A SeCSe-Pd(II) pincer complex as a highly efficient catalyst for allylation of aldehydes with allyltributyltin

Article abstract of DOI:10.1021/jo060456k

An air- and moisture-stable SeCSe-Pd(II) pincer complex was synthesized and found to catalyze the nucleophilic allylation of aldehydes with allyltributyltin. The allylation of a variety of aromatic and aliphatic aldehydes to give the corresponding homoall

Full text of DOI:10.1021/jo060456k

SCHEME 1. Allylation of Aldehydes with Allylmetals
A SeCSe-Pd(II) Pincer Complex as a Highly
Efficient Catalyst for Allylation of Aldehydes
with Allyltributyltin
Qingwei Yao* and Matthew Sheets
Department of Chemistry and Biochemistry, The Michael
Faraday Laboratories, Northern Illinois UniVersity,
DeKalb, Illinois 60115-2862
qyao@niu.edu
ReceiVed March 2, 2006
combination with NaI, has recently been introduced as a new,
stoichiometric promoter for the allylation of various aldehydes
with allyltributyltin.5 Yamamoto and co-workers first reported
the Pt- and Pd-catalyzed allylation of aldehydes and imines with
allyltributyltin (Scheme 1, eq 2).6 They demonstrated that a
π-allyl-σ-allylpalladium complex in equilibrium with an iso-
meric bis-π-allylpalladium complex served as the nucleophilic
allyl transfer species. Recently, pincer complexes7 of Rh and
Pd have been reported as efficient catalysts for this reaction
(Scheme 1, eq 3).8 While the NCN-Rh pincer complex used
in Nishiyama’s catalyst system8a was believed to function as a
Lewis acid, results from the body of Szabo´’s work8b-d point to
the likelihood of a nucleophilic allylpalladium intermediate
formed by transmetalation with the tin reagent.6,9,10
An air- and moisture-stable SeCSe-Pd(II) pincer complex
was synthesized and found to catalyze the nucleophilic
allylation of aldehydes with allyltributyltin. The allylation
of a variety of aromatic and aliphatic aldehydes to give the
corresponding homoallyl alcohols was performed at room
temperature to 60 °C in yields ranging from 50% (for typical
aliphatic aldehydes) to up to 97% (for aromatic aldehydes)
using 5 × 10-3 to 1 mol % of the Pd catalyst. NMR
spectroscopic study indicated that a σ-allylpalladium inter-
mediate was formed and possibly functions as the nucleo-
philic species that undergoes addition to the aldehydes.
We have recently reported the synthesis of the first selenium-
ligated palladium pincer complex 1 and the related Se-ligated
(2) (a) Yamamoto, Y.; Yatagai, H.; Naruta, Y.; Maruyama, K. J. Am.
Chem. Soc. 1980, 102, 7107. (b) Pereyre, M.; Quintard, J.-P.; Rahm, A.
Tin in Organic Synthesis; Butteworths: London, 1987; p 216. (c) Davies,
A. G. Organotin Chemistry; Wiley-VCH: Weinheim, Germany, 2004;
Chapter 5.
(3) Selected recent examples. Ag-based catalysts: (a) Yanagisawa, A.;
Nakashima, H.; Ishiba, A.; Yamamoto, H. J. Am. Chem. Soc. 1996, 118,
4723. (b) Yanagisawa, A.; Ishiba, A.; Nakashima, H.; Yamamoto, H. Synlett
1997, 88. Zn-based catalysts: (c) Cozzi, P. G.; Orioli, P.; Tagliavini, E.;
Umani-Ronchi, A. Tetrahedron Lett. 1997, 38, 145. (d) Imai, Y.; Zhang,
W.; Kida, T.; Nakatsuji, Y.; Ikeda, I. J. Org. Chem. 2000, 65, 3326. (e)
Kwong, H.-L.; Lau, K.-M.; Lee, W.-S.; Wong, W.-T. New J. Chem.1999,
23, 629. Zr-based catalysts: (f) Bedeschi, P.; Casolari, S.; Costa, A. L.;
Tagliavini, E.; Umani-Ronchi, A. Tetrahedron Lett. 1995, 36, 7897. (g)
Casolari, S.; Cozzi, P. G.; Orioli, P. A.; Tagliavini, E.; Umani-Ronchi, A.
