Straightforward access to α-methylamines through cross-metathesis

Article abstract of DOI:10.1055/s-0029-1218672

A two-step procedure involving cross-metathesis and reductive amination enables easy access to -methylamines and α,α′-dimethyldiamines from a wide variety of terminal olefins. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0029-1218672

1334
PAPER
Straightforward Access to a-Methylamines through Cross-Metathesis
M
ethylamines
l
throug
o
h
Cross-Met
r
a
Laboratoire de Chimie Moléculaire Organique, LCP UMR 6264, Boite 562, Université Paul Cézanne, Aix-Marseille III,
Faculté des Sciences St Jérôme, Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex 20, France
E-mail: stephane.gastaldi@univ-cezanne.fr
Laboratoire de Stéréochimie Dynamique et Chiralité, ISM2, UMR 6263, Université Paul Cézanne Aix-Marseille III,
Faculté des Sciences St Jérôme, Avenue Escadrille Normandie-Niemen, 13397 Marseille Cedex 20, France
b
Received 15 December 2009
metathesis reactions of electron-deficient substrates.12 Re-
ductive amination of 2 should afford a-methylamines 3.
Therefore, this strategy should provide a rapid access to a-
methylamines from the wide pool of commercially avail-
able or easily synthesized functionalized olefins.
Abstract: A two-step procedure involving cross-metathesis and re-
ductive amination enables easy access to a-methylamines and a,a¢-
dimethyldiamines from a wide variety of terminal olefins.
Key words: amines, alkenes, metathesis, ruthenium, hydrogena-
tion
O
NH2
MVK
NH3, MeOH
Pd/C (10%)
DCE, reflux
R
Amines are compounds of prime importance with a broad
spectrum of applications ranging from corrosion inhibi-
tors to synthetic intermediates in pharmaceutical or agro-
chemical industries.1
R
R
H2
1
2
3
N
N
Mes
Cl
Cl
Mes
Ru
O
Hoveyda–Grubbs II
catalyst
Our group is currently investigating kinetic resolution
(KR) of amines with the objective to devise a versatile dy-
namic kinetic resolution (DKR) method for amines in
which the stereocenter is directly adjacent to the amine
moiety.2 Selective chemoenzymatic DKR could be
achieved by the association of radical racemization3 with
enzymatic resolution by either lipases or proteases to pre-
pare either R-4 or S-acylated5 amines.
Primary a-methylamines are very good substrates in KR,6 roethane at reflux,13 afforded the desired a,b-unsaturated
because the steric discrimination between the two alkyl
groups at the stereogenic center is maximized by the pres-
i-Pr
Scheme 1 Cross-metathesis–reductive-amination sequence used
for the synthesis of a-methylamines
The reaction of alkene 1 (1 equiv) with methyl vinyl ke-
tone (3 equiv) in the presence of a catalytic amount (3
mol%) of the Hoveyda–Grubbs II catalyst, in 1,2-dichlo-
ketone 2 together with the methyl vinyl ketone dimer.
Yields ranged from 60 to 92%. As expected, CM with
ence of the smallest alkyl in the series, namely the methyl methyl vinyl ketone proceeded with total selectivity in
group.7
favor of the E-isomer; at this temperature no trace of the
Z-isomer was detected.14
To make a wide diversity of functionalized a-methyl-
amines available for DKR studies, a straightforward syn-
To investigate the scope of this reaction, the alkene func-
thesis needed to be developed. There are numerous tionalization was varied (Table 1). Terminal unfunction-
methodologies to synthesize primary amines, and it is im- alized olefins 1a and 1b (entries 1 and 2) and the
possible to list them all here.8 The reductive amination of conjugated alkene 1f (entry 6) gave very good yields. It
ketones,9 the addition of organometallic species to imine was also possible to perform the reaction on 1c or 1i with-
equivalents,10 or the reduction of nitro11 groups can be cit- out protection of the alcohol group (entries 3 and 9). Other
ed as examples among many.
functional groups such as esters 1d and 1g (entries 4 and
7), sulfone 1e (entry 5), and acetal 1h (entry 8) gave the
corresponding ketones in slightly lower yields (63–90%).
