
2
selective process, the intermolecular version of the process has
been left out from most of these advances.3 To turn the
intermolecular PKR into an asymmetric transformation, the use
diastereoselectivity of its formation. The most important step in
the design of such a chiral bidentate ligand was to drive the
coordination of the sulfur in the dicobalt-alkyne cluster to the
cobalt atom not bonded to phosphorus. To obtain such a
coordination pattern, the distance between the P and S atoms
becomes crucial. A methylene link between the sulfide and the
phosphine11 could provide an excellent scaffold for this purpose.
Since no chiral ligands bearing S and P in such close proximity
could be found in the literature, we chose oxathiane 1, which is
readily accessible from natural (+)-pulegone,12 as the starting
material for our synthesis. Chlorodiphenylphosphine was first
alkylated with the lithium anion of 1, generated at low temperature
by treatment with s-BuLi (Scheme 1). The reaction was totally
stereoselective, affording the chiral phosphine 2 (PuPHOS) as a
single diastereomer. The new phosphine was most conveniently
isolated in its borane-protected form 3 as a shelf-stable, highly
crystalline solid in 81% overall yield. The stereochemistry of the
newly formed center was assumed to be the one depicted in
Scheme 1, with the phosphorus substituent equatorial at C-2 of
the oxathiane ring.
4,5,6
of covalently bonded chiral auxiliaries,
chiral ligands on
cobalt,7 and chiral promoters has been explored. The use of
chiral auxiliaries has been extensively investigated by our group,5
and we have introduced the extremely efficient inductors I (Chart
,8
9
,6
1), bearing a sulfide arm that is able to coordinate to the cobalt
complex of the alkynyl derivatives as in structure II, thus
enhancing both the reactivity and stereoselectivity of the inter-
molecular PKR.6
,10
Several phosphines have been used as chiral ligands on cobalt;
however, many drawbacks hamper this methodology, i.e., low
diastereoselectivity in the formation of type III complexes,
cumbersome separation of these diastereomeric mixtures, and
decreased reactivity toward the PKR.
We reasoned that a bidentate ligand, designed to form chelated
structures such as IV, would increase, as for the covalently bonded
chiral auxiliaries, both the reactivity of the complex and the
§
Universitat de Barcelona.
†
Universidade da Coru n˜ a.
(
1) (a) Buchwald, S. L.; Hicks, F. A. In Pauson Khand Type Reactions;
Jacobsen, E. N., Pfaltz, A., and Yamamoto, H., Eds.; Springer: Berlin, 1999;
The free PuPHOS ligand (2) was conveniently generated in
situ by simply heating in toluene the mixture of 3 with 2 equiv
of 1,4-diazabicyclo[2.2.2]octane (DABCO). Generation of 2 in
the presence of dicobalt hexacarbonyl complexes 4 derived from
terminal alkynes smoothly led to a diastereomeric mixture of
dicobalt tetracarbonyl complexes 5/6. TLC monitoring showed
that at the initial stages of the reaction both diastereomers were
in an almost 1/1 ratio, as was the case with the previously
described nonchelated phosphines.7 Fortunately, and accord-
ing to our expectations, heating the solution for 17-18 h at
Vol. II, pp 491-510. (b) Chung, Y. K. Coord. Chem. ReV. 1999, 188, 297-
3
9
41. (c) Geis, O.; Schmalz, H. G. Angew. Chem., Int. Ed. Engl. 1998, 37,
11-914. (d) Schore, N. E. Org. React. (N.Y.) 1991, 40, 1-90.
(
2) (a) Hicks, F. A.; Buchwald, S. L. J. Am. Chem. Soc. 1999, 121, 7026-
7
2
033. (b) Hiroi, K.; Watanabe, T.; Kawagishi, R.; Abe, I. Tetrahedron Lett.
000, 41, 891-895. (c) Hiroi, K.; Watanabe, T.; Kawagishi, R.; Abe, I.
Tetrahedron: Asymmetry 2000, 11, 797-808.
(
3) The unsuccessful use of chiral phosphines in catalytic intermolecular
PKR is described in ref 2c.
4) Recent examples: (a)Witulski, B.; Gossmann, M. Chem. Commun.
(
,8
1
1
3
999, 21, 1879-1880. (b) Adrio, J.; Carretero, J. C. J. Am. Chem. Soc. 1999,
21, 7411-7412. (c) Hiroi, K.; Watanabe, T. Tetrahedron Lett. 2000, 41,
935.
60-80 °C induced the equilibration of the diastereomers, leading
(
5) (a) Balsells, J.; Moyano, A.; Riera, A.; Peric a` s, M. A. Org. Lett. 1999,
to biased mixtures of complexes in excellent yields (Table 1).