Chem. Commun. 1997, 2123. (h) Kurosu, M.; Lorca, M. Tetrahedron Lett.
2002, 43, 1765. (i) Hanawa, H.; Kii, S.; Asao, N.; Maruoka, K. Tetrahedron
Lett. 2000, 41, 5543.
(4) For an excellent recent review, see: Denmark, S. E.; Fu, J. Chem.
ReV. 2003, 103, 2763.
(5) (a) Bartoli, G.; Bosco, M.; Giuliani, A.; Marcantoni, E.; Palmieri,
A.; Petrini, M.; Sambri, L. J. Org. Chem. 2004, 69, 1290. (b) Bartoli, G.;
Giuliani, A.; Marcantoni, E.; Massaccesi, M.; Melchiorre, P.; Lanari, S.;
Sambri, L. AdV. Synth. Catal. 2005, 347, 1673.
(6) (a) Nakamura, H.; Asao, N.; Yamamoto, Y. J. Chem. Soc., Chem.
Commun. 1995, 1273. (b) Nakamura, H.; Iwama, H.; Yamamoto, Y. J. Am.
Chem. Soc. 1996, 118, 6641. Simple Pd(II) or Pt(II) salts, such as PdCl2
and PtCl2, catalyze the allylation of aldehydes with allyltributyltin with
only poor yield; see ref 3a.
(7) Leading recent reviews: (a) Albrecht, M.; van Koten, G. Angew.
Chem., Int. Ed. 2001, 40, 3750. (b) Dupont, J.; Pfeffer, M. Spencer, M.
Eur. J. Inorg. Chem. 2001, 1917. (c) Bedford, R. B. Chem. Commun. 2003,
1787. (d) Singleton, J. T. Tetrahedron 2003, 59, 1837. (e) van der Boom,
M. E.; Milstein, D. Chem. ReV. 2003, 103, 1759. (f) Beletskaya, I. P.;
Cheprakov, A. V. J. Organomet. Chem. 2004, 689, 4055. (g) Dupont, J.;
Consorti, C. S.; Spencer, J. Chem. ReV. 2005, 105, 2527.
Nucleophilic addition of allylmetals to carbonyl compounds
to give the corresponding homoallyl alcohols is a widely
employed and versatile reaction in organic synthesis.1 For stable
allylmetals, such as allylsilanes and allylstannanes, activation
of the carbonyl functionality is often necessary, with various
Lewis acids, in either stoichiometric or catalytic amounts, being
the most widely used promoters (Scheme 1, eq 1).1,2 The past
several years have witnessed an increased interest in the use of
transition metals as catalysts for this powerful transformation.
Several transition-metal-based catalysts have been reported,3
particularly, in the context of catalytic enantioselective allylation
of aldehydes and ketones.4 Such transition-metal-based catalysts
invariably function as a Lewis acid in promoting the allylation
reactions. A lanthanide, cerium(III) chloride (CeCl3•7H2O) in
(1) (a) Yamamoto, Y.; Asao, N. Chem. ReV. 1993, 93, 2207. (b) Marshall,
J. A. Chem. ReV. 1996, 96, 31. (c) Gung B. W. Org. React. 2004, 64, 1. (c)
Roush, W. R. In Comprehensive Organic Synthesis; Heathcock, C. H., Ed.;
Pergamon Press: Oxford, 1991; Vol. 2, pp 1-53. (d) Denmark, S. E.;
Almstead, N. G. In Modern Carbonyl Chemistry; Otera, J., Ed.; Wiley-
VHC: Weinheim, Germany, 2000; Chapter 10. (e) Chemler, S. R.; Roush,
R. W. In Modern Carbonyl Chemistry; Otera, J., Ed.; Wiley-VHC:
Weinheim, Germany, 2000; Chapter 11.
