Palladium pincer-complex catalyzed allylation of tosylimines by potassium trifluoro(allyl)borates

Article abstract of DOI:10.1021/ol0475010

(Chemical Equation Presented) Palladium pincer complex 1 catalyzes the reaction of trifluoro(allyl)borate 2 with a wide range of tosylimines (3) under mild and neutral reaction conditions. This catalytic transformation affords homoallylic amines (4) in good to excellent yield. Mechanistic studies suggest that a transmetalation reaction between complex 1 and the borate salt 2 provides an η¹-allylpalladium complex, which subsequently reacts with the imine substrate.

Full text of DOI:10.1021/ol0475010

ORGANIC
LETTERS
2
005
Vol. 7, No. 4
89-691
Palladium Pincer-Complex Catalyzed
Allylation of Tosylimines by Potassium
Trifluoro(allyl)borates
6
Niclas Solin, Olov A. Wallner, and K a´ lm a´ n J. Szab o´ *
Stockholm UniVersity, Arrhenius Laboratory, Department of Organic Chemistry,
SE-106 91 Stockhom, Sweden
kalman@organ.su.se
Received December 6, 2004
ABSTRACT
Palladium pincer complex 1 catalyzes the reaction of trifluoro(allyl)borate 2 with a wide range of tosylimines (3) under mild and neutral
reaction conditions. This catalytic transformation affords homoallylic amines (4) in good to excellent yield. Mechanistic studies suggest that
1
a transmetalation reaction between complex 1 and the borate salt 2 provides an
the imine substrate.
η
-allylpalladium complex, which subsequently reacts with
Allylpalladium chemistry is one of the most successful areas
in transition-metal catalysis. In the most common application
of this methodology, an allylpalladium intermediate is
active allylpalladium species are usually generated in a
transmetalation reaction between an allylstannane and a
palladium complex. Because of the toxicity of organo-tin
reagents, and the tedious separation of the tin-containing
1
generated, which subsequently reacts with nucleophiles.
4
Recently, however, possibilities to extend allylpalladium
chemistry to electrophilic substrates have attracted much
attention, as certain allylpalladium species2,3 have been shown
to react with electrophiles. In these catalytic reactions, the
byproducts, it would be desirable to replace the allylstannane
5
component of the reaction with other allylmetal species. We
have now found that in palladium-catalyzed electrophilic
substitution reactions allylstannanes can be replaced by
6
potassium trifluoro(allyl)borate 2. Thus, palladium pincer
(
1) (a) Tsuji, J. Palladium Reagents and Catalysts: InnoVations in
complex 1 catalyzes the allylation of tosylimines 3 with the
borate salt 2 (Scheme 1). A wide range of tosylimines (3a-
i) can be allylated by this procedure in good to excellent
yields (Table 1).
Organic Synthesis; Wiley: Chichester, 1995. (b) Hegedus. L. S. Transition
Metals in the Synthesis of Complex Organic Molecules; University Science
Books: Mill Valley, CA, 1999.
(
2) (a) Nakamura, K.; Iwama, H.; Yamamoto, Y. J. Am. Chem. Soc. 1996,
1
18, 6641. (b) Nakamura, H.; Shim, J.-G.; Yamamoto, Y. J. Am. Chem.
Soc. 1997, 119, 8113. (c) Nakamura, H.; Nakamura, K.; Yamamoto, Y. J.
Am. Chem. Soc. 1998, 120, 4242. (d) Nakamura, K.; Nakamura, H.;
Yamamoto, Y. J. Org. Chem. 1999, 64, 2614. (e) Nakamura, H.; Kouichi,
A.; Shim, J.-G.; Yamamoto, Y. J. Am. Chem. Soc. 2001, 123, 372. (f)
Fernandes, R. A.; Stimac, A.; Yamamoto, Y. J. Am. Chem. Soc. 2003, 125,
(3) (a) Solin, N.; Kjellgren, J.; Szab o´ , K. J. Angew. Chem., Int. Ed.
2003, 42, 3656. (b) Solin, N.; Kjellgren, J.; Szab o´ , K. J. J. Am. Chem.
Soc. 2004, 126, 7026. (c) Wallner, O. A.; Szab o´ , K. J. Org. Lett. 2004, 6,
1829.
(4) Farina, V.; Krishnamurthy, V.; Scott, W. J. Org. React. 1997, 50, 1.
(5) For possiblities to replace allylstannanes with allylsilanes see ref
2d.
(6) (a) Batey, R. A.; Thadani, A. N.; Smil, D. V. Tetrahedron Lett. 1999,
40, 4289. (b) Batey, R. A.; Thadani, A. N.; Smil, D. V. Lough, A. J.
Synthesis 2000, 990. (c) Thadani, A. N.; Batey, R. A. Org. Lett. 2002, 4,
3827. Thadani, A. N.; Batey, R. A. Tetrahedron Lett. 2002, 44, 8051. (d)
Sze-Wan, L.; Batey, R. A. Chem. Commun. 2004, 1382.
1
4133. (g) Kiji, J.; Okano, T.; Nomura, T.; Saiki, K.; Sai, T.; Tsuji, J. Bull.
Chem. Soc. Jpn. 2001, 74, 1939. (h) Solin, N.; Narayan, S.; Szab o´ , K. J. J.
Org. Chem. 2001, 66, 1686. (i) Solin, N.; Narayan, S.; Szab o´ , K. J. Org.
Lett. 2001, 3, 909. (j) Wallner, O. A.; Szab o´ , K. J. Org. Lett. 2002, 4, 1563.
(k) Wallner, O. A.; Szab o´ , K. J. Chem. Eur. J. 2003, 68, 2934. (l) Wallner,
O. A.; Szab o´ , K. J. Chem. Eur. J. 2003, 9, 4025. (m) Szab o´ , K. J. Chem.
Eur. J. 2000, 6, 4413. (n) For a recent review, see: Szab o´ , K. J.; Chem.
Eur. J. 2004, 10, 5268.
1
0.1021/ol0475010 CCC: $30.25
© 2005 American Chemical Society
Published on Web 01/22/2005

