Convenient Route to 2-(Trialkylstannyl)cyclopropylamines and Their Application in Palladium-Catalyzed Cross-Coupling Reactions

Article abstract of DOI:10.1002/ejoc.200300454

The 2-(trialkylstannyl)-N,N-dialkylcyclopropylamines 3 were obtained by titanium-mediated aminocyclopropanation of tributylvinylstannane with N,N-dialkylformamides in yields of 80-84% and with excellent diastereoselectivities (trans/cis > 45:1). The resulting stannanes could advantageously be applied in Stille cross-coupling reactions with aryl iodides, providing the pure trans-2-aryl-(N,N-dialkylamino)cyclopropanes 8 in yields ranging from 45 to 67% (six examples). The coupling of ethyl (E)-3-iodoacrylate (9) gave ethyl cis-5-(dibenzylamino)cyclopent-2-enecarboxylate (10) as a single diastereomer in 54% yield. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.

Full text of DOI:10.1002/ejoc.200300454

FULL PAPER
Convenient Route to 2-(Trialkylstannyl)cyclopropylamines and Their
Application in Palladium-Catalyzed Cross-Coupling Reactions[‡]
Stefan Wiedemann,[a] Karsten Rauch,[a] Andrei Savchenko,[a] Ilan Marek,[b] and
Armin de Meijere*[a]
Keywords: Cross-coupling / Rearrangement / Small ring systems / Tin / Titanium
The 2-(trialkylstannyl)-N,N-dialkylcyclopropylamines 3 were panes 8 in yields ranging from 45 to 67% (six examples). The
obtained by titanium-mediated aminocyclopropanation of
tributylvinylstannane with N,N-dialkylformamides in yields
coupling of ethyl (E)-3-iodoacrylate (9) gave ethyl cis-5-(di-
benzylamino)cyclopent-2-enecarboxylate (10) as a single
of 80−84% and with excellent diastereoselectivities (trans/cis diastereomer in 54% yield.
Ͼ 45:1). The resulting stannanes could advantageously be
applied in Stille cross-coupling reactions with aryl iodides,
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
providing the pure trans-2-aryl-(N,N-dialkylamino)cyclopro- Germany, 2004)
Introduction
one might expect that a trialkylstannyl group should be at
least as effective in favoring the formation of a trans dia-
stereomer. We therefore tested the preparation of 2-(tri-
alkylstannyl)cyclopropylamines by aminocyclopropanation
with N,N-dialkylformamides of trialkylvinylstannanes via
ligand-exchanged titanacyclopropanes.[6,8]
Among the various cyclopropane derivatives, cyclopro-
pylamines constitute one of the more important classes,
both in view of their roles as key elements in biologically
active compounds[1,2] and as theoretically interesting mol-
ecules.[3] The titanium-mediated reductive cyclopropanation
of N,N-dialkylcarboxamides developed in recent years[4,5]
has significantly improved the accessibility of various cyclo-
propylamines. Except in a few cases, however, this method
has the drawback of yielding 2-substituted cyclopropyl-
amines with only low or moderate degrees of diastereoselec-
tivity. In contrast, the corresponding titanium-mediated
transformation of esters into cyclopropanols yielded trans-
2-substituted (referring to the positions of the hydroxy and
the 2-substituent) derivatives completely diastereoselec-
tively.[5] Complete diastereoselectivity in cyclopropylamine
formation has only been observed in reductive aminocyclo-
propanation of trimethylsilylethylene with N,N-dialkyl-
formamides.[6] Since the electronic effect of a trialkylsilyl
group is in general more important than its steric bulk in
determining the stereochemical outcome of a reaction,[7]
Results and Discussion
In application of the previously developed procedure,[6]
tributylvinylstannane was treated with cyclohexylmagnes-
ium bromide in the presence of methyltriisopropyloxytitan-
ium and an N,N-dialkylformamide 2. After some optimiz-
ation of conditions, the 2-(tributylstannyl)-N,N-dialkylcy-
clopropylamines 3a and 3b were obtained not only in good
yields (80 and 84%, respectively), but also with excellent
trans diastereoselectivities, with diastereomeric excesses Ͼ
95% (Scheme 1).
[‡]
Cyclopropyl Building Blocks for Organic Synthesis, 97. Part 96:
S. I. Kozhushkov, R. Langer, D. S. Yufit, J. A. K. Howard, D.
Demus, K. Miyazawa and A. de Meijere, Eur. J. Org. Chem.,
submitted. Part 95: O. V. Larionov, S. I. Kozhushkov, A. de
Meijere, Synthesis, in press.
[a]
Institut für Organische Chemie der Georg-August-Universität
Göttingen,
Scheme 1. Synthesis of 2-(trialkylstannyl)-N,N-dialkylcyclopropyl-
amines 3
Tammannstrasse 2, 37077 Göttingen, Germany
Fax: (internat.) ϩ 49-(0)551-399475
E-mail: Armin.deMeijere@chemie.uni-goettingen.de
[b]
Department of Chemistry and Institute of Catalysis Science and
This would best be explained by assuming that the inser-
tion of the dialkylformamide carbonyl group occurs prefer-
Technology, Technion Ϫ Israel Institute of Technology,
Technion City, Haifa 32000, Israel
Eur. J. Org. Chem. 2004, 631Ϫ635
DOI: 10.1002/ejoc.200300454
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
631

S. Wiedemann, K. Rauch, A. Savchenko, I. Marek, A. de Meijere
FULL PAPER
entially, for electronic reasons, into the more highly substi-
tuted titanium-carbon bond of the titanacyclopropane
intermediate 4 (Scheme 2, mode b) when R1 is a trialkyl-
stannyl (or a trialkylsilyl) group, resulting in an oxatitana-
cyclopentane intermediate 5b. This would open up to give
an iminium-titanium oxide zwitterion 6b, in which R1 is
adjacent to the iminium ion moiety. In this situation, the
stereochemical information on the substituted carbon
would translate more efficiently onto the stereogenic center
newly formed upon ring closure to the 2-substituted cyclo-
propylamine 7 (Scheme 2). It is obvious that in the ring
closure of the corresponding zwitterion 6a, formed via 5a
after insertion of the formamide into the least substituted
TiϪC bond in 4 (mode a), the 1,3-relationship of the old
and the newly formed stereogenic center should result in
weaker stereocontrol. However, in view of the fact that
titanacyclopropenes from alkynyltributylstannanes undergo
insertion of aldehydes only into the titanium-carbon bond
not bearing the tin substituent[9] (corresponding to mode a
in Scheme 2), this explanation becomes less probable. It is
Scheme 3. Cross coupling of cyclopropylstannane 3a with phenyl
iodide; for details see Table 1
By modifying the conditions, especially by switching to
palladium acetate as the catalyst precursor and optimizing
the temperature, the yield could be raised to 67% (Entry 3
in Table 1). A temperature of 80 °C turned out to be the
optimum, any further increase resulting in destannylation
as a competing side reaction.
