Snapshots of a Stille reaction

Article abstract of DOI:10.1039/b008811k

The main sequential intermediates involved in a real catalytic cycle of the Stille reaction (the coupling of ROTf with CH₂=CHSnBu₃ catalyzed by [PdR(OTf)(dppe)]; R = aryl) are observed and characterized unequivocally before the coupling product is released.

Full text of DOI:10.1039/b008811k

Snapshots of a Stille reaction
Arturo L. Casado, Pablo Espinet,* Ana M. Gallego and Jesús M. Martínez-Ilarduya
Departamento de Química Inorgánica, Facultad de Ciencias, Universidad de Valladolid, E-47005 Valladolid, Spain.
E-mail: espinet@qi.uva.es
Received (in Liverpool, UK) 1st November 2000, Accepted 12th January 2001
First published as an Advance Article on the web 31st January 2001
The main sequential intermediates involved in a real
catalytic cycle of the Stille reaction (the coupling of ROTf
with CH2NCHSnBu3 catalyzed by [PdR(OTf)(dppe)]; R =
aryl) are observed and characterized unequivocally before
the coupling product is released.
Only in rare occasions can real intermediates in a catalytic cycle
be observed and unambiguously identified. The Stille reaction
(palladium-catalyzed coupling of organotin reagents with
carbon electrophiles) is nowadays one of the most powerful
synthetic methods for the formation of carbon–carbon bonds.1
Its catalytic cycle involves a number of intermediates, but
evidence for these only comes from model reactions outside a
real cycle. Echavarren and coworkers have synthesized oxa-
and aza-palladacycles using the oxidative addition of haloaryl-
stannanes to Pd(0) complexes, followed by an intramolecular
transmetalation, thus the products can be considered inter-
mediates of a frustrated Stille cycle, which do not undergo
coupling because of the high energy of the coupling product.2
We have shown that the coupling of halides R1I with SnR2Bu3
(R2 = vinyl or phenyl) follows a SE2 mechanism involving an
associative L-for-R2 substitution on trans-[PdR1IL2]. This
Pd(II) complex, which can be prepared separately, was actually
observed as involved in the catalytic cycle.3 More recently we
have observed the formation and fading out of trans-
[PdR1R2L2] in the coupling of triflates R1OTf with Sn(vi-
nyl)Bu3.4 Here we present a catalytic Stille coupling in which
all the main intermediates involved are observed, as they are
1
formed and disappear, using H, 19F and 31P NMR spectros-
copy.
[Pd(C6F5)(OTf)(dppe)] 1a [dppe = 1,2-bis(diphenylphos-
phino)ethane] is a poor catalyst for the coupling, in THF at
50 °C (Pd+Sn = 1+20), of C6F5OTf and CH2NCHSnBu3 2 to
give CH2NCHC6F5. When the reaction was carried out in THF-
d8 at low temperature, starting with [Pd(C6F5)(OTf)(dppe)] and
CH2NCHSnBu3 in 1+1 molar ratio, several intermediate species
could be detected and identified until the coupling product was
formed. For an easier monitoring of the cycle the studies were
repeated on [Pd(C6Cl2F3)(OTf)(dppe)] 1b (C6Cl2F3 = 3,5-di-
chlorotrifluorophenyl), which behaves identically to 1a and
shows the same intermediates, but has more simple 19F NMR
spectra, facilitating a more accurate integration of the signals.5
Scheme 1 Catalytic cycle showing the 1H NMR spectra of the products
detected in the range of vinylic protons.
Scheme 1 shows, step by step, the mechanism of the catalytic
cycle and the 1H NMR spectra of the intermediates identified in
the stoichiometric cycle for 1b while Fig. 1 shows the evolution
of the reaction, as monitored by 19F NMR.
The first intermediate in the cycle is 1a (or 1b). Under
catalytic conditions 1a is formed very slowly by oxidative
addition of C6F5OTf to [Pd(0)], but stoichiometrically these
compounds are better prepared from [PdRCl(dppe)] (R = C6F5,
C6Cl2F3) and AgOTf. Complexes 1a and 1b are stable in the
solid state and have been isolated and fully characterized.6 In
solution in dry THF they give the ionic species [PdR(dppe)-
(THF)](OTf) (specific molar conductivity, Lm = 4.66 S cm21
mol21 for 1a),7 on which the transmetallation occurs.4
The next step is the transmetalation on 1b leading to a s-vinyl
complex [Pd(C6Cl2F3)(CHNCH2)(dppe)] 3, characterized by
NMR. Its 19F NMR spectrum shows the characteristic reso-
nances expected for a C6Cl2F3 group linked to Pd(II), with the
Fortho coupled to the trans phosphorus atom (coupling to the cis
phosphorus is not observed). In the 31P{1H} NMR spectrum
two signals are observed: one for the P trans to C6Cl2F3, which
appears as an overlapped doublet of triplets, and one for the cis
phosphorus which appears as a doublet. The 1H NMR spectrum
(Scheme 1) shows three resonances for the three vinylic
protons, coupled to phosphorus (see changes upon 31P irradia-
tion in the corresponding 1H{31P} NMR spectrum).
Complex 3 is unstable and can be observed only at low
temperature.8 In spite of the cis configuration of this complex,
the reductive elimination step takes place less easily than with
PPh3 because of the small bite angle chelating ligand,9 and this
stabilizes the compound sufficiently for it to be observed.10 The
DOI: 10.1039/b008811k
Chem. Commun., 2001, 339–340
This journal is © The Royal Society of Chemistry 2001
339

