Vicinal diamination of terminal olefins

Article abstract of DOI:10.1002/hlca.200590119

The present publication describes an efficient and mild three-step conversion of a terminal olefin 1 into the corresponding 1,2-diamine 5. The sequence includes: azidoiodination, substitution with NaN₃, and catalytic hydrogenolysis. The termina

Full text of DOI:10.1002/hlca.200590119

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Helvetica Chimica Acta ± Vol. 88 (2005)
Vicinal Diamination of Terminal Olefins
by Hans Rudolf Pfaendler* and Alexander Klingl
Department of Chemistry and Biochemistry, University of Munich, Butenandtstrasse 5 ± 13, Haus F,
D-81377 Munich
(phone: ‡ 4989218077770; fax: ‡ 4989218077771; e-mail: hrp@cup.uni-muenchen.de)
Dedicated to Professor Rolf Huisgen on the occasion of his 85th birthday
The present publication describes an efficient and mild three-step conversion of a terminal olefin 1 into the
corresponding 1,2-diamine 5. The sequence includes: azidoiodination, substitution with NaN3, and catalytic
hydrogenolysis. The terminal 1,2-diamine 5 was converted into its cis-dichloroplatinum(II) complex 6.
Introduction. ± Reagents that oxidize olefins to vicinal diols belong to the standard
tools in synthetic organic chemistry. On the other hand, the transformation of alkenes
leading to the corresponding vicinal diamines is far more difficult to achieve and has
been the subject of several investigations. An early stereospecific multistep conversion
was realized via oxiranes or aziridines as intermediates [1]. Other methods were limited
to conjugated dienes as starting materials [2] or led to N,N-disubstituted or N,N,N-
trisubstituted 1,2-diamines as products [3]. A stereospecific 1,2-diamination of simple
aliphatic olefins used a prepared nitrosyl-Co complex, gaseous NO, and LiAlH4 [4].
During our investigations of new ether lipid-linked Pt complexes as potential
antineoplastic agents [5], we evaluated several synthetic preparations leading to
aliphatic 1,2-diamines.
Results and Discussion. ± We wish to report here a convenient and efficient three-
step process with conventional and commercially available reagents. It is exemplified
by the following preparation: 10-(benzyloxy)dec-1-ene (1) reacted at 08 with the IN3 ´
NaN3 complex [6] to give 2-azido-10-(benzyloxy)-1-iododecane (2; Scheme). ± The
IN3 ´ NaN3 complex was prepared from iodine monochloride and NaN3 according to the
method of Hassner and co-workers [7]. A full conversion, 1 ! 2, was achieved when 1.3
equiv. of the IN3 ´ NaN3 reagent was prepared in situ (without removal of NaCl and
excess NaN3) at À 158, followed by subsequent addition of olefin 1. After workup,
chromatographic purification of the crude product led to pure 2 in 72% yield. However,
for further synthesis it was more convenient to proceed with the crude material 2
obtained in 99% yield.
Subsequently, the azido-iodo intermediate 2 was converted to 1,2-diazido-10-
(benzyloxy)decane (3) with NaN3. Initially, when the conversion 2 ! 3 was carried out
in DMF with Bu4NBr as phase-transfer catalyst, the reaction required 48h at 100 8 for
completion. Alvarez and Alvarez [8] suggested to prepare alkyl azides in DMSO, which
dissolves NaN3 much better than most other dipolar aprotic solvents. Indeed, in DMSO
ꢀ 2005 Verlag Helvetica Chimica Acta AG, Zürich