a,w-Terminal dienes 1i and 1j could similarly be used as
substrates (entries 9 and 10). It must be emphasized that a
cyclopentene resulting from ring-closing metathesis from
1i was not detected, although it is expected be an interme-
diate in the formation of 2i.15,16 The reactions of dienes 1i
and 1j led to double CM products 2i and 2j in quite good
yields. Ring-opening cross-metathesis (RO-CM)16 of cy-
clooctene (1k) led to the expected diketone 2k in very
good yield (entry 11). During the RO-CM step of cy-
clooctene (1k), six carbon atoms were incorporated into
the chain, whereas with linear diene 1j only four carbon
Over the past ten years, olefin metathesis has emerged as
a powerful synthetic tool.12 We wanted to use the advan-
tage of the compatibility of this reaction with a variety of
functional groups to design a short route to primary a-
methylamines. Our approach is depicted in Scheme 1. A
cross-metathesis (CM) reaction between a terminal alkene
1 and methyl vinyl ketone should lead to the a,b-unsatur-
ated ketone 2. The second-generation Hoveyda–Grubbs
catalyst was selected because of its ability to catalyze
SYNTHESIS 2010, No. 8, pp 1334–1338
Advanced online publication: 05.02.2010
DOI: 10.1055/s-0029-1218672; Art ID: P16609SS
x
x
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x
x
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0
1
0
© Georg Thieme Verlag Stuttgart · New York

PAPER
Methylamines through Cross-Metathesis
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Table 1 Synthesis of a-Methylamines from Various Functionalized Alkenes
Entry Alkene 1
Ketone 2
Yield Amine 3
(%)
Yield
(%)
1
2
1a dodec-1-ene
2a
92
81
3a
3b
90b
93b
NH2
Ph
O
Ph
1b allylbenzene
1c dec-9-en-1-ol
2b
NH2
O
OH
OH
3
4
5
2c
86
70
67
3c
3d
3e
69c
NH2
O
CO2Et
CO2Et
CO2Et
CO2Et
CO2Et
1d
1e
2d
57c,d
54c
O
NH2
NH2
CO2Et
Ts
O
2e
Ts
Ts
NH2
O
6
7
1f 2-vinylnaphthalene
2f
81
3f
82c
71c
77c
CO2Me
CO2Me
1g
2g
63a
90a
3g
3h
CO2Me
NH2
NH2
O
O
O
O
O
8
9
1h
2h
O
O
O
1i
2i
60
63
3i
3j
84b
89b
OH
OH
NH2
H2N
O
OH
O
NH2
NH2
O
O
O
10 1j
2j
O
O
O
O
O
2
2
2
NH2
NH2
O
11 1k cyclooctene
2k
92
3k
69b
O
a Partially contaminated with MVK dimer.
b Product can be used without further purification.
c Purified on a short pad of silica.
d An NH3/EtOH solution was used.
atoms were introduced (entry 10, 2j). This provides a fast ple filtration over Celite or after flash chromatography on
entry to fatty alkylamines.
a short column of silica. According to the same procedure,
diketones 2i–k led very cleanly to a,a¢-dimethyldiamines
3i–k (entries 9–11).
All the ketones were then submitted to reductive amina-
tion in a three molar solution of ammonia in methanol in
the presence of palladium (10%) on activated carbon un- In conclusion, this two-step procedure offers an easy and
der a hydrogen atmosphere (8 bar). To avoid the forma- efficient access to a-methylamines. Its ease of use makes
tion of side products resulting from competitive Michael it competitive with the approaches already reported in the
addition, the reduction of the double bond had to be fast. literature. Furthermore, this methodology applies to
Under the above conditions, amines and diamines were dienes and cycloolefins and allows the synthesis of sym-
obtained in good yields. No aminolysis of ester groups or metrical a,a¢-dimethyldiamines, which are very interest-
cyclization into lactams was detected (entries 4 and 7). ing candidates for further DKR studies.17
The presence of the methyl vinyl ketone dimer did not in-
terfere with the reductive amination step (entries 7 and 8),
and its reductive amination product was not detected after
purification. The products were recovered by either sim-
All reactions were carried out in dry glassware and by using mag-
netic stirring and a positive pressure of argon. Commercially avail-
able solvents were used as purchased, without further purification.