Table 1. Palladium-catalyzed cross coupling of cyclopropylstan-
nane 3a with phenyl iodide (see Scheme 3). A: [Pd2dba3]·CHCl3 (10
mol %), AsPh3 (15 mol %), CuI (5 mol %), LiCl (3 equiv.), DMF,
12 h; B: as A, but with Pd(OAc)2 (5 mol %); C: as B, but in N-
also known that silyl-substituted titanacyclopropane inter- methylpyrrolidinone (NMP)
mediates react with aldehydes only according to insertion
mode a.[10] After all, the high diastereoselectivity observed
in the conversion of N,N-dialkylformamides with vinylstan-
nanes to 2-stannylcyclopropylamines may simply be due to
the steric bulk of the trialkylstannyl group. A control
experiment with 3,3-dimethylbut-1-ene (tert-butylethene)
also gave only trans-N,N-dibenzyl-2-tert-butylcyclopropyl-
amine, but in poor yield (19%) and an impure state.
Entry
Conditions
Temperature
[°C]
Yield
(%)
1
2
3
4
5
6
A
A
B
B
B
C
65
80
80
100
120
80
48
56
67
48
19
13
Various aryl iodides were coupled to 3a and 3b
(Scheme 4) according to the optimized procedure. While
meta- and para-substituted aryl iodides gave the corre-
sponding 2-arylcyclopropylamines in moderate to good
yields, ortho-iodotoluene failed to furnish any coupling
product.
Scheme 2
Cyclopropylstannanes, although not amino-substituted
ones, have previously been used as versatile building blocks
for the construction of other cyclopropane derivatives; ex-
amples include palladium-catalyzed oxidative homocoup-
ling to yield bicyclopropyl derivatives[11] and destannylative
transformation,[12] as well as transmetallations with sub-
sequent electrophilic substitution[13] or cross-coupling reac-
tions.[14] A few examples of direct palladium-catalyzed
cross-coupling reactions of cyclopropylstannanes have also
been reported.[15,16] To test this possibility with the readily
available aminocyclopropylstannanes 3, the dibenzylamino
derivative 3a was treated with phenyl iodide under typical
conditions for the cross coupling of aryl and vinylstan-
nanes. The initial results were disappointing, but the cross-
coupling product 8aa was eventually obtained in 48% yield
Scheme 4. Palladium-catalyzed cross-couplings of 2-(trialkyl-
stannyl)-N,N-dialkylcyclopropylamines 3 with various aryl iodides
under optimized conditions B (see Table 1)
Surprisingly, ethyl trans-3-iodoacrylate (9) did not pro-
through the use of a procedure previously developed by vide the expected 3-(aminocyclopropyl)acrylate 11, but in-
Farina et al.[17] (Scheme 3 and Table 1, conditions A).
stead gave ethyl cis-5-(dibenzylamino)cyclopent-2-enecar-
632
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Eur. J. Org. Chem. 2004, 631Ϫ635

Convenient Route to 2-(Trialkylstannyl)cyclopropylamines
FULL PAPER
titanium (4.8 g, 20 mmol) were added to
a solution of
boxylate (10) as a single diastereomer. The same product
was obtained with ethyl cis-3-iodoacrylate, but in very low
yield (5%). Most probably, the coupling product 11 is in-
itially formed, but, being a donor-acceptor-substituted
cyclopropane derivative,[18] undergoes rapid ring-opening to
the zwitterionic intermediate 12 under the conditions em-
ployed. Because of the attractive interaction between the
termini in this iminium enolate, the ring-closure places the
two substituents on the same side of the ring.
dibenzylformamide (4.5 g, 20 mmol) in THF (20 mL). A solution
of cyclohexylmagnesium bromide (0.8  in THF, 31 mL, 25 mmol)
was then added carefully. The resulting dark mixture was stirred at
ambient temperature for 8 h. The reaction was quenched by careful
addition of H2O (2 mL), and the mixture was filtered. The residue
was washed with diethyl ether (3 ϫ 10 mL), and the two layers were
separated. The aqueous phase was extracted with diethyl ether (2
ϫ 10 mL), and the combined organic extracts were dried with an-
hydrous Na2SO4 and concentrated under reduced pressure. The
residue was purified by column chromatography by elution with
pentane/diethyl ether 100:1, affording two fractions.