The observed stereoselectivity for this process mostly depended
on the nature of the substituent on the alkyne. While for R ) Ph
no diastereoselectivity at all was detected in the complexation
process (entry 1, Table 1), when the reaction was carried out with
the dicobalt complexes derived from tert-butylacetylene and
trimethylsilylacetylene, the stereoselectivity increased to 3/1
(entries 2 and 3, Table 1). The higher selectivity level in the
complexation process (dr ) 4.5/1) was reached when the complex
of 2-methyl-3-butyn-2-ol was employed (entry 4, Table 1).
Whereas diastereomers 5a/6a could be separated by column
1
, 1981-1984. (b) Fonquerna, S.; Rios, R.; Moyano, A.; Peric a` s, M. A.; Riera,
A. Eur. J. Org. Chem. 1999, 3459-3478 and references therein.
(
6) (a) Verdaguer, X.; Vazquez, J.; Fuster, G.; Bernardes-Genisson, V.;
Greene, A. E.; Moyano, A.; Peric a` s, M. A.; Riera, A. J. Org. Chem. 1998,
3, 7037-7052. (b) Montenegro, E.; Poch, M.; Moyano, A.; Peric a` s, M. A.;
Riera, A. Tetrahedron Lett. 1998, 39, 335-338.
7) (a) Brunner, H.; Niedernhuber, A. Tetrahedron: Asymmetry 1990, 1,
6
(
7
11-714. (b) Park, H.-J.; Lee, B. Y.; Kang, Y. K.; Chung, Y. K. Organo-
metallics 1995, 14, 3104-3107. (c) Gimbert, Y.; Robert, F.; Durif, A.;
Averbuch, M. T.; Kann, N.; Greene, A. E. J. Org. Chem. 1999, 64, 3492-
3
497. (d) Hay, A. M.; Kerr, W. J.; Kirk, G. G.; Middlemiss, D. Organome-
tallics 1995, 14, 4986-4988.
8) Castro, J.; Moyano, A.; Peric a` s, M. A.; Riera, A.; Alvarez-Larena, A.;
Piniella, J. F. J. Am. Chem. Soc. 2000, 122, 7944-7952.
9) Kerr, W. J.; Lindsay, D, M.; Rankin, E. M. Scott, J. S.; Watson, S. P.
Tetrahedron Lett. 2000, 41, 3229-3233.
(
(
(11) Edwards, A. J.; Mack, S. R.; Mays, M. J.; Mo, C. Y.; Raithby, P. R.;
Rennie, M. A. J. Organomet. Chem. 1996, 519, 243-252.
(12) Eliel, E. L.; Lynch, J. E.; Kume, F.; Frye, S. V. Org. Synth. 1987, 65,
215-223.
(
10) Sulfur coordination to cobalt was first introduced to control the
regioselectivity of the PKR. Kraft, M. E.; Juliano, C. A.; Scott, I. L.; Wright,
C.; McEachin, M. D. J. Am. Chem. Soc. 1991, 113, 1693-1703.
1
0.1021/ja001839h CCC: $19.00 © 2000 American Chemical Society
Published on Web 09/30/2000

Communications to the Editor
J. Am. Chem. Soc., Vol. 122, No. 41, 2000 10243
Table 1. Thermal Reaction of PuPHOS with Alkyne-Dicobalt
Hexacarbonyl Complexes
Table 2. Pauson-Khand Reaction of PuPHOS Complexes with
Norbornadiene
yield
starting
complex (°C) (h)
4ab
4b
4c
T
time yield
conditionsa
(%) eeb product
complex
R
time
entry
R
(%)
dra
1/1
3/1
3/1
product
5a
5c
5c
6c
5d
Ph
toluene/50 °C
toluene/50 °C
30 min 99 99 (+)-7a
1
2
3
4
Ph
Bu
TMS
CMe
65
60
80
70
18
17
17
17
91
98
91
84
5a/6a
5b/6b
5c/6c
TMS
TMS
TMS
3 d
92 57 (+)-7c
93 97 (+)-7c
94 95 (-)-7c
98 70 (+)-7d
t
CH
CH
OH CH
2
2
2
Cl
Cl
Cl
2
/NMO/rt 3 d
2
/NMO/rt 3 d
2
/NMO/rt 4 d
2
OH
4d
4.5/1 5d/6d
CMe
2
a
1
Established by H NMR spectroscopy of the resulting mixture of
a
All reactions were conducted in Schlenk flasks under nitrogen with
0 equiv of norbornadiene. b Enantiomeric excess (%) was determined
either by HPLC (Chiracel-OD, 7a and 7d) or by GC (â-DEX, 7c).
b
2 8
complexes. Starting complex 4a was prepared in situ (Co (CO) /
phenylacetylene/toluene) prior to ligand addition.
