Tandem Aminocarbonylation/ Pauson-Khand Reaction of Haloacetylenes

Article abstract of DOI:10.1021/ol991145h

(Matrix Presented) The dicobalt hexacarbonyl complex of 1-chloro-2-phenylacetylene decomposes in solution at room temperature affording similar amounts of two new complexes, to which the structures of a dichloro tetracobalt decacarbonyl complex of 1,4-diphenyl-1,3-butadiyne and of a 1-chloro-2-phenylacetylene acylcobalt complex have been tentatively assigned. The acyl complex can be efficiently trapped by amines, and the resulting aminocarbonylation products submitted to Pauson-Khand reaction to yield cyclopentenones with the regiocontrolled formation of five new bonds in a single synthetic operation.

Full text of DOI:10.1021/ol991145h

ORGANIC
LETTERS
1
999
Vol. 1, No. 12
981-1984
Tandem Aminocarbonylation/
Pauson-Khand Reaction of
Haloacetylenes
1
Jaume Balsells, Albert Moyano, Antoni Riera, and Miquel A. Peric a` s*
Unitat de Recerca en S ´ı ntesi Asim e` trica, Departament de Qu ´ı mica Org a` nica,
UniVersitat de Barcelona, c/ Mart ´ı i Franqu e` s, 1-11, E-08028 Barcelona, Spain
mpb@ursa.qo.ub.es
Received October 13, 1999
ABSTRACT
The dicobalt hexacarbonyl complex of 1-chloro-2-phenylacetylene decomposes in solution at room temperature affording similar amounts of
two new complexes, to which the structures of a dichloro tetracobalt decacarbonyl complex of 1,4-diphenyl-1,3-butadiyne and of a 1-chloro-
2-phenylacetylene acylcobalt complex have been tentatively assigned. The acyl complex can be efficiently trapped by amines, and the resulting
aminocarbonylation products submitted to Pauson−Khand reaction to yield cyclopentenones with the regiocontrolled formation of five new
bonds in a single synthetic operation.
Organometallic processes nowadays enjoy a prominent
position in synthetic organic chemistry. In particular, the
possibility of achieving intricate structures by forming several
bonds in a single synthetic step has made this chemistry
especially attractive. In this context, the chemistry of
hexacarbonyldicobalt complexes of acetylenes has elicited
considerable attention. Besides their use in the stabilization
of propargyl cations (Nicholas reaction),1 they can be
convergently assembled with alkenes to give cyclopenten-
ones, in the process commonly known as the Pauson-Khand
starting materials. Among chiral acetylenic substrates, the
3
4
use of alkoxyacetylenes, alkylthioacetylenes, alkynyl sul-
5
6
foxides, and 2-alkynoate derivatives has been successfully
exploited for this purpose. As a continuation of these efforts,
and bearing in mind the development of a catalytic enanti-
oselective version of the Pauson-Khand cycloaddition, the
unprecedented use of the labile haloacetylenes as substrates
for this process was planned, but the course of these studies
has evolved into the discovery of a new reaction. Herein we
report on how the dicobalt hexacarbonyl complexes of
haloacetylenes thermally evolve into new, presumably acyl-
cobalt complexes which can be trapped by amines to form
hexacarbonyldicobalt complexes of propynoyl amides, and
how this aminocarbonylation process can be coupled in a
tandem manner with both inter- and intramolecular Pauson-
Khand reactions, with the formation of five bonds in a single
synthetic operation. Moreover, the aminocarbonylation pro-
cess can be combined with previously developed methodol-
2
reaction (PKR). Over the past few years, much of our
research effort has been focused on the development of
efficient asymmetric versions of this useful reaction based
on the use of chiral auxiliaries covalently bonded to the
(1) For leading references, see: (a) Caffyn, A. J. M.; Nicholas, K. M. In
ComprehensiVe Organometallic Chemistry II; Hegedus, L. S., Ed.; Elsevi-
er: Oxford, 1995; Vol. 12, pp 685-702. (b) Nicholas, K. M. Acc. Chem.
Res. 1987, 20, 207-214.
(
2) For recent reviews, see: (a) Chung, Y. K. Coord. Chem. ReV. 1999,
1
88, 297-341. (b) Schore, N. E. In ComprehensiVe Organometallic
Chemistry II; Hegedus, L. S. Ed.; Elsevier: Oxford, 1995; Vol. 12, pp 703-
39.
3) Verdaguer, X.; V a´ zquez, J.; Fuster, G.; Bernardes-G e´ nisson, V.;
Greene, A. E.; Peric a` s, M. A.; Riera, A. J. Org. Chem. 1998, 63, 7037-
052 and references therein.
(4) Montenegro, E.; Poch, M.; Moyano, A.; Peric a` s, M. A.; Riera, A.
Tetrahedron Lett. 1998, 39, 335-338 and references therein.
(5) Montenegro, E.; Moyano, A.; Peric a` s, M. A.; Riera, A.; Alvarez-
Larena, A.; Piniella, J. F. Tetrahedron: Asymmetry 1999, 10, 457-471.
(6) Fonquerna, S.; Moyano, A.; Peric a` s, M. A.; Riera, A. J. Am. Chem.
Soc. 1997, 119, 10225-10226 and references therein.
7
(
7
1
0.1021/ol991145h CCC: $18.00 © 1999 American Chemical Society
Published on Web 11/17/1999

