aldehyde occurs in the absence of a catalyst.5 In reactions
of imines, tandem catalysis occurs, with a palladium complex
catalyzing both allylboronate formation and subsequent imine
allylation. In addition, hexamethylditin has been used in
allylations using allylic halides.6
We have recently identified several palladium complexes
that catalyze the addition of allylic silanes to imines (Scheme
1b).7,8 Palladium-catalyzed synthesis of allylic silanes from
optimized reaction conditions, one-pot reaction of allyl
trifluoroacetate with hexamethyldisilane and imine 1a af-
forded 74% yield of homoallylic amine (eq 1). The palladium
catalyst is required for both transformations: no homoallylic
amine 2a was formed in control experiments using preformed
allylsilane, TBAF, and trimethylsilyl trifluoroacetate in the
absence of palladium complexes.
Scheme 1
.
Development of a One-Pot Allylation Reaction
Using Allyltrifluoroacetate
A variety of aromatic aldimines react under the optimized
reaction conditions (Table 1). Electron-poor aromatic imines
Table 1. Allylation of Imines with Allyl Trifluoroacetate and
Hexamethyldisilanea
trifluoroacetates has been reported (Scheme 1a).9 We rea-
soned that both transformations could be performed in the
same reaction vessel using the same catalyst (Scheme 1c).
To meet our objectives, the palladium complex would
catalyze both allylsilane formation and allylation of the imine
in a one-pot reaction.
A set of reaction conditions that would be suitable for both
transformations was determined by examining allylsilane
formation and allylation of imine 1a separately.10,11 Under
a 2.0 equiv of hexamethyldisilane, 2.0 equiv of allyl trifluoroacetate, 5
mol % palladium acetate, toluene, room temperature, 2 h, then 1.0 equiv
of imine, 4.0 equiv of TBAF (1.0 M in THF), room temperature, 22 h. See
Supporting Information for full experimental details. b Isolated yield after
silica gel column chromatography. c Yield determined by 1H NMR
spectroscopy of the unpurified reaction mixture.
(5) In related studies, enantioselective catalysis of reactions of allenes
affords a chiral allylic boronate that undergoes a stereospecific type I
allylation reaction with aldehydes and imines: (a) Sieber, J. D.; Morken,
J. P. J. Am. Chem. Soc. 2006, 128, 74–75. (b) Woodward, A. R.; Burks,
H. E.; Chan, L. M.; Morken, J. P. Org. Lett. 2005, 7, 5505–5507.
(6) A palladium complex is used to catalyze the formation of allylic
stannanes, which are reacted in one-pot with electrophiles and a second
palladium catalyst to provide the allylated products. (a) Wallner, O. A.;
Szabo´, K. J. Org. Lett. 2004, 6, 1829–1831. (b) Gagliardo, M.; Selander,
N.; Mehendale, N. C.; van Koten, G.; Klein Gebbink, R. J. M.; Szabo´,
K. J. Chem.-Eur. J. 2008, 14, 4800–4809.
afforded the highest yields of products (entries 2-5).
Electron-rich aromatic aldimines and aliphatic aldimines
reacted more sluggishly (e.g., entry 6). Homoallylic alcohol
products predominated for these substrates; these are pre-
sumably generated by hydrolysis of the imine to the aldehyde
with subsequent allylation.
(7) Manuscript in preparation.
To expand the scope of this reaction to include less reactive
substrates, we considered the product distribution of the
palladium-catalyzed allylation reaction. Formation of ho-
moallylic alcohol under the reaction conditions in Table 1
indicated the presence of at least trace quantities of water,12
as water is needed to establish an equilibrium between the
aldimine and aldehyde (Scheme 2). Electron-deficient aldi-
mines reacted quickly with the palladium catalyst (e.g., 1b),
(8) Palladium-catalyzed allylation of imines with allylic silanes: (a)
Nakamura, K.; Nakamura, H.; Yamamoto, Y. J. Org. Chem. 1999, 64, 2614–
2615. (b) Fernandez, R. A.; Yamamoto, Y. J. Org. Chem. 2004, 69, 735–
738
.
(9) (a) Matsumoto, H.; Yako, T.; Nagashima, S.; Motegi, T.; Nagai, Y.
J. Organomet. Chem. 1978, 148, 97–106. (b) Urata, H.; Suzuki, H.; Moro-
oka, Y.; Ikawa, T. Bull. Chem. Soc. Jpn. 1984, 57, 607–608. (c) Tsuji, Y.;
Funato, M.; Ozawa, M.; Ogiyama, H.; Kajita, S.; Kawamura, T. J. Org.
Chem. 1996, 61, 5779–5787.
(10) See Supporting Information for details.
(11) NHC-ligated palladium complexes such as the one shown in Scheme
1b did not catalyze allylsilane formation under these reaction conditions.
In related studies ligation of two monodentate ligands was shown to inhibit
allylsilane formation. See: Macsa´ra, I.; Hupe, E.; Szabo´, K. J. Org. Chem.
(12) The source of the water was inferred to be the commercially
available TBAF. The use of drying agents did not decrease the formation
of homoallylic alcohol. See Supporting Information for details.
1999, 64, 9547–9556
.
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Org. Lett., Vol. 11, No. 2, 2009