10.1021/jo060456k CCC: $33.50 © 2006 American Chemical Society
Published on Web 06/06/2006
5384
J. Org. Chem. 2006, 71, 5384-5387

TABLE 1. Allylation of Aldehydes with Allyltributyltin 7 Using the SeCSe-Pd Pincer Complex 4 as Catalysta
a All reactions were performed with 1 equiv of 6 and 1.2 equiv of 7 under conditions as indicated. b Referred to isolated yield after column chromatography
on silica gel. c Average of two runs. d The SeCSe-Pd(II) pincer complex 1 was used. e This control reaction was performed in the absence of any catalyst.
1
f Not detected by H NMR. g The Se palladacycle 2 was used.
Complex 4 can be conveniently assembled from the known
bisselenide 511 (Figure 1) and Pd(OAc)2. It was isolated in 82%
yield as an air-stable bright yellow crystalline solid and fully
1
characterized by H and 13C NMR spectroscopy as well as
elemental analysis. The catalytic activity of 4 in the reaction of
aldehydes 6 and allyltributyltin (7) was initially examined using
4-bromobenzaldehyde (6a) as the test substrate in three common
organic solvents: THF, DMF, and DMSO. We were pleased
to find that the reaction proceeded smoothly in the presence of
1 mol % of 4 in THF at room temperature, affording homoallyl
alcohol 8a in high yield (Table 1, entry 1). However, performing
FIGURE 1. Se-ligated Pd complexes.
the reaction at an elevated temperature gave diminished yields
(entry 2). DMF and DMSO proved to be more suitable solvents
for this reaction, allowing the reaction to be carried out at up
to 60 °C (entries 3-8).
Pd(II) complexes 2 and 3 (Figure 1) and demonstrated their
utility in catalysis.11 These Se-Pd(II) complexes are highly
active catalysts for the Heck reaction, outperforming analogous
palladacycles derived from phosphorus-, sulfur-, and nitrogen-
containing ligands. We now wish to report that the SeCSe-
Pd(II) pincer complex 4 can be readily prepared and used as a
highly reactive catalyst for the nucleophilic allylation of
aldehydes with allyltributyltin.
To test the activity scope of 4, the reaction of a number of
other representative aldehydes with 7 were examined in DMF
with different catalyst loading and at different reaction temper-
ature (Table 1). The benchmark benzaldehyde (6b) underwent
allylation uneventfully in the presence of 1 mol % of 4 at either
room temperature or 40 °C (entries 9 and 10). The reaction can
also be performed with much reduced loading of the catalyst
(entries 11 and 12). For example, use of as little as 0.02 mol %
of 4 was found to be sufficient to achieve high conversion when
the reaction was performed at 40 °C. It is interesting to note
that the SeCSe-Pd(II) pincer complex 1,11 the chloride analogue
of 4, gave a much inferior result compared to 4 (entry 13). A
control experiment established that no conversion was observed
(8) (a) Motoyama, Y.; Okano, M.; Narusawa, H.; Makihara, N.; Aoki,
K.; Nishiyama, H. Organometallics 2001, 20, 1580. (b) Solin, N.; Kjellgren,
J.; Szabo´, K. J. Angew. Chem., Int. Ed. 2003, 42, 3656. (c) Solin, N.;
Kjellgren, J.; Szabo´, K. J. J. Am. Chem. Soc. 2004, 126, 7026. (d) Wallner,
O. A.; Szabo´, K. J. Org. Lett. 2004, 6, 1829.
(9) Cotter, W. D.; Barbour, L.; McNamara, K. L.; Hechter, R.; Lachicotte,
R. J. J. Am. Chem. Soc. 1998, 120, 11016.
(10) Franks, R. J.; Nicholas, K. M. Organometallics 2000, 19, 1458.
