Key process in palladium-catalyzed asymmetric transformation of propargyl electrophiles. Racemization of optically active η1-allenylpalladium(II) [3]

Full text of DOI:10.1021/ja010583s

7164
J. Am. Chem. Soc. 2001, 123, 7164-7165
Key Process in Palladium-Catalyzed Asymmetric
Transformation of Propargyl Electrophiles.
Racemization of Optically Active
η1-Allenylpalladium(II)
Sensuke Ogoshi,* Takuma Nishida, Tsutomu Shinagawa, and
Hideo Kurosawa*
Department of Applied Chemistry, Faculty of Engineering
Osaka UniVersity, Suita, Osaka 565-0871, Japan
ReceiVed March 5, 2001
Transition metal-catalyzed asymmetric reactions are a very
powerful tool for organic synthesis, where either configurational
rigidity or flexibility of the organometal intermediate is often a
very crucial issue for the attainment of a highly selective outcome
depending on the reaction type. For instance, in palladium-
catalyzed reactions of propargyl or allenyl electrophiles, quite
rapid interconversion between the enantiomers of allenyl complex
having a chiral axis1 is necessary for the dynamic kinetic
resolution reaction of racemic propargyl substrates,2 while the
enantiomeric stability must be high enough to avoid partial
racemization of optically active propargyl substrates.3 Here we
report novel racemization of the optically active mononuclear η1-
allenylpalladium complex, a conventional intermediate in catalytic
cycles, by way of the exchange of its allenyl ligand with that in
the highly configurationally labile µ-η3-allenyl/propargyldipalla-
dium complex, a process that could occur easily under usual
catalytic reaction conditions.
Figure 1. Racemization of 1a at 25 °C: (3) C6D6 solution prepared
under air; (×) C6D6 solution prepared under N2; (+) CHCl3 solution
prepared under N2; (4) in the presence of 10 mol % of 2a. CHCl3 solution
prepared under N2.
Scheme 1
Scheme 2
Optically active allenylpalladium complexes (1a-c) were
prepared from the reaction of the corresponding optically active
propargyl chlorides with Pd2(dba)3 and PPh3 and the optical
rotation of a solution of 1 was large enough to allow us to follow
the racemization by measurement of its decrease (eq 1).4,6
catalytic manner, than in the oxygen-free solution (Figure 1).7
These results suggest that the presence of oxygen in the solution
of 1a or 1b having â-hydrogen leads to generation of a catalyst
or mediator responsible for the racemization. The 1H and 31P NMR
spectra of the residue recovered after the racemization experiment
with 1a in the C6H6 solution prepared under air showed the
presence of 1a (87%), OdPPh3 (7.6%), 1-phenyl-4-buten-1-yne
(6.8%), and the µ-η3-allenyl/propargyl dinuclear complex (2a: R
) CH3, Scheme 1) (6.2%).
A possible path for generation of 2a and the other minor
products in the presence of oxygen is depicted in Scheme 2. First,
the â-hydrogen elimination may take place in a propargyl isomer,
which is assumed to lie in equilibrium with 1a,8 to give enyne
and HPdCl(PPh3)2 and subsequently “Pd(PPh3)2” species. Then
this may react with oxygen to give OdPPh3 and PPh3-deficient
Pd(0) species, the latter of which might react further with 1a to
give 2a.9 The addition of 10 mol % of PPh3 to a solution of 1a
prepared even under air suppressed the racemization of 1a
Although very slow racemization of 1a and 1b was observed in
a solution of oxygen-free C6H6 or CHCl3, 1c having no â-hy-
drogen was totally stable with respect to the racemization under
the same conditions. The racemization of 1a in a solution prepared
under air proceeded considerably faster, somewhat in an auto-
(1) No chiral propargyl complex has been known, since the introduction
of substituents on the propagylic carbon leads to the formation of allenyl
complexes exclusively.
(2) Mikami, K.; Yoshida, A. Angew. Chem., Int. Ed. Engl. 1997, 36, 858.