Notes and references
1 (a) V. Farina, V. Krishnamurthy and V. J. Scott, The Stille Reaction, in
Organic Reactions, 1997, vol. 50, p. 1; (b) V. Farina, V. Krishnamurthy
and V. J. Scott, The Stille Reaction, Wiley, New York, 1999; (c) S. P.
Stanforth, Tetrahedron, 1998, 54, 263; (d) V. Farina and G. P. Roth,
Adv. Met-Org. Chem., 1996, 5, 1; (e) T. N. Mitchell, Synthesis, 1992,
803; (f) J. K. Stille, Angew. Chem., Int. Ed. Engl., 1986, 25, 508.
2 D. J. Cárdenas, C. Mateo and A. M. Echavarren, Angew. Chem., Int. Ed.
Engl., 1994, 33, 2445; C. Mateo, D. J. Cárdenas, C. Fernández-Rivas
and A. M. Echavarren, Chem. Eur. J., 1996, 2, 1596.
3 A. L. Casado and P. Espinet, J. Am. Chem. Soc., 1998, 120, 8978.
4 A. L. Casado, P. Espinet and A. M. Gallego, J. Am. Chem. Soc., 2000,
122, 11771.
5 M. A. Alonso, J. A. Casares, P. Espinet, J. M. Martínez-Ilarduya and C.
Pérez-Briso, Eur. J. Inorg. Chem., 1998, 1745.
6 1a and 1b were prepared from their corresponding precursors,12 by
treatment of [PdRCl(dppe)] with AgOTf, removal of the AgCl led to
crystallisation. 1a: yield: 89%; calc. for C33H24F8O3P2PdS: C, 48.28; H,
2.95; found: C, 48.62, H 3.17%; 19F NMR (ref. CFCl3, CDCl3–THF), d
278.22/274.71 (s, CF3), 2118.52/2113.70 (m, o-CF),
Fig. 1 Profiles of the reaction between [Pd(C6Cl2F3)(OTf)(dppe)] 1b and
CH2NCHSnBu3 2 in THF at 243 K. Concentrations were obtained by
integration in the 19F NMR spectra. Starting concentration: 0.02 mol L–1 in
1b.
3
2158.88/2157.76 (t, JFF 19.5 Hz, p-CF), 2162.50/2160.43 (m, m-
CF); 31P{1H} NMR (ref. 85% H3PO4, CDCl3–THF), d 61.9/67.9 (m,
Pcis), 46.3/52.6 (m, Ptrans); 1H NMR (300 MHz, ref. TMS, CDCl3), d
7.85–7.40 (m, arom-CH), 2.57 (m, CH2), 2.19 (m, CH2). 1b: yield: 87%;
calc. for C33H24Cl2F6O3P2PdS: C, 46.42, H, 2.83%; found: C 46.28, H,
coupling product remains coordinated stabilizing a Pd0 complex
2
[Pd(dppe)(h -CH2NCHC6Cl2F3)] 4. Its 1H NMR spectrum
2.83%; 19F NMR (CDCl3–THF),
d 278.19/274.72 (s, CF3),
(Scheme 1) shows three broadened signals, at higher field than
in the s-vinyl complex 3 due to the bigger shielding produced
by the metallic center. They are coupled to each other (as seen
4
4
292.46/287.43 (dd, JFP(trans) 13.5, JFP(cis) 7.5 Hz, o-CF),
2117.26/2115.14 (s, p-CF); 31P{1H} NMR (CDCl3–THF), d 61.6/67.5
(dt, 2JPP 15.5, 4JFP 7.5 Hz, Pcis), 46.0/51.7 (dt, 2JPP 15.5, 4JFP 13.5 Hz,
1
by H COSY) and also coupled with the phosphorus nuclei of
1
Ptrans); H NMR (CDCl3), d 7.85–7.43 (m, arom-CH), 2.55 (m, CH2),
the dppe ligand. In the 1H{31P} NMR spectrum (Scheme 1) only
the coupling between protons is observed. The 31P NMR
spectrum of 4 shows an AB system. This chemical in-
equivalence of the two P atoms is consistent with a trigonal-
planar coordination of the palladium, with the double bond of
the asymmetric olefin lying in the plane containing the
palladium atom and two phosphorus atoms. Similar complexes
have been reported in the literature.11 This compound is again
rather stable and can be observed even at room temperature in
the stoichiometric reaction. Upon decomposition (or when it
undergoes oxidative addition) the olefin CH2NCHC6Cl2F3 5 is
released.
2.18 (m, CH2).
7 The formation of very similar ionic complexes, with either THF or H2O
displacing the triflate, has been reported, and similar molar conductivity