(11) Yao, Q.; Kinney, E. P.; Zheng, C. Org. Lett. 2004, 6, 2997.
J. Org. Chem, Vol. 71, No. 14, 2006 5385

SCHEME 2. Plausible Mechanistic Pathways for the
Allylation of Aldehydes with Allyltributyltin 7 Catalyzed by
the SeCSe-Pd(II) Pincer Complex 4
labile acetate ligand in 4 when entering into the catalytic cycle.
The marked difference in the reactivity of the aldehyde
substrates revealed by the data in Table 1 points to a relatively
facile transmetalation for the formation of intermediate 9 and a
rate-determining allyl transfer to aldehyde 6. In this regard,
analogues of 4 that would produce a σ-allylpalladium intermedi-
ate with enhanced nucleophilicity of the allyl moiety and/or
increased Lewis acidity of the metal center could be expected
to be even more reactive in catalyzing the allylation reaction.
We have performed a 1H NMR experiment to probe the key
step in the proposed mechanism, the reaction of catalyst 4 with
allyltributyltin 7. When a solution of 4 in deuterated THF was
treated with an excess amount of 7, a single allylpalladium
species 9 (Figure 2) was formed in about 50% conversion after
20 min at 25 °C as monitored by 500 MHz 1H NMR.13 Careful
NMR study using the proton decoupling and proton 2D COSY
techniques established that this transmetalation product has the
structure of a σ-allylpalladium species, denoted as 9-η1. Unlike
the pincer complex 4 that exists as two diastereomeric isomers
(cis- and trans-4), as revealed by the diastereotopic nature of
the benzylic protons on the selenide ligand (SeCH2) of each
diastereomer, 9 exists as a single isomer and its SeCH2 protons
appear as a sharp singlet at δ 4.44 ppm (see Supporting
1
Information for the H NMR spectra of 4 and 9 in THF-d8).14
in the absence of 4 (entry 14). As expected, the electronically
deactivated anisaldehyde (6c) required a higher reaction tem-
perature to achieve a good yield, and the reaction gave slightly
better yield in DMA (entry 17) than in DMF (entry 16). For
activated aldehydes, such as 6d and 6e, the reaction went to
completion after 24 h at room temperature (entries 18 and 22).
When carried out at 40 °C, the reaction would go to completion
with much shorter reaction times and lower catalyst loading
(entries 19-21 and 23). In the case of aldehyde 6d, use of 5.0
× 10-3 mol % of 4 still delivered the product in 80% yield
(entry 21), corresponding to a turnover number (TON) of
15 900. This is, to the best of our knowledge, the highest TON
for the allylation of aldehydes with an allylstannane promoted
by any chemical catalyst. The allylation of aliphatic aldehydes,
such as 6f and 6g, also worked, albeit in lower yields (entries
24 and 25).
