Three component synthesis of homoallylic amines. Efficient catalysis by lanthanum triflate/benzoic acid

Article abstract of DOI:10.1016/S0040-4039(01)02116-5

Lanthanum triflate-benzoic acid catalyses the in situ formation and allylation of various imines from aldehydes and an aromatic amine.

Full text of DOI:10.1016/S0040-4039(01)02116-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 323–325
Three component synthesis of homoallylic amines.
Efficient catalysis by lanthanum triflate/benzoic acid
Helen C. Aspinall,a James S. Bissett,a Nicholas Greevesa,* and Daniel Levinb
aDepartment of Chemistry, Donnan and Robert Robinson Laboratories, The University of Liverpool, Crown Street,
Liverpool L69 7ZD, UK
bAstraZeneca, Silk Road Business Park, Charter Way, Macclesfield, Cheshire SK10 2NA, UK
Received 20 September 2001; revised 17 October 2001; accepted 5 November 2001
Abstract—Lanthanum triflate–benzoic acid catalyses the in situ formation and allylation of various imines from aldehydes and an
aromatic amine. © 2002 Elsevier Science Ltd. All rights reserved.
In the preceding paper, we reported the lanthanum
triflate–benzoic acid catalyst system for the allylation of
aldehydes with allyltributyltin to give homoallylic alco-
hols.1 We wish to report an extension of the methodol-
ogy to the in situ formation and allylation of imines.
allylated under our conditions, we attempted a one-pot
formation and allylation of the imine again with 5
mol% activated lanthanum triflate. Gratifyingly no
alcohol was seen in the reaction and the amine was
formed exclusively. At this stage the catalyst was still
activated by drying and we were keen to apply our
unactivated catalyst procedure that had been successful
for aldehyde allylations.1 Table 1 shows the results
using unactivated lanthanum triflate catalyst; note the
reduced catalyst loading.
One of the first examples was reported by Keck using
TiCl4 and BF3·OEt2 as catalysts.2 Other developments
in this field have seen the use of palladium catalysts
with allyltributyltin,3 allyltrimethylsilane4 and an enan-
tioselective version.4 Itsuno has developed a chiral
boron catalyst with triallylborane and a chiral modifier
derived from (−)-norephedrine.5 The formation of the
imine in situ is very desirable given the inherent prob-
lems associated with handling them. In response to this,
one-pot reactions have been reported by Kobayashi
and Akiyama both with scandium triflate as the cata-
lyst.6,7 Whilst these procedures are novel and afford the
desired products, there are still improvements to be
made as some of these methods require up to 10 mol%,
or more, catalyst and sometimes anhydrous conditions.
In addition, some of the reactions can be quite sluggish.
Good yields were obtained for aromatic aldehydes.
Enolisable aldehydes, however, failed to give the
desired product. A 19% yield of the octaldehyde
derived product was obtained but could not be
repeated. It is known, however, that imines with a-pro-
tons undergo side reactions with allyltributylstannane8
and Kobayashi reported that his procedure allowed the
allylation of imines derived from octaldehyde and
hydrocinnamaldehyde.7 The imine derived from
octaldehyde gave 19% of the allylated product at best
and the imine derived from hydrocinnamaldehyde
failed to give any identifiable products.
We carried out our first studies into this reaction using
benzaldehyde and m-toluidine as our two components
with activated (heated to 160°C under high vacuum for
2 h immediately before use) lanthanum triflate at 5
mol% loading. In this initial study, we pre-formed the
imine before reaction. Satisfied that the imine was
The problem with our choice of amine was that the
final products were not synthetically useful. A far better
strategy would be to employ a removable group that
could be cleaved to reveal the homoallylic amine, which
would be far more useful synthetically. Such a group
would be a para-methoxyphenyl group derived from
p-anisidine, that could be cleaved in three steps to
reveal the primary amine.9 Table 2 shows the results of
the allylation of the p-anisidine derived imines.
Keywords: lanthanum triflate; allylation; Brønsted acidity; Lewis
acidity; imines.
* Corresponding author.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)02116-5

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H. C. Aspinall et al. / Tetrahedron Letters 43 (2002) 323–325
Table 1. Unactivated catalyst for in situ imine allylation
Table 2. p-Anisidine derived imine allylations

H. C. Aspinall et al. / Tetrahedron Letters 43 (2002) 323–325
325
OMe
were placed in a 25 mL round bottom flask with a
stirrer bar. MeCN (2 mL) was added and the solution
was stirred until the benzoic acid and the lanthanum
triflate had both dissolved. Freshly distilled aldehyde
(1.22 mmol, 1.0 equiv.) followed by amine (m-toluidine
131 mL, 1.22 mmol, 1.0 equiv. or p-anisidine 0.1501 g,
1.22 mmol, 1.0 equiv.) were added. Allytributylstan-
nane (454 mL, 1.46 mmol, 1.2 equiv.) was then added
and the reaction left to stir, monitoring by TLC. The
mixture was then quenched with 2 M NaOH (2 mL)
and extracted into CH2Cl2 (3×15 mL), the combined
organic layers were dried (MgSO4) and the solvent
removed in vacuo to yield the crude homoallylic amine
product. Purification by flash column chromatography
(typical eluant; 10–30% diethyl ether:petroleum ether)
yielded the product.
OMe
O
1) nBuLi, 0°C to rt
MeO
N
HN
1 hr
O
2)
MeO
Cl
Quant.
CAN 0°C
MeCN: H2O
5 hrs, 33%
O
MeO
NH
NH2
2 eq TMSI
MeCN
o/n, 75%
25% Overall
Scheme 1. Cleavage of p-methoxyphenyl group.
Acknowledgements
Moderate to excellent yields were obtained at low cata-
lyst loading. Cyclohexanecarboxaldehyde, which is eno-
lisable, albeit slowly, gave a moderate yield of the
allylated product. A range of aldehydes are tolerated
including electron rich/depleted aldehydes and tertiary
aldehydes.
We would like to thank EPSRC and Zeneca for finan-
cial support (CASE award to J.S.B.) during this
project.
References
The final step was to cleave the p-methoxyphenyl group
and this was carried out on the benzaldehyde derived
amine product. Conversion to the carbamate proceeded
in quantitative yield but the cleavage of the p-
methoxyphenyl group proceeded in low (33%) yield.
The final step proceeded in good (75%) yield to yield
the primary amine in overall 28% yield9 (Scheme 1).
1. Aspinall, H. C.; Bissett, J. S.; Greeves, N.; Levin, D.
Tetrahedron Lett. 2002, 43, 319–321.
2. Keck, G. E.; Enholm, E. J. J. Org. Chem. 1985, 50,
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So, in summary we have demonstrated that the unacti-
vated lanthanum triflate–benzoic acid catalyst system
can be applied to the one-pot allylation of imines. This
occurs at low catalyst loading, under mild conditions
and with two aromatic amines. The p-methoxyphenyl
group was then cleaved in three steps to yield the
primary amine in overall 25% yield.
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Typical procedure: Lanthanum triflate (0.0141 g, 0.024
mmol, 2 mol%) and benzoic acid (0.149 g, 1.22 mmol)