Fraction I (Rf ϭ 0.76): cis-N,N-dibenzyl-2-(tributylstannyl)cyclo-
propylamine (60 mg, 1%) as a colorless oil. IR (film): ν˜ ϭ 3081
cmϪ1, 3062, 3028, 2955, 2922, 2870, 2853, 1494, 1451, 747, 698. 1H
3
3
NMR (250 MHz, CDCl3): δ ϭ 0.03 (ddd, J ϭ 7.0, 2J ϭ 8.1, J ϭ
3
3
2
10.4 Hz, 1 H, 3-H), 0.27 (ddd, J ϭ 3.7, J ϭ 4.0, J ϭ 8.1 Hz, 1
3
3
3
H, 3-H), 0.79 (ddd, J ϭ 4.0, J ϭ 6.6, J ϭ 10.4 Hz, 1 H, 2-H),
3
3
0.89 (t, J ϭ 7.0 Hz, 9 H, 4Ј-H), 0.91 (t, J ϭ 5.8 Hz, 6 H, 1Ј-H),
1.31 (tq, 3J ϭ 7.0, 3J ϭ 7.9 Hz, 6 H, 3Ј-H), 1.50 (tt, 3J ϭ 5.8, 3J ϭ
3
3
3
7.9 Hz, 6 H, 2Ј-H), 2.09 (ddd, J ϭ 3.7, J ϭ 6.6, J ϭ 7.0 Hz, 1
H, 1-H), 3.55 (AB, d, 2J ϭ 13.7 Hz, 2 H, NCH2), 3.75 (AB, d, 2J ϭ
13.7 Hz, 2 H, NCH2), 7.22Ϫ7.39 (m, 10 H, Ph-H) ppm. 13C NMR
(62.9 MHz, CDCl3, additional DEPT): δ ϭ 9.9 (ϩ, 3 C, C-4Ј), 11.8
(Ϫ, 1 C, C-3), 13.7 (Ϫ, 3 C, C-1Ј), 14.1 (ϩ, 1 C, C-2), 27.5 (Ϫ, 3
C, C-3Ј), 29.2 (Ϫ, 3 C, C-2Ј), 40.2 (ϩ, 1 C, C-1), 57.0 (Ϫ, 2 C,
NCH2), 126.7 (ϩ, 2 C, PhϪC), 127.9 (ϩ, 4 C, PhϪC), 129.6 (ϩ, 4
C, PhϪC), 137.9 (Cquat., 2 C, PhϪC) ppm. MS (CI, 70 eV): m/z
(%) ϭ 528 (100) [Mϩ ϩ 1], 438 (14), 308 (10), 238 (25), 198 (14),
163 (5), 146 (48), 106 (15).
Scheme 5. Cross coupling of N,N-dibenzyl-2-(tributylstannyl)cyclo-
propylamine (3a) with ethyl trans-3-iodoacrylate (9) and sub-
sequent rearrangement to yield ethyl cis-5-(dibenzylamino)cyclo-
pent-2-enecarboxylate (10)
This coupling-rearrangement sequence constitutes a dia-
stereoselective synthesis of an interesting β-aminocyclopen-
tenecarboxylic acid in a protected form. The facility of this
stereoselective approach to a synthetically useful cyclopen-
tene derivative warrants further investigations into coupling
reactions of the readily available aminocyclopropylstan-
nanes, with, for example, various functionally substituted
iodoalkenes[14a] and β-iodo-substituted α,β-unsaturated
carbonyl compounds.[14b]
Fraction II (Rf ϭ 0.32): compound 3a (4.89 g, 8.0 mmol, 92%) as
a colorless oil. IR (film): ν˜ ϭ 3085 cmϪ1, 3062, 3027, 2957, 2925,
2871, 2852, 1494, 1454, 1029, 747, 698. 1H NMR (250 MHz,
3
2
3
CDCl3): δ ϭ Ϫ0.03 (ddd, J ϭ 4.9, J ϭ 7.6, J ϭ 10.4 Hz, 1 H,
3
3
2
3-H), 0.40 (ddd, J ϭ 4.0, J ϭ 5.8, J ϭ 7.6 Hz, 1 H, 3-H), 0.63
(ddd, 3J ϭ 3.4, 3J ϭ 4.0, 3J ϭ 10.4 Hz, 1 H, 2-H), 0.76 (t, 3J ϭ
3
3
7.9 Hz, 6 H, 1Ј-H), 0.89 (t, J ϭ 7.0 Hz, 9 H, 4Ј-H), 1.30 (tt, J ϭ
3
3
3
6.7, J ϭ 7.9 Hz, 6 H, 2Ј-H), 1.44 (tq, J ϭ 6.7, J ϭ 7.0 Hz, 6 H,
3
3
3
3Ј-H), 1.87 (ddd, J ϭ 3.4, J ϭ 4.9, J ϭ 5.8 Hz, 1 H, 1-H), 3.67
Experimental Section
2
2
(AB, d, J ϭ 13.7 Hz, 2 H, NCH2), 3.72 (AB, d, J ϭ 13.7 Hz, 2
H, NCH2), 7.22Ϫ7.34 (m, 10 H, Ph-H) ppm. 13C NMR (62.9 MHz,
CDCl3, additional DEPT): δ ϭ 3.6 (ϩ, 1 C, C-2), 8.7 (Ϫ, 3 C, C-
1Ј), 12.2 (Ϫ, 1 C, C-3), 13.7 (ϩ, 3 C, C-4Ј), 27.4 (Ϫ, 3 C, C-2Ј),
29.3 (Ϫ, 3 C, C-3Ј), 41.1 (ϩ, 1 C, C-1), 58.7 (Ϫ, 2 C, NCH2), 126.7
(ϩ, 2 C, PhϪC), 127.9 (ϩ, 4 C, PhϪC), 129.3 (ϩ, 4 C, PhϪC),
139.1 (Cquat., 2 C, PhϪC) ppm. MS (CI, 70 eV): m/z (%) ϭ 528
(100) [Mϩ ϩ 1], 438 (5), 308 (10), 236 (55), 198 (3), 146 (15).
C29H45NSn (526.4): calcd. C 66.17, H 8.62, N 2.66; found C 65.87,
H 8.32, N 2.58.
General Remarks: All chemicals were used as commercially avail-
able. All reactions were performed in anhydrous solvents under N2.