Synthesis 2010, No. 8, 1334–1338 © Thieme Stuttgart · New York

1336
F. Poulhès et al.
PAPER
Dry state adsorption and purification were performed on Macherey
Nagel silica gel 60 Å (70–230 mesh). Analytical TLC was per-
formed on precoated silica gel plates. Visualization was accom-
plished by UV (254 nm) and with phosphomolybdic acid in ethanol.
1H NMR and 13C NMR spectra were recorded at 300 MHz and 75
MHz, respectively, on a Bruker spectrometer. Signals due to resid-
ual undeuterated solvent (1H NMR, CDCl3, d = 7.27) or to the sol-
vent (13C NMR, CDCl3, d = 77.0) served as the internal standards.
DEPT 135 was used for 13C spectral assignment. HRMS (TOF,
ES+) was carried out on a QStar Elite (Applied Biosystems SCIEX)
mass spectrometer. MVK was distilled prior to use. Alkenes 1a–d,
1f, 1i, and 1k and the ruthenium catalyst were commercially avail-
able. Alkenes 1e18 and 1h19 were prepared according to literature
procedure. Alkene 1g was prepared by esterification of the commer-
cially available corresponding carboxylic acid. Alkene 1j was ob-
tained by a standard allylation procedure (NaH/THF).
HRMS (TOF, ES+): m/z [M + H]+ calcd for C12H19O5: 243.1227;
found: 243.1224.
(E)-5-Tosylpent-3-en-2-one (2e)
1H NMR (300 MHz, CDCl3): d = 7.76 (d, J = 8.3 Hz, 2 H), 7.38 (d,
J = 8.3 Hz, 2 H), 6.63 (dt, J = 15.9, 7.7 Hz, 1 H), 6.05 (dt, J = 15.9,
1.1 Hz, 1 H), 3.94 (dd, J = 7.7, 1.1 Hz, 2 H), 2.47 (s, 3 H), 2.27 (s,
3 H).
13C NMR (75 MHz, CDCl3): d = 197.4 (C=O), 145.8 (C=), 138.1
(HC=), 135.6 (C=), 132.2 (HC=), 130.4 (HC=), 128.7 (HC=), 59.9
(CH2), 27.7 (CH3), 22.1 (CH3).
HRMS (TOF, ES+): m/z [M + NH4]+ calcd for C12H18NO3S:
256.1002; found: 256.1003.
(E)-4-(2-Naphthyl)but-3-en-2-one (2f)
1H NMR (300 MHz, CDCl3): d = 7.99 (br s, 1 H), 7.92–7.83 (m, 3
H), 7.71 (d, J = 16.3 Hz, 1 H), 7.70 (dd, J = 8.8, 1.8 Hz, 1 H), 7.58–
7.51 (m, 2 H), 6.86 (d, J = 16.3 Hz, 1 H), 2.45 (s, 3 H).
Ketones 2 by Cross-Metathesis; General Procedure
The catalyst (3 mol%) was added to a 0.1 M soln of alkene 1 (1
mmol) and MVK (3 mmol) in DCE. The mixture was stirred at re-
flux for 0.5–1 h (TLC monitoring). Then the solvent was evaporated
under reduced pressure and the residue was purified by flash chro-
matography (silica gel, EtOAc–pentane); this afforded pure ketone
2.
13C NMR (75 MHz, CDCl3): d = 198.7 (C=O), 143.9 (HC=), 134.7
(C=), 133.7 (C=), 132.3 (C=), 130.7 (HC=), 129.2 (HC=), 129.0
(HC=), 128.2 (HC=), 127.8 (HC=), 127.7 (HC=), 127.2 (HC=),
123.9 (HC=), 28.0 (CH3).
HRMS (TOF, ES+): m/z [M + H]+ calcd for C14H13O: 197.0961;
found: 197.0957.
(E)-Tetradec-3-en-2-one (2a)
1H NMR (300 MHz, CDCl3): d = 6.76 (dt, J = 15.9, 7.0 Hz, 1 H),
6.02 (dt, J = 15.9, 1.5 Hz, 1 H), 2.22–2.12 (m, 2 H), 2.19 (superim-
posed s, 3 H), 1.49–1.35 (m, 2 H), 1.34–1.14 (m, 14 H), 0.83 (t,
J = 6.4 Hz, 3 H).