ogy for stereocontrol in intermolecular Pauson-Khand
reaction for the completely diastereoselective synthesis of
cyclopentenone derivatives.
At the outset of this research, we studied the Pauson-
Khand reaction of 1-chloro-2-phenylacetylene 1 with nor-
bornadiene (Scheme 1). The formation of the dicobalt
spectroscopic data with an authentic sample. Finally, the
presence of two chorine atoms in its structure was confirmed
by elemental analysis. If the composition shown in Scheme
1 is assumed, the amount of 4 formed in the reaction accounts
for a 55% of the initial 1 in a highly reproducible manner.
Complex 4 shows good stability under a CO atmosphere and
does not revert to 2 nor interconvert with 5 on heating.11
Complex 5, in turn, is a polar, very labile compound which
could not be isolated. From a structural point of view, 5
Scheme 1. Thermal Behavior of the Dicobalt Hexacarbonyl
Complex of 1-chloro-2-phenylacetylene (2)
-1 12
appears to be an acylcobalt complex (ν ) 1763 cm ), and
in fact, it can very efficiently be trapped by nitrogen
nucleophiles to afford the amide complexes 6 (see below).13
We have established by independent synthesis and reactivity
analysis that 5 is not the dicobalt hexacarbonyl complex of
14
phenylpropynoyl chloride. Somewhat surprisingly, 5 reacts
with NBD at 60 °C to afford cyclopentenone 315 in 45%
yield (from 1). It is interesting to note that this process and
the one leading to 6 involve carbonylation at the two different
carbons of the triple bond in 1. Although the yield for the
formation of 5 cannot be directly measured, an estimated
value of 45% ensures the balance of matter from 1 (combined
yield of 4 and 5 is 100%) and fully accounts for the isolated
yields of 3 and 6 (see below).
Our tentative structural proposal for 5, being compatible
with the experimental observations reported here, also
appears to be viable from an energetic point of view as
1
6
17
indicated by single-point DFT calculations on PM3(tm) -
optimized geometries of a model system (Figure 1).
hexacarbonyl complex 2 took place uneventfully at 0 °C,
and treatment of this complex with norbornadiene (NBD)
7
and N-methylmorpholine N-oxide (NMO) at that tempera-
ture afforded the expected â-chlorocyclopentenone 3 in 12%
yield. This is, in fact, the first example of the PKR of an
8
haloacetylene. However, when the thermally promoted
reaction was attempted, an abnormal behavior of complex 2
was observed. When the reaction mixture was warmed to
room temperature, complex 2 quickly disappeared and similar
amounts of two new complexes, 4 (apolar) and 5 (highly
polar), were formed. We subsequently found that the
decomposition of 2 takes place readily in toluene without
the need for any added reagent and that, for synthetic
purposes, this mixture of complexes can be directly prepared
at room temperature.
Figure 1. Model DFT studies on the formation of 5.
The reaction of 5 with amines leading to 6 is of
A tentative structural assignment of 4 and 5 is based on
the following experimental observations.
Complex 4 was readily isolated by column chromatogra-
considerable interest. Whereas examples of reductive meth-
3
18
oxycarbonylation and aminocarbonylation with concomi-
tant deprotection of alkyne cobalt complexes under forcing
conditions are known, the present sequence is the first
phy (SiO
presence of a PhCtCCtCPh‚Co
18). The proposed structure of the organic ligand was
2
, hexanes), and FAB(+) analysis suggested the
4
(CO)10 moiety (m/e )
7
(
10) (a) H u¨ bel, W.; Mer e´ nyi, R. Chem. Ber. 1963, 96, 930-943. (b)
Dickson, R. S.; Tailby, G. R. Aust. J. Chem. 1969, 22, 1143-1148.
11) Attempts to grow a single crystal from solutions of 4 have failed.
Work aimed to the preparation of a crystalline analogue is actively pursued.
12) For IR spectra of acylmetal complexes, see, for instance: van Asselt,
9
confirmed by oxidative decomplexation with NMO, which
yielded 1,4-diphenyl-1,3-butadiyne in 42% yield. That 4 is
not the tetracobalt dodecacarbonyl complex of 1,4-diphenyl-
(
(
1
0
R.; Gielens, E. C. G.; R u¨ lke, R. E.; Vrieze, K.; Elsevier: C. J. J. Am. Chem.
1
,3-butadiyne was readily established by comparison of
Soc. 1994, 116, 977-985.
1
(
13) All new compounds were fully characterized by H and 13C NMR,
(
7) Shambayati, S.; Crowe, W. E.; Schreiber, S. L. Tetrahedron Lett.
990, 31, 5289-5292.
8) The regiochemical assignment of 3 is based both on the universally
observed regiochemical preferences of phenyl substituted acetylenes in PKR
IR, MS, and HRMS.
1
(14) An authentic sample of this complex, prepared from phenylpropy-
noyl chloride and octacarbonyl dicobalt exhibited a distinct IR spectrum
and did not react with NBD to afford 3.
(15) In could be established that 4, isolated by column chromatography,
does not react with NBD at that temperature to yield any cyclopentenone
adduct.
(
1
3
and on C chemical shift correlations.
9) Krafft, M. E.; Scott, I. L.; Romero, R. H.; Feibelmann, S.; Van Pelt,
C. E. J. Am. Chem. Soc. 1993, 115, 7199-7207.
(
1982
Org. Lett., Vol. 1, No. 12, 1999