(3) Elsevier, C. J.; Stehouwer, P. M.; Westmijze, H.; Vermeer, P. J. Org.
Chem. 1983, 48, 1103. Elsevier, C. J.; Mooiweer, H. H.; Kleijn, H.; Vermeer,
P. Tetrahedron Lett. 1984, 25, 5571. Elsevier, C. J.; Vermeer, P. J. Org. Chem.
1985, 50, 3042. Dixneuf, P.; Guyot, T.; Ness, M. D.; Roberts, S. M. J. Chem.
Soc., Chem. Commun. 1997, 2083. Marshall, J. A.; Wolf, M. A.; Wallace, E.
M. J. Org. Chem. 1997, 62, 367. Marshall, J. A.; Adams, N. D. J. Org. Chem.
1998, 63, 3812. Marshall, J. A.; Grant, C. A. J. Org. Chem. 1999, 64, 696.
Konno, T.; Tanikawa, M.; Ishihara, T.; Yamanaka, H. Chem. Lett. 2000, 1360.
(4) We assumed oxidative addition occurred with inversion of configuration
as previously reported.5 However, this assumption does not affect the
conclusion of the present work at all.
(7) Solvents were purified with the freeze-pump-thaw method and
solutions were prepared in a glovebox. Thus, complex 1a would not undergo
racemization under the absolutely oxygen free condition.
(8) Recently, we reported the first reversible interconversion between
propargyl and allenylplatinum complexes which occurs spontaneously or is
catalyzed by Pt(0) complexes. (a) Ogoshi, S.; Fukunishi, Y.; Tsutsumi, K.;
Kurosawa, H. J. Chem. Soc., Chem. Commun. 1995, 2485. (b) Ogoshi, S.;
Fukunishi, Y.; Tsutsumi, K.; Kurosawa, H. Inorg. Chim. Acta 1997, 265, 9.
(c) Ogoshi, S.; Nishida, T.; Fukunishi, Y.; Tsutsumi, K.; Kurosawa, H. J.
Organomet. Chem. 2001, 620, 190.
(9) 2a was separately prepared from the reaction of 1 with Pd2(dba)3. See:
Ogoshi, S.; Tsutsumi, K.; Ooi, M.; Kurosawa, H. J. Am. Chem. Soc. 1995,
117, 10415. Ogoshi, S.; Nishida, T.; Tsutsumi, K.; Ooi, M.; Shinagawa, T.;
Akasaka, T.; Yamane, M.; Kurosawa, H. J. Am. Chem. Soc. 2001, 123, 3223.
(5) Elsevier, C. J.; Kleijn, H.; Boersma, J.; Vermeer, P. Organometallics
1986, 5, 716.
(6) The complex 1a was prepared by the reaction of Pd2(dba)3 and PPh3
with (R)-PhCCCH2(Me)Cl (95% ee). Yield 86%. [R]25D +5613° (c 1.34, C6H6).
1H NMR (CDCl3) δ 0.96 (dt, JHH ) 6.8 Hz, JPH ) 1.5 Hz, 3H), 4.04 (q, JHH
) 6.8 Hz, 1H), 6.75 (m, 3H), 7.15 (d, J ) 6.2 Hz), 7.2-7.7 (m, 30H). 31P
NMR (CDCl3) δ 22.83 (d, JPP ) 430.5 Hz), 24.66 (d, JPP ) 430.5 Hz). Anal.
Calcd for C46H39ClP2Pd: C, 69.44; H, 4.94. Found C, 69.24; H, 4.99. For 1b
and 1c, see Supporting Information.