(E)-Methyl 6-Oxohept-4-enoate (2g)
1H NMR (300 MHz, CDCl3) (mixture with (E)-hex-3-ene-2,5-di-
one): d = 6.80 (dt, J = 16.0, 6.4 Hz, 1 H), 6.11 (dt, J = 16.0, 1.5 Hz,
1 H), 3.70 (s, 3 H), 2.60–2.45 (m, 4 H), 2.25 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 198.9 (C=O), 148.9 (HC=), 131.6
(HC=), 32.8 (CH2), 32.2 (CH2), 29.9 (CH2), 29.8 (CH2), 29.7 (CH2),
29.6 (CH2), 29.5 (CH2), 28.4 (CH2), 27.1 (CH3), 23.0 (CH2), 15.4
(CH3).
HRMS (TOF, ES+): m/z [M + H]+ calcd for C14H27O: 211.2056;
found: 211.2050.
13C NMR (75 MHz, CDCl3): d = 198.7 (C=O), 173.0 (C=O), 146.0
(HC=), 132.1 (HC=), 52.1 (CH3), 32.5 (CH2), 27.7 (CH2), 27.3
(CH3).
HRMS (TOF, ES+): m/z [M + H]+ calcd for C8H13O3: 157.0859;
found: 157.0855.
(E)-6-(2-Methyl-1,3-dioxolan-2-yl)hex-3-en-2-one (2h)
1H NMR (300 MHz, CDCl3) (mixture with (E)-hex-3-ene-2,5-di-
one): d = 6.80 (dt, J = 15.9, 6.8 Hz, 1 H), 6.11 (br d, J = 15.9 Hz, 1
H), 4.00–3.85 (m, 4 H), 2.33 (pseudo q, J = 7.7 Hz, 2 H), 2.21 (s, 3
H), 1.8 (m, 2 H), 1.31 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 199.7 (C=O), 149.3 (HC=), 132.2
(HC=), 110.4 (C), 65.8 (2 × CH2), 38.4 (CH2), 28.1 (CH2), 27.8
(CH3), 25.1 (CH3).
(E)-5-Phenylpent-3-en-2-one (2b)
1H NMR (300 MHz, CDCl3): d = 7.40–7.17 (m, 5 H), 6.94 (dt,
J = 15.9, 6.8 Hz, 1 H), 6.10 (dt, J = 15.9, 1.5 Hz, 1 H), 3.56 (br d,
J = 6.8 Hz, 2 H), 2.26 (s, 3 H).
13C NMR (75 MHz, CDCl3): d = 198.9 (C=O), 146.7 (HC=), 138.0
(C=), 132.4 (HC=), 129.2 (HC=), 129.1 (HC=), 127.2 (HC=), 39.2
(CH2), 27.3 (CH3).
HRMS (TOF, ES+): m/z [M + H]+ calcd for C11H13O: 161.0961;
found: 161.0960.
HRMS (TOF, ES+): m/z [M + NH4]+ calcd for C10H20NO3:
202.1438; found: 202.1437.
(E)-12-Hydroxydodec-3-en-2-one (2c)
(3E,8E)-6-Hydroxy-6-methylundeca-3,8-diene-2,10-dione (2i)
1H NMR (300 MHz, CDCl3): d = 6.83 (dt, J = 16.0, 7.6 Hz, 2 H),
6.16 (dt, J = 16.0, 1.1 Hz, 2 H), 2.43 (m, 4 H), 2.43 (s, 6 H), 1.28 (s,
3 H).
13C NMR (75 MHz, CDCl3): d = 198.7 (C=O), 143.0 (HC=), 134.7
(HC=), 45.5 (CH2), 27.7 (CH3), 27.6 (2 × CH3).
HRMS (TOF, ES+): m/z [M + H]+ calcd for C12H19O3: 211.1329;
1H NMR (300 MHz, CDCl3): d = 6.81 (dt, J = 16.0, 6.8 Hz, 1 H),
6.08 (dt, J = 16.0, 1.5 Hz, 1 H), 3.66 (t, J = 6.6 Hz, 2 H), 2.28–2.18
(m, 2 H), 2.25 (s, 3 H), 1.60–1.45 (m, 5 H), 1.33 (m, 8 H).