°C. After workup, the crude product was purified by column
chromatography. The reactions were typically carried out at
40 °C (entries 1-6); however, bulky (3f, entry 7) or
deactivated (3g, entry 8) imines required 50 °C reaction
temperature, while activated imines 3h (entry 9) and 3i (entry
Scheme 1. Allylation of Tosylimines by Pincer-Complex
Catalyst 1
1
0) could be allylated at 25 °C. The mild and neutral reaction
conditions are compatible with many functional groups, such
as MeCO, NO , acetals, and CN. In this regard, the imine
2
functionality of 3c and 3h could be selectively allylated in
the presence of the cyano and keto groups. To assess the
stereochemistry of the catalytic allylation reaction we reacted
6b
3
a with (E)-crotyltrifluoroborate (Scheme 2). This reaction,
In a typical procedure, the imine 3 (0.10 mmol), borate
salt 2 (0.11 mmol) and pincer complex 1 (0.005 mmol, 5
mol %) in DMF (300 µL) were reacted for 24 h at 25-50
Scheme 2. Catalytic Allylation Using (E)-Crotyltrifluoroborate
Substrate
Table 1. Palladium-Catalyzed Allylation of Tosyliminesa
however, proceeds with a poor yield and stereoselectivity.
2
We also tested Pd(OAc) as catalyst anticipating the
formation of a bis-allylpalladium intermediate, which would
2
j
be able to allylate imine 3a. Using 5 mol % Pd(OAc)
2
and
, imine 3a was allylated in 66% yield (entry
). Use of PPh proved to be indispensable to get an
alone or other phosphine free
catalysts (such as [Pd(allyl)Cl] ) gave a low conversion of
a.
We have also performed a control experiment using the
5
2
mol % PPh
3
3
acceptable yield, as Pd(OAc)
2
2
3
reaction conditions given in entry 1 without adding palladium
catalyst (Scheme 3). In this experiment, homoallylic amine
Scheme 3. Reactions in the Absence of Palladium Catalyst 1
4
a was not formed at all. The only product observed in this
reaction was a trace of homoallyl alcohol. This product is
probably formed by the reaction of benzaldehyde (resulted
from partial hydrolysis of the imine) and 2.
6
d
Mechanistic Aspects. Batey and Sze-Wan showed that
tosylimines are allylated in excellent yield by two equivalents
of borate salt 2 in CH
2
Cl
2
using 5 mol % of BF
3 2
‚Et O as
Lewis acid catalyst. We have attempted to perform this Lewis
acid-catalyzed reaction with 3a and 2 in DMF (Scheme 3);
however, we did not observe any formation of the desired
homoallylamine product (4a). This probably can be explained
a
by the deactivation of the employed Lewis acid (BF
2
‚Et O)
Unless otherwise stated, the reactions were conducted in DMF for 24
3
h using 5 mol % of complex 1 as catalyst and 1.1 equiv of borate salt 2.
Isolated yield. 5 mol % of Pd(OAc)2 and 5 mol % of PPh3 were used as
catalyst.
by the DMF solvent. A clear advantage of using 1 as catalyst
is that application of 1.1 equiv. of 2 is sufficient to obtain
b
c
high yields, while employment of Lewis acid catalyst BF ‚
3
690
Org. Lett., Vol. 7, No. 4, 2005