values have been found: J. M. Brown and K. K. Hii, Angew. Chem., Int.
Ed. Engl., 1996, 35, 657–659.
8 NMR characterization of the intermediates: 3: 19F NMR (THF, 243 K),
4
d 285.41 (d, JFP 10.8 Hz, o-CF), 2119.11 (s, p-CF); 31P{1H} NMR
(THF, 243 K), d 47.2 (dt, 2JPP 21.3, 4JFP 10.8 Hz, Ptrans), 44.0 (d, 2JPP
21.3 Hz, Pcis); 1H NMR ([D8]THF, 243 K), d 8.00–6.88 (m, arom-CH),
6.83 (m, transJHH 18.3, cisJHH 10.9, 3JHP(trans) 10.9, 3JHP(cis) 8.3 Hz, CH),
5.49 (dddd, cisJHH 10.9, gemJHH 2.2, 4,transJHP(trans) 25.1, 4JHP(cis) 2 Hz,
trans
gem
4,cis
CH), 4.84 (ddd,
J
18.3,
J
2.2,
J
11.7 Hz, CH),
HH
HH
HP(trans)
3.00 (br, CH2), 2.40 (br, CH2). 4: 19F NMR (THF, 243 K), d 2114.64
(s, o-CF), 2123.24 (s, p-CF); 31P{1H} NMR (THF, 243 K), d 42.5 (d,
2JPP 48.4 Hz, P), 38.7 (d, 2JPP 48.4 Hz, P); 1H NMR ([D8]THF, 243 K),
d 7.85–6.80 (m, arom-CH), 4.49 (br. m,
3JHP(trans) 9.5 Hz, CH), 3.72 (br, transJHH 12.5 Hz, CH), 2.98 (br, cisJHH
In catalytic conditions the cycle should close upon oxidative
addition to 4 or to a low coordinated [Pd(0)] complex formed by
decoordination of 5. This oxidative addition is extremely slow
and decomposition pathways compete, causing the low effi-
ciency of the catalyst.11a However, four to five turnovers are
observed showing that the cycle is actually catalytic. Alter-
natively, the oxidative addition step can be accelerated very
efficiently by adding LiCl once 4 has been formed [the
accelerating effect of LiCl on some Stille catalytic cycles is well
documented in ref. 1(a), and is discussed in ref. 11(a)]. This
leads to the easy formation of [PdRCl(dppe)] on which,
however, transmetalation is extremely slow. A thorough
discussion of these observations will be made in a forthcoming
full paper.
This article is dedicated to Professor Rafael Usón on occasion
of his 75th birthday. The work was supported by the Dirección
General de Investigación Científica y Técnica (Project No.
PB9620363) and the Junta de Castilla y León (Project No.
VA80-99). A. M. G. is grateful for a grant from the Dirección
General de Enseñanza Superior (Spain).
trans
cis
J
12.5,
J
9.6,
HH
HH
9.6 Hz, CH), 2.50 (br, CH2), 2.10 (br, CH2).
9 G. Mann, D. Baranano, J. F. Hartwig, A. L. Rheingold and I. A. Guzei,
J. Am. Chem. Soc., 1998, 120, 9205, and references therein.
10 A similar complex [Pd(CH2Ph)(CHNCHC6H4OMe-p)(dppf)] [dppf =
1,1A-bis(diphenylphosphino)ferrocene],
obtained
treating
[PdBr(CHNCHC6H4OMe-p)(dppf)] with ClMgCH2Ph at 270 °C, has
been detected previously: N. A. Cooley and J. M. Brown, Organome-
tallics, 1990, 9, 353. In that case its observation is likely facilitated by
the slower elimination when sp3 carbons are involved: M. J. Calhorda,
J. M. Brown and N. A. Cooley, Organometallics, 1991, 10, 353.
11 (a) A. Jutand, K. K. Hii, M. Thornton-Pett and J. M. Brown,
Organometallics, 1999, 18, 5367; (b) J. Krause, W. Bonrath and K. R.
Pörschke, Organometallics, 1992, 11, 1158; (c) F. Ozawa, T. Ito, Y.
Nakamura and A. Yamamoto, J. Organomet. Chem., 1979, 168, 375.
12 [PdRCl(dppe)] (R = C6F5, C6Cl2F3) were prepared by a general method
reported previously: P. Espinet, J. M. Martínez-Ilarduya, C. Pérez-
Briso, A. L. Casado and M. A. Alonso, J. Organomet. Chem., 1998, 551,
9.
340
Chem. Commun., 2001, 339–340