example of aminocarbonylation of an alkyne dicobalt hexac-
arbonyl complex.19 Some examples of the aminocarbonyla-
tion reaction have been summarized in Table 1. The reaction
the reaction. Somewhat surprisingly, the presence/absence
of a CO atmosphere has no effect on the course and yield of
the reaction.
With complexes 6a-c in hand, their Pauson-Khand
reactivity was explored (Table 1). By working with the
isolated complexes, the reaction with NBD took place in
almost quantitative yield and, in the case of 6c, with complete
Table 1. Tandem Aminocarbonylation/Pauson-Khand
Reactions
6
diastereocontrol. Quite interestingly, the carbonylation and
Pauson-Khand reaction could be performed in a tandem
manner as a one-pot procedure without decrease in yield or
diastereoselectivity. In this way, five new bonds can be
created in a single process from complex 5 with excellent
yield and, in some cases, complete stereocontrol.
In view of these results, we reasoned that the use of
allylamines in the aminocarbonylation process, in combina-
tion with a subsequent intramolecular Pauson-Khand reac-
tion, could allow the easy assembly of nitrogen containing
polycyclic systems. Results in this direction are summarized
in Table 2.
Table 2. Assembly of Azadi- and Azatriquinanes by Tandem
Aminocarbonylation/Pauson-Khand Reaction
a
From 5. b From isolated 6a-c.
takes place in very high yield with both primary and
secondary amines (entries a and b). With less nucleophilic
nitrogen species, like Oppolzer’s 10,2-camphorsultam, the
aminocarbonylation does not take place. However, it can be
induced by the use of the corresponding lithium amide (entry
c).
Experiments aimed at determining the effect of substituents
of the starting alkyne on the aminocarbonylation process have
been performed. With respect to the halogen atom, the use
of bromoalkynes instead of chloroalkynes leads to highly
decreased yields of amide complexes (28 vs 100% for 6a).
As for the other substituent of the triple bond, electron-
donating groups (RS-, R
3
Si-) stabilize the initial complex
2, preventing the formation of the putative acylcobalt
intermediate 5. Probably in connection with this, the ami-
nocarbonylation of 1-alkoxy-2-chloroacetylenes occurs in
slightly diminished yields. On the other hand, 1-chloro-2-
alkylacetylenes are also convenient substrates for the reaction.
From an experimental point of view, the reaction is
performed by treating a mixture of complexes 4 and 5,
generated from 1, with a slight excess (relative to 5) of amine
a
From 5. b A: 4 h, 45 °C. B: NMO, 20 min, 0 °C. c Yields are based
on isolated 8. Values in parentheses are yields for one-pot reaction.
or lithium amide (1.07-1.33 equiv) and K
2
CO
3
(2.2 equiv)
As can be seen, the interesting 3-azabicyclo[3.3.0]oct-1(8)-
2
1
in toluene, the process being complete after 5 min at room
temperature. Simple column chromatography allows recovery
of the unreacted complex 4 and the isolation of the new
ene-2,7-dione system is readily constructed through the
tandem process. Also in this case, the aminocarbonylation
and Pauson-Khand reactions can be performed in a one-
pot manner without decrease in the efficiency of the process.
The use of a chiral allylamine (entries b and c) allows for a
certain degree of stereochemical control; however, given the
complex 6.20 The use of soluble bases instead of K
CO
O, 80%;
3
CN, 0% 6a) has a deleterious effect on
2
3
(
Hunig’s base, 48% 6a) or more polar solvents (Et
2
CH Cl , 44%; CH
2
2
Org. Lett., Vol. 1, No. 12, 1999
1983