Transmetalation to a more reactive allylic metal reagent from
an allylstannane and subsequent nucleophilic addition to car-
bonyls is a well documented process.1 However, examples of
allylation with allylstannanes via catalytic transmetalation by
a transition metal remain rare. Although the possibility that
catalyst 4 functions simply as a Lewis acid catalyst (rather than
a promoter12) in activating the aldehyde cannot be completely
ruled out at this time, a mechanism involving transmetalation
of the tin reagent 7 with 4 to form a nucleophilic σ-allylpalla-
dium species6b,8c,d seems more reasonable. As outlined in
Scheme 2, the catalytic cycle starts with the reaction of 4 and
7 (Path A) to generate the σ-allyl-Pd(II) intermediate 9. This
allyl-Pd species then undergoes nucleophilic addition to
aldehyde 6, probably via a cyclic transition state with the metal
concurrently activating the carbonyl group. The resulting Pd-
(II)-alkoxide intermediate 10 undergoes an exchange reaction
with tributylstannyl acetate to liberate the homoallyl alcohol
product in the form of stannyl ether 11 and to regenerate catalyst
4. Additionally or alternatively, transmetalation may occur at
the stage of intermediate 10 (Path B). If Path B is operating,
the difference in activity between catalyst 4 and its chloride
analogue 1 may be attributed to a faster release of the more
This suggests that the two phenylselenide groups are either free,
spectator ligands or are only loosely associated with the Pd atom
via electronic interaction, providing some electronic and/or steric
stabilization around the metal center. If a tetracoordinated pincer
σ-allyl-Pd complex, 9-η1-Se2, were formed, one would expect
the protons of the SeCH2 groups to be diastereotopic. The release
of the unbound phenylselenide ligands upon formation of the
allylpalladium complex is also consistent with the observation
of an upfield shift of the -SeC6H6 group relative to those found
in 4. The σ-allyl group on Pd is also well resolved. The
R-protons (δ 3.33 ppm) in 9 are about 1.8 ppm downfield
relative to those of 7, whereas the â- and γ-protons of 9 are all
shifted significantly upfield relative to those of 7. This suggests
that 9 possesses a more charge-delocalized anionic allyl group,
and the γ-carbon of the allyl group in 9 is more nucleophilic
than that of 7. Furthermore, we have found no indication by 1H
NMR for the formation or involvement of any type of a
π-allylpalladium complex, such as 9-η3-Se and 9-η3. Although
a dynamic equilibration among these complexes may conceiv-
ably exist, it is clear that structure 9-η1 is the only species that
1
could be observed by H NMR spectroscopy.
The fact that the selenide ligands of the transmetalation
product 9-η1 are not ligated with the metal center also suggests
that the tridentate framework in the pincer complex 4 may not
be a prerequisite for its catalytic activity. To test this hypothesis,
a control experiment was carried out with the SeC palladacycle
2 for the reaction of 7 and benzaldehyde (6b). Interestingly,
the allylation product was isolated in a respectable 74% yield
(Table 1, entry 15), and catalyst 2 is even more reactive in this
reaction than the pincer complex 1 (Table 1, entry 13).
In summary, we have shown that the new SeCSe-Pd(II) pin-
cer complex 4 is a highly efficient catalyst for the allylation of
aldehydes with allyltributyltin. Notable advantage of this catalyst
includes its high stability,15 straightforward synthesis, and superb
catalytic activity compared to other transition catalysts developed
(13) The reaction was found to be very slow when a stoichiometric
mixture of 4 and 7 was used in this NMR experiment.
(14) The 1H NMR assignment of 9 was based on the spectrum obtained
in THF-d8 at -5 °C after 4 reacted with 7 for 20 min at 25 °C. Details of
this NMR study are given in the Supporting Information.
(12) For a clarification of Lewis acid-catalyzed and Lewis acid-promoted
reactions of allylstannanes, see ref 6b.
5386 J. Org. Chem., Vol. 71, No. 14, 2006

1
FIGURE 2. Formation and H NMR data of the allyl-Pd(II) complex 9 from transmetalation between catalyst 4 and allyltributyltin 7.
(major diastereomer) and 133.2 (minor diastereomer), 130.0, 129.8,
129.59, 129.56, and 129.4 (isomeric peaks of 3 C), 124.5 (major
diastereomer) and 124.3 (minor diastereomer), 123.7 (minor dias-
tereomer) and 123.6 (major diastereomer), 43.0 (major diastereomer)
and 42.4 (minor diastereomer), 23.6 (minor diastereomer) and 23.5
(major diastereomer). Anal. Calcd for C22H20O2PdSe2: C, 45.50;
H, 3.47. Found: C, 45.45; H, 3.48.
today for this reaction. The allylation reaction proceeded under
mild and neutral reaction conditions in the presence of only
5.0 × 10-3 to 1 mol % of the catalyst. The results from this
work further demonstrate the potential utility of organic
selenides as alternative ligands in transition metal catalysis.11
Experimental Section
Allylation of Aldehydes with Allyltributyltin in the Presence
of the SeCSe-Pd(II) Pincer Catalyst 4. Representative Proce-
dure: Allylation of 4-Bromobenzaldehyde (6a) with Allyltribu-
tyltin (7) in the Presence of 4 (Table 1, entry 6). A flame-dried
Schlenk flask was charged with aldehyde 6a (92.5 mg, 0.5 mmol),
DMF (0.5 mL), and catalyst 4 (2.9 mg, 0.0050 mmol) under argon.