13C NMR (75 MHz, CDCl3): d = 199.2 (C=O), 149.0 (HC=), 131.7
(HC=), 63.3 (CH2), 33.1 (CH2), 32.8 (CH2), 29.7 (CH2), 29.6 (CH2),
29.5 (CH2), 28.4 (CH2), 27.2 (CH3), 26.1 (CH2).
HRMS (TOF, ES+): m/z [M + H]+ calcd for C12H23O2: 199.1693;
found: 199.1696.
found: 211.1330.
(3E,14E)-6,9,12-Trioxaheptadeca-3,14-diene-2,16-dione (2j)
1H NMR (300 MHz, CDCl3): d = 6.80 (dt, J = 16.2, 4.5 Hz, 2 H),
6.32 (dt, J = 16.2, 1.7 Hz, 2 H), 4.24 (dd, J = 4.5, 1.7 Hz, 4 H), 3.69
(m, 8 H), 2.29 (s, 6 H).
13C NMR (75 MHz, CDCl3): d = 198.6 (C=O), 143.4 (HC=), 130.8
(HC=), 71.1 (CH2), 70.8 (CH2), 70.4 (CH2), 27.6 (CH3).
Diethyl 2-[(E)-4-Oxopent-2-enyl]malonate (2d)
1H NMR (300 MHz, CDCl3): d = 6.75 (dt, J = 16.0, 7.0 Hz, 1 H),
6.13 (dt, J = 16.0, 1.3 Hz, 1 H), 4.23 (ABX3, 4 H), 3.50 (t, J = 7.3
Hz, 1 H), 2.81 (td, J = 7.3, 1.5 Hz, 2 H), 2.24 (s, 3 H), 1.27 (t, J = 7.2
Hz, 6 H).
13C NMR (75 MHz, CDCl3): d = 198.4 (C=O), 168.7 (C=O), 143.2
(HC=), 133.5 (HC=), 62.1 (CH2), 51.0 (CH), 31.7 (CH2), 27.4
(CH3), 14.4 (CH3).
HRMS (TOF, ES+): m/z [M + H]+ calcd for C14H23O5: 271.1540;
found: 271.1533.
Synthesis 2010, No. 8, 1334–1338 © Thieme Stuttgart · New York

PAPER
Methylamines through Cross-Metathesis
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(3E,11E)-Tetradeca-3,11-diene-2,13-dione (2k)
H), 2.43 (s, 3 H), 1.83 (br s, 2 H), 1.80–1.67 (m, 2 H), 1.42–1.32 (m,
2 H), 1.03 (d, J = 6.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 145.0 (C=), 136.5 (C=), 130.3
(HC=), 128.4 (HC=), 56.6 (CH2), 46.9 (CH), 38.4 (CH2), 24.0
(CH3), 22.0 (CH3), 20.1 (CH2).
HRMS (TOF, ES+): m/z [M + H]+ calcd for C12H20NO2S: 242.1209;
found: 242.1208.
1H NMR (300 MHz, CDCl3): d = 6.79 (dt, J = 16.0, 6.8 Hz, 2 H),
6.10 (dt, J = 16.0, 1.5 Hz, 2 H), 2.30–2.15 (m, 4 H), 2.28 (superim-
posed s, 6 H), 1.57–1.40 (m, 4 H), 1.40–1.29 (m, 4 H).
13C NMR (75 MHz, CDCl3): d = 199.0 (C=O), 148.7 (HC=), 131.7
(HC=), 32.7 (CH2), 29.3 (CH2), 28.3 (CH2), 27.2 (CH3).
HRMS (TOF, ES+): m/z [M + H]+ calcd for C14H23O2: 223.1693;
found: 223.1691.
4-(2-Naphthyl)butan-2-amine (3f)
Amines 3 by Reductive Amination of Ketones 2; General Proce-
dure
1H NMR (300 MHz, CDCl3): d = 7.75–7.97 (m, 3 H), 7.65 (br s, 1
H), 7.52–7.40 (m, 2 H), 7.36 (dd, J = 8.5, 1.7 Hz, 1 H), 2.99 (sext,
J = 6.3 Hz, 1 H), 2.85 (m, 2 H), 1.88 (br s, 2 H), 1.79 (m, 2 H), 1.17
(d, J = 6.3 Hz, 3 H).