Ethereal solvents were dried under N2 with sodium. Reactions were
monitored by thin-layer chromatography on silica gel plates
(MachereyϪNagel SIL G/UV254). The chromatograms were viewed
under UV light or by spraying with ninhydrin. Silica gel 60
(0.063Ϫ0.200 mm, 230Ϫ400 mesh) obtained from E. Merck,
Darmstadt (VWR Intl) was used for column chromatography. El-
uents were distilled before use. NMR spectra were recorded with a
Bruker AM 250 instrument at 250 MHz (1H) and at 62.9 MHz
(13C) in CDCl3. Chemical shifts δ are reported in ppm with CHCl3
(1H, 7.26 ppm) and CDCl3 (13C, 77.0 ppm) as internal standards.
13C NMR spectral assignments are supported by DEPT analysis,
‘‘ϩ’’ designates CH or CH3, ‘‘Ϫ’’ designates CH2, and Cquat. stands
for quaternary carbon atoms. Infrared spectra were recorded with
a Bruker IFS 66 (FT-IR) instrument. Mass spectra were obtained
with Varian MAT CH 7, MAT 731, and Varian MAT 311 A (for
HRMS) instruments. High-resolution mass spectra (HRMS) were
obtained by use of a preselected-ion peak matching at R ϭ 10000
to be within Ϯ 2 ppm of the exact mass.
trans-N,N-Dimethyl-2-(tributylstannyl)cyclopropylamine (3b): Tri-
butylvinylstannane (3.2 g, 10 mmol) and then methyltriisopropyl-
oxytitanium (4.8 g, 20 mmol) were added to a solution of dimeth-
ylformamide (1.5 g, 21 mmol) in THF (20 mL). A solution of
cyclohexylmagnesium bromide (0.8  in THF, 31 mL, 25 mmol)
was then added carefully. The resulting dark mixture was stirred at
ambient temperature for 8 h. The reaction was quenched by careful
addition of H2O (2 mL), and the mixture was filtered. The residue
was washed with diethyl ether (3 ϫ 10 mL), and the two layers were
separated. The aqueous phase was extracted with diethyl ether (2
ϫ 10 mL), and the combined organic extracts were dried with an-
hydrous Na2SO4 and concentrated under reduced pressure. The
residue was purified by column chromatography, eluting with pen-
N,N-Dibenzyl-2-(tributylstannyl)cyclopropylamine (3a): Tributyl-
vinylstannane (3.2 g, 10 mmol) and then methyltriisopropyloxy-
Eur. J. Org. Chem. 2004, 631Ϫ635
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 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
633

S. Wiedemann, K. Rauch, A. Savchenko, I. Marek, A. de Meijere
trans-N,N-Dibenzyl-2-(4Ј-methylphenyl)cyclopropylamine (8ac):
FULL PAPER
tane/diethyl ether 10:1 (Rf ϭ 0.14), to afford 3b (3.34 g, 88%) as a
colorless oil. IR (film): ν˜ ϭ 3057 cmϪ1, 2925, 2812, 2766, 1457, Treatment of 3a (526 mg, 1 mmol) and 4-iodotoluene (436 mg,
1363, 1206, 1163, 921, 887, 754. 1H NMR (250 MHz, CDCl3): δ ϭ 2 mmol) according to the GP gave 8ac (210 mg, 65%) as a colorless
Ϫ0.08 (ddd, 3J ϭ 5.2, 2J ϭ 7.6, 3J ϭ 11.3 Hz, 1 H, 3-H), 0.45 (ddd, solid after column chromatography (dichloromethane, Rf ϭ 0.64),
3J ϭ 4.0, 3J ϭ 6.1, J ϭ 7.6 Hz, 1 H, 3-H), 0.68 (ddd, J ϭ 3.7,
m.p. 47 °C. IR (film): ν˜ ϭ 3061 cmϪ1, 3027, 2922, 2801, 1517, 1453,
1 2
2
3
3
3
3J ϭ 4.0, J ϭ 11.3 Hz, 1 H, 2-H), 0.79 (t, J ϭ 7.6 Hz, 6 H, 1Ј-
1120, 749, 698. H NMR (250 MHz, CDCl3): δ ϭ 0.94 (ddd, J ϭ
3
H), 0.88 (t, 3J ϭ 7.0 Hz, 9 H, 4Ј-H), 1.30 (tt, 3J ϭ 7.6, 3J ϭ 7.6 Hz, 4.3, 3J ϭ 5.8, 3J ϭ 7.5 Hz, 1 H, 3-H), 1.02 (ddd, 2J ϭ 4.3, J ϭ
3
3
3
3
6 H, 2Ј-H), 1.49 (tq, J ϭ 7.0, J ϭ 7.6 Hz, 6 H, 3Ј-H), 1.55 (ddd, 4.5, 3J ϭ 9.1 Hz, 1 H, 3-H), 1.81 (ddd, J ϭ 3.1, 3J ϭ 5.8, J ϭ
3J ϭ 3.7, J ϭ 5.2, 3J ϭ 6.1 Hz, 1 H, 1-H), 2.34 [s, 6 H, N(CH3)2].
9.1 Hz, 1 H, 1-H), 2.02 (ddd, 3J ϭ 3.1, 3J ϭ 4.5, 3J ϭ 7.5 Hz, 1 H,
3
13C NMR (62.9 MHz, CDCl3, additional DEPT): δ ϭ 2.5 (ϩ, 1 C,
2-H), 2.31 (s, 3 H, PhϪCH3), 3.67 (AB, d, 2J ϭ 13.5 Hz, 2 H,
2
C-2), 8.6 (ϩ, 3 C, C-1Ј), 11.5 (Ϫ, 1 C, C-3), 13.7 (Ϫ, 3 C, C-4Ј), NCH2), 3.77 (AB, d, J ϭ 13.5 Hz, 2 H, NCH2), 6.70Ϫ6.73 (m, 2
27.4 (Ϫ, 3 C, C-2Ј), 29.1 (Ϫ, 3 C, C-3Ј), 44.3 (ϩ, 1 C, C-1), 45.4
H, Ph-H), 7.00Ϫ7.04 (m, 2 H, Ph-H), 7.26Ϫ7.32 (m, 10 H, Ph-H)
(ϩ, 2 C, NCH3). MS (CI, 70 eV): m/z (%) ϭ 376/374 (100/77) [Mϩ], ppm. 13C NMR (62.9 MHz, CDCl3, additional DEPT): δ ϭ 17.4
308 (8), 200 (3), 100 (3), 84 (16). C17H37NSn (374.2): calcd. C 54.57, (Ϫ, 1 C, C-3), 21.0 (ϩ, 1 C, PhϪCH3), 26.0 (ϩ, 1 C, C-2), 47.4 (ϩ,
H, 9.97, N 3.74; found C 54.32, H 9.69, N 3.70.