Helvetica Chimica Acta ± Vol. 88 (2005)
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Scheme
the above reaction proceeded smoothly at room temperature within 20 h. After
workup, chromatographic purification on silica gel gave pure 3 in 78% yield.
Aliphatic amines can poison hydrogenation catalysts [9]. This might be the reason
why the hydrogenolysis of 3 in EtOH Pd/C led to 10-(benzyloxy)decane-1,2-diamine
(4), without removing the Bn protection group. However, we found that complete
hydrogenolysis could be easily achieved upon addition of 2 equiv. of HCl. This
procedure quantitatively yielded pure 9,10-diaminodecan-1-ol dihydrochloride (5, m.p.
125 ± 1288).
Finally, the diamino-alcohol 5 reacted with K2PtCl4 at 658 to give the yellow
platinum complex 6 in 79% yield.
Different from earlier methods, our three-step sequence avoids intermediates,
delicate to handle, such as aziridines. An other advantage lies in the mild reduction
process of the vicinal diazide intermediate 3 with H2, facilitating workup of the
diamines 4 or 5. In our hands, the above sequence was the method of choice for the
conversion of terminal aliphatic olefins into vicinal diamines.
Experimental Part
General. Reactions were carried out in dry glassware and under dry N2. Reagents were purchased from
Fluka and Aldrich. Dry MeCN and DMSO (stored over molecular sieves) were purchased from Fluka (Product
Nos. 00695 and 41647) and not purified further. THF was freshly distilled over LiAlH4 before use. TLC was
performed on 0.2-mm Merck silica gel-60-F254 plates. TLC plates were investigated for UV absorption, after
staining in the I2 chamber and/or after spraying with a 10% soln. of molybdophosphoric acid (MPA) in EtOH,
followed by development with a heat gun. From concentrated solns. a sample was diluted with an appropriate
solvent before spotting. From DMSO solns. small samples were diluted with hexane/AcOEt 9 :1 and washed
with a few drops of H2O prior to spotting on TLC. IR Spectra were recorded on a Perkin-Elmer 1420-Ratio-
Recording and on a Nicolet 520 FT-IR-spectrometer. 1H- and 13C-NMR spectra were recorded on a Bruker
ARX-300 and a Varian VXR-400-S spectrometer. Reaction monitoring was performed on a Varian Mercury-200
spectrometer. Mass spectra were recorded on a Finigan MAT-90 and a Finigan MAT-90-Q spectrometer. The
method of ionization is indicated with the reported spectral data. Electron ionization (EI), chemical ionization