1
stereoselectivity (57% ee). Most gratifyingly, we could improve
this result by employing N-methylmorpholine N-oxide (NMO)
in CH Cl at room temperature. Under these conditions, 5c reacted
2 2
at a similar rate but with increased selectivity (97% ee). In a
similar fashion, the minor isomer 6c yields the enantiomeric
cyclopentenone (-)-7c, in both high yield and high enantiomeric
excess (95%).
These results are in good agreement with the hypothesis that
the sulfide moiety exerts a dual effect in the reaction process.
The thioether being the more labile of the two coordinative bonds
(Co-S/Co-P), its dissociation controls the stereochemistry of
the reaction while leaving, on a precise cobalt atom, a free
coordination site for the incoming alkene. Moreover, since
dissociation of a hemilabile sulfide moiety is much easier than
the loss of any CO ligand in the complex, the normally difficult
dissociative step in the PKR is facilitated and the overall rate
Figure 1. ORTEP plot of complex 5d.
chromatography, the major diastereomers 5b, 5c, and 5d were
isolated by simple crystallization. This allowed for a convenient
preparative-scale isolation of diastereomerically pure material. On
top of that, additional isomerization of the mother liquor back to
the original diastereomeric mixture could provide a second crop
of crystals, affording an increased yield of the major crystalline
compound. For example, in the case of complex 4c, after a
sequence of crystallization-isomerization-crystallization, a 68%
yield of diastereomerically pure complex 5c was obtained.
X-ray analysis of 5d (Figure 1) confirmed the stereochemistry
of the diphenylphosphino substituent in the ligand and showed
that the sulfur and the phosphorus atoms were occupying two
eclipsed pseudoequatorial coordination sites at different metal
centers, anti to the dimethylcarbinol group, to avoid steric
interactions.7 Moreover, the sulfur atom was coordinated to the
pro-S cobalt atom through its equatorial electron lone pair.
It is well known that mono- and diphosphino dicobalt com-
plexes (III) of phenylacetylene display lower reactivity in the
PKR. In sharp contrast with this, when the PuPHOS-phenyl-
acetylene complex 5a was reacted thermally with norbornadiene,
the PKR took place in an extremely rapid and stereoselective
fashion (Table 2). Within 30 min at 50 °C, the corresponding
15
increased. The role of NMO in these processes is intriguing
since it does not have a significant effect on the reaction rate but
clearly increases the stereoselectivity. We have observed in related
compounds that CO promotes complex epimerization, probably
through the intermediacy of nonchelated species. Accordingly,
NMO probably operates by preventing the presence of any free
CO in the reaction medium.
In conclusion, we have prepared the new phosphine PuPHOS
(2) and demonstrated its utility in the asymmetric Pauson-Khand
reaction. PuPHOS illustrates an unprecedented multiple effect:
a significant diastereoselectivity in its coordination to the prochiral
dicobalt complex by thermodynamic equilibration, an increased
reactivity with respect to normal phosphine-coordinated alkyne-
dicobalt complexes, and efficient stereocontrol by directing the
reaction to the cobalt atom where sulfur is coordinated.
c
Acknowledgment. Financial support from DGICYT (PB98-1246) and
CIRIT (1998SGR-00005) is gratefully acknowledged. X.V. thanks the
MEC for a fellowship.
Supporting Information Available: Tables of complete X-ray crystal
data, ORTEP drawings, refinement parameters, atomic coordinates, and
bond distances and angles for 5d (PDF). This material is available free
of charge via the Internet at http://pubs.acs.org.
13
cyclopentenone (+)-7a was obtained in almost quantitative yield
and 99% ee. Complex 5b revealed a marked decrease in reactivity
compared to its phenyl analogue 5a and did not afford the
corresponding adduct. Alternatively, complexes 5c and 5d
provided the corresponding Pauson-Khand adducts in excellent
yields. Thermal cycloaddition of 5c at 30 °C for 3 days produced
the corresponding adduct (+)-7c8 in high yield but moderate
JA001839H
(
14) Mukai, C.; Uchiyama, M.; Hanaoka, M. Chem. Commun. 1992, 1014-
,14
1015.
(
15) (a) Jeong, N.; Chung, Y. K.; Lee, B. Y.; Lee, S. H.; Yoo, S. E. Synlett
(
13) Montenegro, E.; Moyano, A.; Peric a` s, M. A.; Riera, A.; Alvarez-
1991, 204-206. (b) Shambayati, S.; Crowe, W. E.; Schreiber, S. L.
Larena, A.; Piniella, J. E. Tetrahedron: Asymmetry 1999, 10, 457-471.
Tetrahedron Lett. 1990, 31, 5289-5292.