1 C, C-1), 58.4 (Ϫ, 2 C, NCH2), 125.7 (ϩ, 2 C, PhϪC), 126.8 (ϩ,
2 C, PhϪC), 128.1 (ϩ, 2 C, PhϪC), 128.7 (ϩ, 4 C, PhϪC), 129.4
(ϩ, 4 C, PhϪC), 134.8 (Cquat., 1 C, PhϪC), 138.7 (Cquat., 2 C,
PhϪC), 139.0 (Cquat., 1 C, PhϪC) ppm. MS (EI, 70 eV): m/z (%) ϭ
327 (14) [Mϩ], 276 (5), 236 (65), 222 (22), 131 (15), 105 (53), 91
(100), 65 (6). C24H25N: 327.1987 (correct HRMS). C24H25N
(327.4): calcd. C 88.03, H 7.69, N 4.28; found C 88.11, H 7.43,
N 4.21.
General Procedure for the Stille Coupling of 2-(Trialkylstannyl)cy-
clopropylamines
3 (GP): A solution of Pd(OAc)2 (11 mg,
0.05 mmol, 5 mol %), CuI (10 mg, 53 µmol, 5 mol %), triphenylar-
sane (45 mg, 0.15 mmol, 15 mol %), lithium chloride (128 mg,
3 mmol), the cyclopropylstannane (1 mmol), and the aryl iodide
(2 mmol) in DMF (10 mL) was placed in a Pyrex bottle and deoxy-
genated by passage of a stream of nitrogen through the solution
for 30 min. The bottle was then carefully sealed and heated at 80
°C for 12 h. The mixture was poured into an aqueous ammonia
solution (10%, 20 mL) and extracted with diethyl ether (3 ϫ
50 mL). The combined organic extracts were dried with anhydrous
Na2SO4 and concentrated under reduced pressure. The residue was
purified by column chromatography.
trans-N,N-Dimethyl-2-(4Ј-methylphenyl)cyclopropylamine
(8bc):
Treatment of 3b (375 mg, 1 mmol) and 4-iodotoluene (436 mg,
2 mmol) according to the GP gave 8bc (110 mg, 63%) as a colorless
oil after column chromatography (diethyl ether, Rf ϭ 0.38). IR
(film): ν˜ ϭ 3061 cmϪ1, 1517, 1453, 1120, 749, 698. 1H NMR
(250 MHz, CDCl3): δ ϭ 0.93 (ddd, 2J ϭ 4.5, 3J ϭ 5.8, 3J ϭ 7.2 Hz,
3
2
3
1 H, 3-H), 1.08 (ddd, J ϭ 4.3, J ϭ 4.5, J ϭ 9.4 Hz, 1 H, 3-H),
trans-N,N-Dibenzyl-2-phenylcyclopropylamine (8aa): Treatment of
3a (526 mg, 1 mmol) and iodobenzene (408 mg, 2 mmol) according
to the GP gave 8aa (210 mg, 67%) as a colorless solid after column
chromatography (dichloromethane, Rf ϭ 0.50), m.p. 49 °C. 1H
3
3
3
1.77 (ddd, J ϭ 3.2, J ϭ 4.3, J ϭ 7.2 Hz, 1 H, 2-H), 2.02 (ddd,
3J ϭ 3.2, 3J ϭ 5.8, 3J ϭ 9.4 Hz, 1 H, 1-H), 2.31 (s, 3 H, PhϪCH3),
2.39 (s, 6 H, NCH3), 6.95Ϫ6.99 (m, 2 H, Ph-H), 7.05Ϫ7.11 (m, 2
H, Ph-H) ppm. 13C NMR (62.9 MHz, CDCl3, additional DEPT):
δ ϭ 17.0 (Ϫ, 1 C, C-3), 20.9 (ϩ, 1 C, PhϪCH3), 24.8 (ϩ, 1 C, C-
2), 45.0 (ϩ, 2 C, NCH3), 50.0 (ϩ, 1 C, C-1), 126.0 (ϩ, 2 C, PhϪC),
128.9 (ϩ, 2 C, PhϪC), 135.1 (Cquat., 1 C, PhϪC), 139.0 (Cquat., 1
C, PhϪC) ppm. MS (EI, 70 eV): m/z (%) ϭ 175 (57) [Mϩ], 160
(20), 131 (20), 105 (25), 84 (36), 70 (100). C12H17N (175.3): calcd.
C 82.23, H 9.78, N 7.99; found C 82.02, H 9.68, N 8.06.