1
complex 1 reacts with allylstannanes to form η -allylpalla-
dium complex 6. Therefore, the fact that either of allylstan-
nane 5 or borate salt 2 gives the same product when reacted
with complex 1 strongly indicates that 2 also undergoes a
transmetalation reaction with complex 1 resulting in (η -
allyl)palladium complex 6 (Scheme 4). Complex 6 subse-
quently undergoes electrophilic attack by tosylimine 33
affording homoallylic amines 4.
Scheme 4. Stoichiometric Reactions with Pincer Complex 1
and Allylmetal Reagents 2 and 5
7
1
In summary, we have developed a palladium pincer-
complex catalyzed allylation reaction, where tosylimines
were allylated with borate salt 2. This reaction is assumed
2
Et O requires the use of 2 equiv of the allylic substrate (2).
1
to proceed via (η -allyl)palladium intermediate (6). Applica-
On the other hand, Batey’s conditions give higher yield and
stereoselectivity with crotyltrifluoroborate, than the pincer-
complex catalyzed reaction (Scheme 2).
tion of this procedure eliminates the use of toxic tin
compounds, thereby extending the synthetic utility of the
palladium catalyzed electrophilic substitution reaction.
To gain more mechanistic insights into the above catalytic
process (Scheme 1), we monitored the stoichiometric reaction
Acknowledgment. This work was supported by The
Swedish Research Council (VR).
3
1
of 1 and 2 by P NMR spectroscopy. Complex 1, dissolved
in a mixture of DMF/C (10:1), was reacted with 2 at room
6 6
D
Supporting Information Available: Experimental pro-
temperature (Scheme 4). Addition of 2 led to a decrease of
the 31P NMR peak of 1 at δ 146.0 ppm, while a new peak
appeared at δ 148.4 ppm clearly indicating a reaction
between the palladium complex (1) and the allylic substrate
1
13
cedures, NMR data, as well as H and C NMR spectra of
products 4a-j. This material is available free of charge via
the Internet at http://pubs.acs.org.
(2). To clarify the nature of this reaction we performed a
OL0475010
similar stoichiometric experiment using allylstannane (5) in
place of 2 (Scheme 4). In this process we observed again a
(7) For studies on the transmetalation reaction between palladium
complexes and potassium trifluoro(organo)borates, see: (a) Molander, G.
A.; Bialatto, B. J. Org. Chem. 2003, 68, 4302. (b) Darses, S.; Genet, J.-P.
Eur. J. Org. Chem. 2003, 4313.
31
downfield shift by δ 2.4 ppm of the P NMR shift of
complex 1. In a recent study we have shown3b that pincer
Org. Lett., Vol. 7, No. 4, 2005
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