distance between the auxiliaries and the newly created
stereogenic center, more discriminating agents would be
required for achieving practical diastereoselectivities. As a
further demonstration of the synthetic potential of this
methodology, the straightforward and high-yield construction
of the angular triquinane system through the simple use of
a cyclic allylamine is illustrated in entry c.
In summary, the aminocarbonylation plus Pauson-Khand
reaction of chloroacetylenes, which involves the regiocon-
trolled formation of five new bonds in a single synthetic
operation, allows the immediate assembly of a variety of
polycyclic structures from readily available precursors. The
process may be amenable to complete stereocontrol by the
use of Oppolzer’s 10,2-camphorsultam, opening a new route
to enantiopure cyclopentenone systems and, due to the
diverse availability of synthetic precursors (chloroacetylenes
and amines) and easy operation, it holds promise as an
efficient method for the preparation of libraries of cylopen-
tenone products through parallel synthesis in solution.
Extension and application of this methodology, as well as
structural and mechanistic studies on the intermediate
complexes 4 and 5 are underway in our laboratories.
(16) The calculations were performed with the ADF 2.0.1 code, with
the II(DZ) small core basis set, using the VWN local exchange correlation
potential with Perdew-Wang 91 exchange and correlation corrections: (a)
Baerends, E. J.; Ellis, D. E.; Ros, P. E. Chem. Phys. 1973, 2, 41-51. (b)
Versluis, L.; Ziegler, T. J. Chem. Phys. 1988, 88, 322-328. (c) Fan, L.;
Ziegler, T. J. Chem. Phys. 1991, 95, 7401-7408. (d) teVelde, G.; Baerends,
E. J. J. Comput. Phys. 1992, 99, 84-98.
(
17) SPARTAN, version 4.1.1, Wavefunction, Inc., 18401 Von Karman
Ave., Suite 370, Irvine, CA 92612.
18) Sugihara, T.; Okada, Y.; Yamaguchi, M.; Nishizawa, M. Synlett
999, 768-770.
19) For the aminocarbonylation of CpW(CO)3 prop-2-ynyl complexes,
see: Shiu, L. H.; Wang, S.-L.; Wu, M.-J.; Liu, R.-S. Chem. Commun. 1997,
055-2056.
20) When these conditions are applied to complex 4 alone, no
aminocarbonylation is observed at all.
21) The 3-azabicyclo[3.3.0]octan-7-one system has been used as a
precursor to R-kainic acid (Yoo, S.; Lee, S. H. J. Org. Chem. 1994, 59,
968-6972) and to serotonergic agents (Becker, D. P.; Flynn, D. L.
Tetrahedron 1993, 49, 5047-5054).
(
1
(
Acknowledgment. We thank DGICYT (PB95-0265) and
CIRIT (1998SGR-00005) for financial support. J.B. thanks
CIRIT for a fellowship. We also thank Mr. Jordi V a` zquez
for technical assistance in performing the DFT calculations
2
(
(
6
OL991145H
1984
Org. Lett., Vol. 1, No. 12, 1999