2
3
NMR (250 MHz, CDCl3): δ ϭ 0.97 (ddd, J ϭ 4.3, 3J ϭ 6.0, J ϭ
7.5 Hz, 1 H, 3-H), 1.05 (ddd, 2J ϭ 4.3, 3J ϭ 4.5, 3J ϭ 9.2 Hz, 1 H,
3
3
3
3-H), 1.82 (ddd, J ϭ 3.2, J ϭ 6.0, J ϭ 9.2 Hz, 1 H, 1-H), 2.04
(ddd, 3J ϭ 3.2, 3J ϭ 4.5, 3J ϭ 7.5 Hz, 1 H, 2-H), 3.67 (AB, d, 2J ϭ
13.5 Hz, 2 H, NCH2), 3.79 (AB, d, 2J ϭ 13.5 Hz, 2 H, NCH2),
6.70Ϫ6.87 (m, 2 H, Ph-H), 7.24Ϫ7.47 (m, 13 H, Ph-H) ppm. 13C
NMR (62.9 MHz, CDCl3, additional DEPT): δ ϭ 17.6 (Ϫ, 1 C, C-
3), 26.4 (ϩ, 1 C, C-2), 47.6 (ϩ, 1 C, C-1), 58.4 (Ϫ, 2 C, NCH2),
125.3 (ϩ, 2 C, PhϪC), 125.7 (ϩ, 1 C, PhϪC), 126.9 (ϩ, 4 C,
PhϪC), 128.0 (ϩ, 2 C, PhϪC), 128.1 (ϩ, 4 C, PhϪC), 129.4 (ϩ, 2
C, PhϪC), 138.7 (Cquat., 2 C, PhϪC), 142.1 (Cquat., 1 C, PhϪC)
ppm. C23H23N (313.4): calcd. C 88.14, H 7.40, N 4.47; found C
87.94, H 7.17, N 4.32.
trans-N,N-Dibenzyl-2-(3Ј,5Ј-di-tert-butylphenyl)cyclopropylamine
(8ad): Treatment of 3a (526 mg, 1 mmol) and 3,5-di-tert-butyliodo-
benzene (632 mg, 2 mmol) according to the GP gave 8ad (270 mg,
63%) as a colorless solid after column chromatography (diethyl
ether/pentane, 1:10, Rf ϭ 0.74), m.p. 72 °C. IR (KBr): ν˜ ϭ 3063
cmϪ1, 3028, 2964, 2866, 1599, 1453, 1362, 1248, 1121, 748, 698. 1H
3
trans-N,N-Dimethyl-2-phenylcyclopropylamine (8ba): Treatment of
3b (375 mg, 1 mmol) and iodobenzene (408 mg, 2 mmol) according
to the GP gave 8ba (95 mg, 59%) as a colorless oil after column
NMR (250 MHz, CDCl3): δ ϭ 0.97 (ddd, 2J ϭ 4.3, 3J ϭ 5.8, J ϭ
7.3 Hz, 1 H, 3-H), 1.04 (ddd, 2J ϭ 4.3, 3J ϭ 4.3, 3J ϭ 9.1 Hz, 1 H,
3
3
3
3-H), 1.34 [s, 18 H, C(CH3)3], 1.91 (ddd, J ϭ 3.6, J ϭ 5.8, J ϭ
chromatography (diethyl ether, Rf ϭ 0.30). IR (film): ν˜
ϭ
1
9.1 Hz, 1 H, 1-H), 2.14 (ddd, 3J ϭ 3.6, 3J ϭ 4.3, 3J ϭ 7.3 Hz, 1 H,
2-H), 3.67 (AB, d, J ϭ 13.5 Hz, 2 H, NCH2), 3.77 (AB, d, J ϭ
3060 cmϪ1, 2939, 2815, 2771, 1499, 1453, 1213, 783, 742, 697. H
2
2
2
3
NMR (250 MHz, CDCl3): δ ϭ 0.96 (ddd, J ϭ 4.4, 3J ϭ 5.8, J ϭ 13.5 Hz, 2 H, NCH2), 6.74 (d, 4J ϭ 1.8 Hz, 2 H, Ph-H), 7.24Ϫ7.36
6.9 Hz, 1 H, 3-H), 1.11 (ddd, 3J ϭ 4.3, 2J ϭ 4.4, 3J ϭ 9.3 Hz, 1 H,
(m, 11 H, Ph-H) ppm. 13C NMR (62.9 MHz, CDCl3, additional
DEPT): δ ϭ 17.7 (Ϫ, 1 C, C-3), 26.6 (ϩ, 1 C, C-2), 31.5 [ϩ, 6 C,
3
3
3
3-H), 1.81 (ddd, J ϭ 3.2, J ϭ 4.3, J ϭ 6.9 Hz, 1 H, 2-H), 1.98
(ddd, 3J ϭ 3.2, 3J ϭ 5.8, 3J ϭ 9.3 Hz, 1 H, 1-H), 2.40 (s, 6 H, C(CH3)3], 34.8 [Cquat., 2 C, C(CH3)3], 47.4 (ϩ, 1 C, C-1), 58.5 (Ϫ,
NCH3), 7.04Ϫ7.30 (m, 5 H, Ph-H) ppm. 13C NMR (62.9 MHz, 2 C, NCH2), 119.7 (ϩ, 1 C, PhϪC), 120.1 (ϩ, 2 C, PhϪC), 126.8
CDCl3, additional DEPT): δ ϭ 17.2 (Ϫ, 1 C, C-3), 25.2 (ϩ, 1 C,
C-2), 45.0 (ϩ, 2 C, NCH3), 50.2 (ϩ, 1 C, C-1), 125.6 (ϩ, 1 C, 139.0 (Cquat., 2 C, PhϪC), 141.0 (Cquat., 2 C, PhϪC), 150.4 (Cquat.
PhϪC), 126.0 (ϩ, 2 C, PhϪC), 128.2 (ϩ, 2 C, PhϪC), 142.1 (Cquat.
1 C, PhϪC) ppm. MS (EI, 70 eV): m/z (%) ϭ 425 (22) [Mϩ], 391
(ϩ, 2 C, PhϪC), 128.1 (ϩ, 4 C, PhϪC), 129.4 (ϩ, 4 C, PhϪC),
,
,
1 C, PhϪC) ppm. MS (EI, 70 eV): m/z (%) ϭ 161 (100), 146 (20), (4), 334 (40), 222 (25), 210 (43), 146 (21), 91 (100), 57 (14).
117 (21), 84 (39), 70 (97). C11H15N (161.2): calcd. C 81.94, H 9.38, C31H39N: 425.3082 (correct HRMS). C31H39N (425.7): calcd. C
N 8.69; found C 81.62, H 9.58, N 8.55.