Pd/C (10%, 80 mg) was added to a 0.05 M soln of ketone 2 (1
mmol) in a 3 M soln of NH3 in MeOH. The mixture was stirred
overnight at r.t. under H2 pressure (8 bar). After filtration over
Celite, the residue was purified by flash chromatography on a short
column of silica gel (MeOH–Et3N–CH2Cl2, 1.6:1.6:96.8); this af-
forded pure amine 3.
13C NMR (75 MHz, CDCl3): d = 140.2 (C=), 134.1 (C=), 132.4
(C=), 128.3 (HC=), 128.0 (HC=), 127.8 (HC=), 127.7 (HC=), 126.7
(HC=), 126.3 (HC=), 125.5 (HC=), 47.0 (CH), 41.9 (CH2), 33.3
(CH2), 24.3 (CH3).
HRMS (TOF, ES+): m/z [M + H]+ calcd for C14H18N: 200.1434;
found: 200.1441.
Tetradecan-2-amine (3a)
1H NMR (300 MHz, CDCl3): d = 2.87 (sext, J = 6.0 Hz, 1 H), 1.85
(br s, 2 H), 1.45–1.15 (m, 22 H), 1.05 (d, J = 6.0 Hz, 3 H), 0.87 (t,
J = 6.4 Hz, 3 H).
Methyl 6-Aminoheptanoate (3g)
1H NMR (300 MHz, CDCl3): d = 6.60 (br s, 2 H), 3.65 (s, 3 H), 3.20
(sext, J = 6.4 Hz, 1 H), 2.30 (t, J = 7.4 Hz, 2 H), 1.80–1.50 (m, 4 H),
1.49–1.33 (m, 2 H), 1.25 (d, J = 6.4 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 47.3 (CH), 40.5 (CH2), 32.3 (CH2),
30.1 (CH2), 30.0 (br, 5 × CH2), 29.7 (CH2), 26.8 (CH2), 24.2 (CH3),
23.1 (CH2), 14.5 (CH3).
HRMS (TOF, ES+): m/z [M + H]+ calcd for C14H32N: 214.2529;
found: 214.2525.
13C NMR (75 MHz, CDCl3): d = 174.2 (C=O), 51.9 (CH3), 48.2
(CH), 35.8 (CH2), 34.0 (CH2), 25.5 (CH2), 24.8 (CH2), 19.9 (CH3).
HRMS (TOF, ES+): m/z [M + H]+ calcd for C8H18NO2: 160.1332;
found: 160.1330.
5-Phenylpentan-2-amine (3b)
1H NMR (300 MHz, CDCl3): d = 7.35–7.10 (m, 5 H), 2.92 (sext,
J = 6.4 Hz, 1 H), 2.63 (t, J = 7.6 Hz, 2 H), 2.08 (br s, 2 H), 1.65 (m,
2 H), 1.39 (m, 2 H), 1.08 (d, J = 6.2 Hz, 3 H).
6-(2-Methyl-1,3-dioxolan-2-yl)hexan-2-amine (3h)
1H NMR (300 MHz, CDCl3): d = 3.98–3.80 (m, 4 H), 2.85 (sext,
J = 6.1 Hz, 1 H), 1.89 (br s, 2 H), 1.64–1.56 (m, 2 H), 1.42–1.20 (m,
6 H), 1.26 (superimposed s, 3 H), 1.02 (d, J = 6.1 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 142.8 (C=), 128.8 (HC=), 128.7
(HC=), 126.1 (HC=), 47.3 (CH), 39.7 (CH2), 36.4 (CH2), 28.7
(CH2), 23.9 (CH3).
HRMS (TOF, ES+): m/z [M + H]+ calcd for C11H18N: 164.1434;
found: 164.1436.
13C NMR (75 MHz, CDCl3): d = 110.4 (C), 64.9 (2 × CH2), 47.2
(CH), 40.3 (CH2), 39.5 (CH2), 26.9 (CH2), 24.5 (CH2), 24.1
(2 × CH3).
HRMS (TOF, ES+): m/z [M + H]+ calcd for C10H22NO2: 188.1645;
found: 188.1642.