Allyltributyltin (7) (186 µL, 199 mg, 0.6 mmol) was then added
via syringe. The flask was sealed and heated to 40 °C (bath
temperature) for 18 h. After cooling to room temperature, the
reaction mixture was poured into water and extracted with ether.
The combined extracts were stirred with aqueous KF (10%, w/v)
overnight. The organic layer was then separated, washed with brine,
dried (Na2SO4), and concentrated. The crude product was purified
by flash column chromatography (hexanes/EtOAc 8:1) to give the
known homoallyl alcohol 8a16 (106 mg, 93%) as a colorless oil.
The reaction was repeated one more time, and the product was
isolated in 95% yield.
Synthesis of the SeCSe-Pd(II) Pincer Complex 4. An oven-
dried flask was charged with bisselenide ligand 511 (435 mg, 1.045
mmol) and 1 mL of glacial HOAc. Palladium acetate (236 mg,
1.05 mmol) was then added followed by an additional 1 mL of
HOAc. The reaction mixture was heated to 116 °C and maintained
at gentle reflux for 3 h. After the reaction was cooled to room
temperature and HOAc was removed in vacuo, the crude reaction
product was dissolved in dichloromethane (2 mL). Hexanes (10
mL) were then added, and the product was precipitated as a yellow
crystalline solid. The precipitates were allowed to settle, and the
solvent was decanted. This process was repeated three times, and
the purified product was dried on vacuum line overnight to give
pure 4 (498 mg, 82%) as a bright yellow solid, mp 185-188 °C.
Spectroscopic analysis showed that this material exists as a
diastereomeric mixture in a ratio of 3:2. 1H NMR (500 MHz,
CDCl3): δ 7.98 (dd, J ) 1.86 and 7.7 Hz, major diastereomer)
and 7.91 (d, J ) 7.2 Hz, minor diastereomer) (4 H in total), 7.33-
7.41 (m, 6H), 6.87-6.94 (m, 3H), 4.573 (minor, d, J ) 14.2 Hz)
and 4.568 (d, J ) 13.7 Hz, major diastereomer) (2 H in total),
4.32 (d, J ) 13.7 Hz, major) and 4.21 (d, J ) 14.1 Hz, minor
diastereomer) (2 H in total), 1.84 (br s, minor diastereomer) and
1.71 (br s, major diastereomer) (3 H in total). 13C NMR (125 Hz,
CDCl3): δ 177.2 (minor diastereomer) and 176.9 (major diastere-
omer), 152.7 (minor diastereomer) and 152.3 (major diastereomer),
150.7 (minor diastereomer) and 150.1 (major diastereomer), 133.3
Acknowledgment. We would like to thank Dr. H. Hofstetter
for assistance in the NMR experiments.
Supporting Information Available: Experimental details,
including the NMR spectroscopic study on the reaction of 4 and 7,
spectroscopic data of catalyst 4 and all the products in Table 1.
This material is available free of charge via the Internet at
http://pubs.acs.org.
JO060456K
(15) The isolation, purification, and handling of catalyst 4 are all
performed in open vessels under ambient conditions without special
precautions.
(16) (a) Yanagisawa, A.; Kageyama, H.; Nakatsuka, Y.; Asakawa, K.;
Matsumoto, Y.; Yamamoto, H. Angew. Chem., Int. Ed. 1998, 38, 3701. (b)
Thadani, A. N.; Batey, R. A. Org. Lett. 2002, 4, 3827.
J. Org. Chem, Vol. 71, No. 14, 2006 5387