10.1021/ja010583s CCC: $20.00 © 2001 American Chemical Society
Published on Web 06/27/2001

Communications to the Editor
J. Am. Chem. Soc., Vol. 123, No. 29, 2001 7165
Scheme 3. Rapid Allenyl Transfer between 1 and 2 with
Retention
Scheme 4. A Plausible Path for Inversion of Stereochemistry
Figure 2. The plot of kobs vs the ratio of [2b]/[1b]: (A) [1b](A) ) 5.58
× 10-3 M, [2b](A) ) 1.25 × 10-4 M; (B) [1b](B) ) 5.58 × 10-3 M,
[2b](B) ) 2.50 × 10-4 M; (C) [1b](C) ) 5.58 × 10-3 M, [2b](C) ) 4.52
× 10-4 M; (D) [1b](D) ) 8.40 × 10-3 M, [2b](D) ) 4.52 × 10-4 M; and
(E) [1b](E) ) 4.21 × 10-3 M, [2b](E) ) 4.52 × 10-4 M.
time (a few seconds),13,14 which is much faster than the rate of
racemization of 1b in the presence of 2b. This observation
indicates that the allenyl transfer proceeds with the retention of
stereochemistry, otherwise the observed racemization rate should
have been much higher, comparable to the allenyl transfer rate.
Through this transfer, the enantiomeric excess (ee) of 1b is always
equal to that of 2b. According to the scheme, the overall rate is
written as rate ) -d{([1b]0 + [2b]0)(ee)}/dt ) 2kinv[2b]0(ee) and
thus we obtain -d(ee)/dt ) {[2b]0/([1b]0 + [2b]0)}(2kinv)(ee).
completely for 2 h, presumably owing to the role of additional
PPh3 to prevent the generation of 2a by forming Pd(PPh3)n (n )
1
3 or 4).10 In support of this assumption, the H and 31P NMR
spectra of the concentrate of the solution of 1a and added PPh3
which had been kept under air for 2 h showed no formation of
dinuclear complex 2a, although the production of very small
amounts of OdPPh3 and 1-phenyl-4-buten-1-yne was confirmed.
From the above results, we suspected that the dinuclear
complex is the catalyst or mediator for the racemization of 1a or
1b. In fact, we found that addition of the dinuclear complex 2a
or 2b accelerated the racemization of 1a or 1b (under N2) in
CHCl3 at 25 °C efficiently; the plot of -ln[R/R0] vs time gave a
straight line over 3 half-lives (Figure 1) (1a: kobs ) 3.0 × 10-4
s-1 at [1a] ) 1.53 × 10-3 M and [2a] ) 1.53 × 10-4 M; 1b:
kobs ) 2.5 × 10-5 s-1 at [1b] ) 7.59 × 10-3 M and [2b] ) 7.59
× 10-4 M; -dR/dt ) kobsR). Interestingly, racemization of
optically more stable complex 1c was also accelerated by addition
of the dinuclear complex 2c (kobs ) 1.1 × 10-5 s-1 at [1c] )
2.19 × 10-2 M and [2c] ) 2.25 × 10-3 M).
On the other hand, since kobs is determined from -dR/dt ) kobs
R
and R can be written as R ) (constant)(ee), we can obtain the
equation -d(ee)/dt ) kobs(ee).15 Thus, the following relationship
between kobs and kinv can be obtained, kobs) {[2b]0/([1b]0
+
[2b]0)}2kinv, which is in accordance with Figure 2 if [2b]0 in the
denominator is neglected.16 The rate constant (2kinv) for the
racemization of the dinuclear complex is expected to be much
17
larger than kobs
.
Likely candidates for such inversion in the
dinuclear complex include the formation of a nonchiral µ-η1:η1-
vinyldipalladium intermediate18 (Scheme 4).
By referring to the overall scheme presented here, we could
give a criterion for the palladium-catalyzed asymmetric reaction
of propargyl electrophiles; the generation of the dinuclear complex
should be designed to meet the dynamic kinetic resolution, for
example, by decreasing the amount of phosphine ligand, or be
suppressed to avoid the loss of optical purity of the substrate by
adding an excess amount of ligand.