11-Aminododecan-1-ol (3c)
1H NMR (300 MHz, CDCl3): d = 4.5 (br s, 3 H), 3.62 (t, J = 6.6 Hz,
2 H), 3.09 (sext, J = 6.4 Hz, 1 H), 1.62–1.45 (m, 4 H), 1.42–1.24 (m,
14 H), 1.22 (d, J = 6.4 Hz, 3 H).
2,10-Diamino-6-methylundecan-6-ol (3i)
1H NMR (300 MHz, CDCl3) (mixture of diastereomers): d = 2.91
(sext, J = 6.2 Hz, 2 H), 2.00–1.80 (br s, 5 H), 1.50–1.25 (m, 12 H),
1.17 (s, 3 H), 1.08 (d, J = 6.2 Hz, 6 H).
13C NMR (75 MHz, CDCl3): d = 63.2 (CH2), 45.7 (CH), 33.2 (CH2),
30.0 (CH2), 29.9 (2 × CH2), 29.9 (CH2), 29.8 (CH2), 29.7 (CH2),
26.6 (CH2), 26.1 (CH2), 23.1 (CH3).
HRMS (TOF, ES+): m/z [M + H]+ calcd for C12H28NO: 202.2165;
found: 202.2164.
13C NMR (75 MHz, CD3OD): d = 72.5 (C), 48.0 (CH), 42.0 (CH2),
41.9 (CH2), 41.8 (CH2), 41.8 (CH2), 37.3 (CH2), 26.2 (CH3), 26.1
(2 × CH3), 26.0 (CH3), 20.6 (CH2), 19.7 (CH3).
Because of the presence of phthalate residues in the mass spectrom-
eter interfering with the mass determination of 3i, HRMS analysis
had to be performed after derivatization in bis(trifluoroacetamide)
with N-methylbis(trifluoroacetamide) (3 equiv).
HRMS (TOF, ES+): m/z [M + NH4]+ calcd for C16H26N3O3F6:
426.2186; found: 426.2188.
Diethyl 2-(4-Aminopentyl)malonate (3d)
1H NMR (300 MHz, CDCl3): d = 5.40 (br s, 2 H), 4.15 (q, J = 7.2
Hz, 4 H), 3.30 (t, J = 7.5 Hz, 1 H), 3.11 (sext, J = 6.3 Hz, 1 H), 1.86
(q, J = 7.5 Hz, 2 H), 1.68–1.32 (m, 4 H), 1.23 (t, J = 7.2 Hz, 6 H),
1.21 (d, J = 6.3 Hz, 3 H).
13C NMR (75 MHz, CDCl3): d = 169.7 (C=O), 61.7 (CH2), 52.2
(CH), 47.8 (CH), 37.0 (CH2), 28.7 (CH2), 24.1 (CH2), 21.1 (CH3),
14.4 (CH3).
HRMS (TOF, ES+): m/z [M + H]+ calcd for C12H24NO4: 246.1700;
found: 246.1698.
5-{2-[2-(4-Aminopentyloxy)ethoxy]ethoxy}pentan-2-amine (3j)
1H NMR (300 MHz, CDCl3): d = 4.00 (br s, 4 H), 3.60 (m, 8 H), 3.49
(t, J = 6.2 Hz, 4 H), 3.07 (m, 2 H), 1.70–1.45 (m, 8 H), 1.17 (d,
J = 5.5 Hz, 6 H).
13C NMR (75 MHz, CDCl3): d = 71.6 (CH2), 70.7 (CH2), 70.4
(CH2), 47.5 (CH), 35.4 (CH2), 26.6 (CH2), 22.5 (CH3).
5-Tosylpentan-2-amine (3e)
1H NMR (300 MHz, CDCl3): d = 7.76 (d, J = 8.3 Hz, 2 H), 7.34 (d,
J = 8.3 Hz, 2 H), 3.60 (t, J = 7.9 Hz, 2 H), 2.86 (sext, J = 6.4 Hz, 1
HRMS (TOF, ES+): m/z [M + H]+ calcd for C14H33N2O3: 277.2486;
found: 277.2491.
Synthesis 2010, No. 8, 1334–1338 © Thieme Stuttgart · New York

1338
F. Poulhès et al.
PAPER
2nd ed.; Wiley-VCH: Weinheim, 2006, Chap. 6 and
Tetradecane-2,13-diamine (3k)
1H NMR (300 MHz, CDCl3): d = 2.84 (sext, J = 6.2 Hz, 2 H), 2.00–
1.85 (br s, 4 H), 1.35–1.20 (m, 20 H), 1.03 (d, J = 6.2 Hz, 6 H).
references cited therein.