87.47, H 9.24, N 3.29; found C 87.53, H 8.92, N 3.20.
634
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2004, 631Ϫ635

Convenient Route to 2-(Trialkylstannyl)cyclopropylamines
FULL PAPER
2.5, J ϭ 6.0 Hz, 1 H, 3-H), 5.90 (dddd, J ϭ 2.0, J ϭ 2.1, J ϭ
3
4
3
4
trans-N,N-Dibenzyl-2-(4Ј-methoxycarbonylphenyl)cyclopropylamine
(8ae): Treatment of 3a (526 mg, 1 mmol) and methyl 4-iodobenzo- 2.4, J ϭ 6.0 Hz, 1 H, 2-H), 7.22Ϫ7.41 (m, 10 H, Ph-H) ppm. 13C
3
ate (524 mg, 2 mmol) according to the GP gave 8ae (167 mg, 45%)
NMR (62.9 MHz, CDCl3, additional DEPT): δ ϭ 14.2 (ϩ, 1 C,
as a colorless solid after column chromatography (pentane/diethyl CH3), 35.5 (Ϫ, 1 C, C-4), 51.8 (ϩ, 1 C, C-1), 53.9 (Ϫ, 2 C, NCH2),
ether, 10:1, Rf ϭ 0.34), m.p. 85 °C. IR (KBr): ν˜ ϭ 3023 cmϪ1
2949, 2918, 1723, 1609, 1440, 1281, 1183, 1117, 751, 707. 1H NMR
,
60.7 (Ϫ, 1 C, OCH2), 62.2 (ϩ, 1 C, C-5), 126.8 (ϩ, 2 C, PhϪC),
127.9 (ϩ, 1 C, C-3), 128.2 (ϩ, 4 C, PhϪC), 128.6 (ϩ, 4 C, PhϪC),
(250 MHz, CDCl3): δ ϭ 0.90 (ddd, 2J ϭ 5.0, 3J ϭ 5.8, 3J ϭ 6.9 Hz, 133.1 (ϩ, 1 C, C-2), 139.7 (Cquat., 2 C, PhϪC), 174.7 (Cquat., 1 C,
3
2
3
1 H, 3-H), 1.12 (ddd, J ϭ 4.4, J ϭ 5.0, J ϭ 9.4 Hz, 1 H, 3-H), CO) ppm. MS (EI, 70 eV): m/z (%) ϭ 335 (60) [Mϩ], 306 (46), 262
3
3
3
1.75 (ddd, J ϭ 3.1, J ϭ 5.8, J ϭ 9.4 Hz, 1 H, 1-H), 2.10 (ddd,
(36), 244 (31), 222 (4), 170 (6), 91 (100), 65 (6). C22H25NO2:
3J ϭ 3.1, 3J ϭ 4.4, 3J ϭ 6.9 Hz, 1 H, 2-H), 3.54 (AB, d, 2J ϭ 335.1885 (correct HRMS).
2
9.2 Hz, 2 H, NCH2), 3.65 (AB, d, J ϭ 9.2 Hz, 2 H, NCH2), 3.91
(s, 3 H, OCH3), 6.72Ϫ6.80 (m, 2 H, Ph-H), 7.21Ϫ7.39 (m, 10 H,
Ph-H), 7.94Ϫ7.98 (m, 2 H, Ph-H) ppm. 13C NMR (62.9 MHz,
CDCl3, additional DEPT): δ ϭ 16.3 (Ϫ, 1 C, C-3), 25.8 (ϩ, 1 C,
Acknowledgments
This work was supported by the Niedersächsisches Ministerium für
C-2), 47.1 (ϩ, 1 C, C-1), 51.8 (ϩ, 1 C, OCH3), 58.4 (Ϫ, 2 C,
NCH2), 113.5 (ϩ, 2 C, PhϪC), 126.8 (ϩ, 2 C, PhϪC), 126.9 (ϩ, 2
C, PhϪC), 128.1 (ϩ, 4 C, PhϪC), 129.4 (ϩ, 4 C, PhϪC), 134.1
(Cquat., 2 C, PhϪC), 138.7 (Cquat., 1 C, PhϪC), 138.7 (Cquat., 1 C,
PhϪC), 166.3 (Cquat., 1 C, COO) ppm. MS (EI, 70 eV): m/z (%) ϭ
371 (9) [Mϩ], 280 (90), 222 (15), 175 (10), 149 (20), 106 (10), 91
(100), 65 (6). C25H25NO2 (371.5): calcd. C 80.83, H 6.78, N 3.77;
found C 81.10, H 6.70, N 3.59.
Wissenschaft und Kunst and the Fonds der Chemischen Industrie.
The authors are indebted to Dr. Burkhard Knieriem, Göttingen,
for his careful proofreading of the final manuscript.
[1]
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A. de Meijere, V. Chaplinski, F. Gerson, P. Merstetter, E.
[3]
trans-N,N-Dibenzyl-2-(4Ј-methoxyphenyl)cyclopropylamine
(8af):
Haselbach, J. Org. Chem. 1999, 64, 6951Ϫ6959.
Treatment of 3a (526 mg, 1 mmol) and 4-iodoanisole (468 mg,
2 mmol) according to the GP gave 8af (167 mg, 49%) as a colorless
oil after column chromatography (dichloromethane, Rf ϭ 0.72). IR
(film): ν˜ ϭ 3062 cmϪ1, 3028, 3002, 2923, 1833, 1611, 1515, 1247,
[4]
A. de Meijere, S. I. Kozhushkov, A. I. Savchenko, in Titanium
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Review: O. G. Kulinkovich, A. de Meijere, Chem. Rev. 2000,
100, 2789Ϫ2834.