To understand how the dinuclear complex participates in the
racemization, the rate of the decrease in the optical rotation was
measured at 40 °C at several concentrations of 1b and 2b with
[2b] being less than 1/10 of [1b].12 The rate constant kobs was
linearly dependent on the concentration of 2b, if the concentration
of 1b was kept constant (Figure 2, A-C), which suggests that
2b might be the catalyst for the racemization. More remarkably,
however, kobs was linearly dependent on the inverse of the
concentration of 1b, if the concentration of 2b was kept constant
(Figure 2, C-E). This leads us to believe that the inversion of
stereochemistry of the allenyl ligand does not occur simply in an
association complex involving 1 and 2; otherwise kobs should be
independent of the initial concentration of 1.
Further efforts related to this problem are underway in this
laboratory.
Acknowledgment. Partial support of this work through CREST of
the Japan Science and Technology Corporation and Grants-in-Aid for
Scientific Research from Ministry of Education, Science and Culture,
Japan is gratefully acknowledged.
Supporting Information Available: Procedures and spectral data for
complexes 1a-c and 2a-c, and measurement for the decrease of optical
rotation (PDF). This material is available free of charge via the Internet
at http://pubs.acs.org.
JA010583S
We now propose the occurrence of rapid exchange of the
allenyl ligand between 1 and 2 with retention of stereochemistry
(Scheme 3) and rate determining inversion in the dinuclear
complex 2 (Scheme 4). We confirmed by the spin saturation
transfer experiment at 40 °C that the rate of allenyl group
exchange between 1b and 2b is on the order of 1H spin relaxation
(13) Transfer of Pd(0) from dinuclear complex to mononuclear complex
can give rise to the virtual allenyl transfer between 1 and 2.
(14) Irradiation at the resonance frequency of the allenyl proton in 2b
resulted in a decrease (1.48%) of the signal due to allenyl proton in 1b. A
similar equilibrium between mononuclear and dinuclear complexes of η3-
allylpalladium had been reported. Kurosawa, H.; Hirako, K.; Natsume, S.;
Ogoshi, S.; Kanehisa, N.; Kai, Y.; Sakaki, S.; Takeuchi, K. Organometallics
1996, 15, 2089.
(10) The reaction of Pd(PPh3)4 with mononuclear allenyl/propargylpalla-
dium does not lead to the formation of dinuclear complex, and addition of
excess PPh3 to the dinuclear complex results in the re-formation of the
mononuclear complex and Pd(PPh3)n (n ) 3 or 4).9 In fact, Pd(PPh3)4 (10
mol %) was not effective at all in promoting racemization of 1a and 1b in
contrast to Pd(0)-catalyzed loss of stereochemistry of η3-allylpalladium.11
(11) (a) Ogoshi, S.; Kurosawa, H. Organometallics 1993, 12, 2869. (b)
Kurosawa, H.; Ogoshi, S.; Chatani, N.; Kawasaki, Y.; Murai, S.; Ikeda, I.
Chem. Lett. 1990, 1745. (c) Granberg, K. L.; Ba¨ckvall, J. E. J. Am. Chem.
Soc. 1992, 114, 6858.
(15) R ) RM + RD ) ([RM][1]0 + [RD][2]0)ee ([RM] and [RD] being specific
rotations of mononuclear and dinuclear complexes, respectively).
(16) The plot of kobs vs the ratio [2b]0/([1b]0 + [2b]0) also gives a straight
line (slope ) 1.24 × 10-2 s-1, while that of Figure 2 is 1.11 × 10-2 s-1).
(17) We could not isolate the optically active dinuclear complex due to
the expected rapid inversion of the stereochemistry on Pd(I)-Pd(I) even in
the configurationally most stable complex 2c (kinv ) 9.6 × 10-4 s-1 at 25
°C).
(18) A µ-η1:η1-vinyl complex similar to this intermediate has been known.
Al-Obaidi, Y. N.; Green, M.; White, N. D.; Taylor, G. E. J. Chem. Soc., Dalton
Trans. 1982, 319.
(12) Decrease of optical rotation was measured at 40 °C due to the ease of
accurate temperature control for long hours.