(8) For a review on the synthesis of a-branched chiral amines,
see: Bräse, S.; Baumann, T.; Dahmen, S.; Vogt, H. Chem.
Commun. 2007, 1881.
(9) For a review, see: (a) Gomez, S.; Peters, J. A.; Maschmeyer,
T. Adv. Synth. Catal. 2002, 344, 1037. (b) Tararov, V. I.;
Börner, A. Synlett 2005, 203. (c) Tripathi, R. P.; Verma, S.
S.; Pandey, J.; Tiwari, V. K. Curr. Org. Chem. 2008, 12,
1093.
(10) For a review, see: Ferraris, D. Tetrahedron 2007, 63, 9581.
(11) For a review, see: Barrett, A. G. M.; Graboski, G. G. Chem.
Rev. 1986, 86, 751.
(12) For a review dealing with olefin cross-metathesis, see:
Connon, S. J.; Blechert, S. Angew. Chem. Int. Ed. 2003, 42,
1900.
(13) Michaut, A.; Boddaert, T.; Coquerel, Y.; Rodriguez, J.
Synthesis 2007, 2867.
(14) Gessler, S.; Randl, S.; Blechert, S. Tetrahedron Lett. 2000,
41, 9973.
(15) Monfette, S.; Fogg, D. E. Chem. Rev. 2009, 109, 3783.
(16) For selected examples of ring-opening cross-metathesis,
see: (a) Roe, S. J.; Legeay, J.-C.; Robbins, D.; Aggarwal, P.;
Stockman, R. A. Chem. Commun. 2009, 4399. (b) Randl,
S.; Connon, S. J.; Blechert, S. Chem. Commun. 2001, 1796.
(c) Morgan, J. P.; Morrill, C.; Grubbs, R. H. Org. Lett. 2002,
4, 67.
13C NMR (75 MHz, CDCl3): d = 48.1 (CH), 39.5 (CH2), 30.2 (br,
CH2), 30.0 (br, CH2), 26.8 (CH2), 23.3 (CH3).
HRMS (TOF, ES+): m/z [M + H]+ calcd for C14H33N2: 229.2638;
found: 229.2634.
Acknowledgment
This work was supported by the Agence Nationale de la Recherche
(ANR 06-Blan-0137).
References
(1) Lawrence, S. A. Amines: Synthesis, Properties and
Applications; Cambridge University Press: Cambridge,
2004.
(2) (a) Nechab, M.; Azzi, N.; Vanthuyne, N.; Bertrand, M. P.;
Gastaldi, S.; Gil, G. J. Org. Chem. 2007, 72, 6918.
(b) El Blidi, L.; Nechab, M.; Vanthuyne, N.; Gastaldi, S.;
Bertrand, M. P.; Gil, G. Org. Biomol. Chem. 2008, 6, 3917.
(3) Routaboul, L.; Vanthuyne, N.; Gastaldi, S.; Gil, G.;
Bertrand, M. P. J. Org. Chem. 2008, 73, 364.
(4) Gastaldi, S.; Escoubet, S.; Vanthuyne, N.; Gil, G.; Bertrand,
M. P. Org. Lett. 2007, 9, 837.
(5) El Blidi, L.; Nechab, M.; Vanthuyne, N.; Gastaldi, S.; Gil,
G.; Bertrand, M. P. J. Org. Chem. 2009, 74, 2901.
(6) van Rantwijk, F.; Sheldon, R. A. Tetrahedron 2004, 60, 501;
and references cited therein.
(17) Veld, M. A. J.; Hult, K.; Palmans, A. R. A.; Meijer, E. W.
Eur. J. Org. Chem. 2007, 5416.
(18) Crandall, J. K.; Pradat, C. J. Org. Chem. 1985, 50, 1327.
(19) Lanners, S.; Norouzi-Arasi, H.; Khiri, N.; Hanquet, G. Eur.
J. Org. Chem. 2007, 4065.
(7) Bornscheuer, U. T.; Kazlauskas, R. J. Hydrolases in Organic
Synthesis: Regio- and Stereoselective Biotransformations,
Synthesis 2010, No. 8, 1334–1338 © Thieme Stuttgart · New York