A. de Meijere, C. M. Williams, A. Kourdioukov, S. V. Sviridov,
V. Chaplinski, M. Kordes, A. I. Savchenko, C. Stratmann, M.
[5]
1
1177, 1038, 826, 749, 698. H NMR (250 MHz, CDCl3): δ ϭ 0.94
2
3
3
3
(ddd, J ϭ 5.1, J ϭ 5.9, J ϭ 6.7 Hz, 1 H, 3-H), 1.02 (ddd, J ϭ
[6]
4.4, 2J ϭ 5.1, 3J ϭ 9.4 Hz, 1 H, 3-H), 1.81 (ddd, 3J ϭ 3.2, 3J ϭ
5.9, 3J ϭ 9.4 Hz, 1 H, 1-H), 2.02 (ddd, J ϭ 3.2, 3J ϭ 4.4, J ϭ
3
3
Noltemeyer, Chem. Eur. J. 2002, 8, 3789Ϫ3801.
2
[7]
6.7 Hz, 1 H, 2-H), 3.67 (AB, d, J ϭ 13.5 Hz, 2 H, NCH2), 3.79 (s,
3 H, OCH3), 3.79 (AB, d, J ϭ 13.5 Hz, 2 H, NCH2), 6.74Ϫ6.78
I. Fleming, A. Barbero, D. Walter, Chem. Rev. 1997, 97,
2
2063Ϫ2192.
[8]
(m, 4 H, Ph-H), 7.23Ϫ7.36 (m, 10 H, Ph-H) ppm. 13C NMR
(62.9 MHz, CDCl3, additional DEPT): δ ϭ 17.0 (Ϫ, 1 C, C-3), 25.7
(ϩ, 1 C, C-2), 47.3 (ϩ, 1 C, C-1), 55.3 (ϩ, 1 C, OCH3), 58.4 (Ϫ, 2
C, NCH2), 113.5 (ϩ, 2 C, PhϪC), 126.8 (ϩ, 2 C, PhϪC), 126.9
(ϩ, 2 C, PhϪC), 128.1 (ϩ, 4 C, PhϪC), 129.4 (ϩ, 4 C, PhϪC),
For the use of vinylstannanes in the synthesis of vinylcyclopro-
panols see: K. Lee, S. Kim, J. K. Cha, J. Org. Chem. 1998,
63, 9135Ϫ9138.
[9]
V. Launay, I. Beaudet, J.-P. Quintard, Synlett 1997, 821Ϫ823.
[10]
R. Mizojiri, H. Urabe, F. Sato, J. Org. Chem. 2000, 65,
6217Ϫ6222.
[11]
134.1 (Cquat., 2 C, PhϪC), 138.7 (Cquat., 1 C, PhϪC), 138.7 (Cquat.
,
T. Itoh, S. Emoto, M. Kondo, Tetrahedron 1998, 54,
5225Ϫ5232.
M. Pohmakotr, A. Takampon, Tetrahedron Lett. 1996, 37,
4585Ϫ4588.
1 C, PhϪC) ppm. MS (EI, 70 eV): m/z (%) ϭ 343 (6) [Mϩ], 252
(27), 222 (13), 186 (10), 121 (68), 91 (100), 65 (15), 43 (7).
C24H25NO: 343.1936 (correct HRMS).
[12]
[13]
M. Lautens, P. H. M. Delanghe, J. B. Goh, C. H. Zhang, J.
Ethyl cis-5-(Dibenzylamino)-2-cyclopentenecarboxylate (10): Treat-
ment of 3a (526 mg, 1 mmol) and ethyl trans-3-iodoacrylate
(452 mg, 2 mmol) according to the GP gave 10 (180 mg, 54%) as a
colorless oil after column chromatography (diethyl ether/pentane,
1:10, Rf ϭ 0.41). IR (film): ν˜ ϭ 3062 cmϪ1, 2926, 1734, 1457, 1363,
1206, 1163, 1029, 742, 698. 1H NMR (250 MHz, CDCl3): δ ϭ 1.24
Org. Chem. 1995, 60, 4213Ϫ4227.
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E. Piers, M. Jean, P. S. Marrs, Tetrahedron Lett. 1987, 28,
[14b]
5075Ϫ5078.
E. Piers, J. Banville, C. K. Lau, I. Nagakura,
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V. Farina, S. Kapadia, B. Krishnan, C. Wang, L. S. Liebeskind,
[15]
[16]
[17]
[18]
3
4
4
3
(t, J ϭ 7.1 Hz, 3 H, CH3), 2.42 (ddddd, J ϭ 2.0, J ϭ 2.2, J ϭ
2.2, 3J ϭ 4.5, 2J ϭ 17.8 Hz, 1 H, 4-H), 2.67 (ddddd, 4J ϭ 2.4, 4J ϭ
2.4, 3J ϭ 2.5, 3J ϭ 8.7, 2J ϭ 17.8 Hz, 1 H, 4-H), 3.55 (AB, d, 2J ϭ
14.0 Hz, 2 H, NCH2), 3.60 (AB, d, 2J ϭ 14.0 Hz, 2 H, NCH2), 3.70
J. Org. Chem. 1994, 59, 5905Ϫ5911.
[18a]
Reviews see:
73Ϫ135.
1151Ϫ1196.
H.-U. Reißig, Topics Curr. Chem. 1988, 144,
H.-U. Reißig, R. Zimmer, Chem. Rev. 2003, 103,
4
3
4
4
4
[18b]
(ddddd, J ϭ 2.1, J ϭ 2.1, J ϭ 2.2, J ϭ 2.4, J ϭ 4.1 Hz, 1 H,
3
3
3
1-H), 3.93 (ddd, J ϭ 4.1, J ϭ 4.5, J ϭ 8.7 Hz, 1 H, 5-H), 4.11
3
4
3
3
(q, J ϭ 7.1 Hz, 2 H, OCH2), 5.69 (dddd, J ϭ 2.1, J ϭ 2.2, J ϭ
Received July 22, 2003
Eur. J. Org. Chem. 2004, 631Ϫ635
www.eurjoc.org
 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
635