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Helvetica Chimica Acta ± Vol. 88 (2005)
(CI), and fast atom bombardment (FAB) were the applied methods. 2-Nitrobenzyl alcohol was used as sample
matrix and the reacting gas was isobutane. The molecular peak and characterized fragment peaks are given as
well as all signals, having a relative intensity of 10% or more. Elemental analysis was performed in a Heraeus
(Universal Standard) apparatus.
10-(Benzyloxy)dec-1-ene (1). In a 100-ml three-necked flask, fitted with a magnetic stirrer, thermometer,
rubber septum, and a bubbler, to a dispersion of NaH in mineral oil (60% NaH, 2.00 g, 50 mmol) in dry THF
(40 ml) were added BnBr (7.66 g, 44.8mmol) and dec-9-en-1-ol within 5 min at r.t. The reaction mixture was
allowed to stir at r.t. overnight until gas evolution came to an end. The colorless mixture was poured on ice water
and extracted twice with portions (400 ml) of AcOEt. The combined AcOEt layers were washed twice with
portions (400 ml) of sat. aq. NaCl, dried (MgSO4), filtered, and the solvent was removed in vacuo to leave a
yellow oil (12.00 g). Chromatographic purification on silica gel (450 g; 0.063 ± 0.200 mm) with toluene (10
Fractions, 400 ml each) gave 1 as a colorless oil (10.03 g, 91 %) from Fr. 6 and 7, after drying in high vacuum. Rf
(hexane/AcOEt 9 :1) 0.5. IR (CH2Cl2): 3030w, 2930vs, 2850s, 1725w, 1635w, 1490w, 1450m, 1360w, 1200w, 1095m,
1
1025w, 995w, 910m. H-NMR (CDCl3, 300 MHz): 1.15 ± 1.45 (m, CH2(4), CH2(5), CH2(6), CH2(7), CH2(8));
1.53 ± 1.68( m, HÀC(9)); 1.95 ± 2.10 (m, CH2(3)); 3.45 (t, 3J ˆ 6.6, CH2(10)); 4.48( s, PhCH2); 4.89 ± 4.95 (m, 3J ˆ
10.2, 2J ˆ 2.2, 1 HÀ(1)); 4.95 ± 5.03 (m, 3J ˆ 17.1, 2J ˆ 2.2, 1 HÀC(1)); 5.80 (ddt, J ˆ 17.1, 10.2, 6.6, HÀC(2));
7.18± 7.40 ( m, 5 arom. H). 13C-NMR (CDCl3, 75 MHz): 26.2 (C(8)); 28.9, 29.1, 29.4, 29.8 (C(2, 4, 5, 6, 7, 9)); 33.8
(C(3)); 70.5 (C(10)), 72.8(Ph CH2), 114.1 (C(1)); 127.4, 127.6, 128.3, 138.7, 139.1 (arom. C). FAB-MS: 246 (2,
‡
‡
M ), 245, (24, [M À H] ), 147 (12), 123 (23), 111 (20), 109 (30), 107 (62), 105 (28), 103 (51), 101 (64), 93 (15),
‡
91 (98, C7H7 ), 85 (28), 83 (70), 81 (50), 79 (20), 77 (11), 74 (24), 71 (44), 69 (86), 67 (35), 57 (78), 55 (100), 43
(56), 41 (42). Anal. calc. for C17H26O (246.39): C 82.87, H 10.64; found: C 82.29, H 10.92.
2-Azido-10-(benzyloxy)-1-iododecane (2). In a 25-ml Schlenk flask, fitted with a magnetic stirrer and a
rubber septum, to a suspension of NaN3 (211 mg, 3.25 mmol) in MeCN (1.0 ml) was added a soln. of ICl (211 mg,
1.30 mmol) in MeCN (1.0 ml) at À 158. After 10 min, neat 1 (246 mg, 270 ml, 1.00 mmol) was added at À 158 by
means of a precision syringe within 15 min, and the mixture allowed to warm to r.t. Stirring was continued at r.t.
After 2 h, TLC indicated a full conversion. Hexane (15 ml) and H2O (15 ml) were added, and the violet color
(I2) of the org. layer was removed by addition of a few drops of a 10% aq. soln. of sodium thiosulfate. The org.
layer was washed again with H2O (15 ml), and the aq. layers were re-extracted with hexane (10 ml). The
combined org. solns. were dried (MgSO4), filtered, and the solvent was removed in vacuo, and the residue was
dried in high vacuum to afford a colorless oil (412 mg, 99%). Chromatographic purification on silica gel (10.0 g;
40 ± 60 mm) with hexane/AcOEt 95 :5 (15 Fractions, 4.5 ml each) gave pure 2 (299 mg, 72%) as a colorless oil
from Fr. 4 ± 9. Rf (hexane/AcOEt 9 :1) 0.4. IR(CH2Cl2): 3030w, 2940s, 2860s, 2100s, 1455m, 1365m, 1260s, 1205w,
1190w, 1105s, 1030w, 910w, 8 90w, 8 20w, 670m. 1H-NMR (CDCl3, 300 MHz): 1.18± 1.63 ( m, CH2(3), CH2(4),
3
CH2(5), CH2(6), CH2(7), CH2(8) CH2(9)); 3.15 ± 3.28( m, CH2(1)), 3.28± 3.41 ( m, HÀC(2)); 3.45 (t, J ˆ 6.6,
CH2(10)), 4.49 (s, PhCH2); 7.20 ± 7.35 (m, 5 arom. H). 13C-NMR (CDCl3, 75 MHz): 8.5 (C(1)); 25.7 (C(4)); 26.1
(C(8)); 29.1, 29.1, 29.3, 29.7 (C(5, 6, 7, 9)), 34.4 (C(3)); 62.6 (C(2)); 72.8 (PhCH2); 127.4, 127.5, 128.3, 138.7
‡
(arom. C). CI-MS: 416 (0.4, [M ‡ H] ), 389 (16), 388 (100, [416 À N2]), 282 (15), 262 (10), 260 (11, [M À N2 À
‡
‡
I] ), 246 (15, [260 À CH2]), 232 (13, [246 À N]), 131 (13), 91 (34, C7H7 ). Anal. calc. for C17H26N3OI: C 49.16, H
6.31, N 10.12; found: 48.90, H 6.14, N 10.01.
1,2-Diazido-10-(benzyloxy)decane (3). In a 25-ml Schlenk-flask, fitted with a magnetic stirrer and a balloon
filled with N2, a suspension containing 2 (crude reaction product; 412 mg, 0.99 mmol) and NaN3 (97 mg,
1.5 mmol) in DMSO (1.0 ml) was stirred at r.t. for 20 h. TLC indicated a complete conversion. The colorless
suspension was transferred into a separatory funnel with hexane (20 ml) and H2O (20 ml). The org. layer was
washed with two additional portions of H2O (20 ml each), and the aq. layers were re-extracted with hexane
(10 ml). From the combined hexane solns. the solvent was removed in vacuo, and the remaining colorless oil
(315 mg, 95%, after drying in high vacuum) was purified by column chromatography (CC) on silica gel (9.0 g;
40 ± 60 mm) with hexane/AcOEt 95 :5 (15 Fractions, 9 ml each). Pure 3 was obtained from Fr. 5 ± 10 as a colorless
oil (257 mg, 78%, after drying in high vacuum). It solidified at À 208. M.p. 10 ± 158. Rf (hexane/AcOEt 9 : 1) 0.3.
IR (CH2Cl2): 3030w, 2930s, 2860s, 2100vs, 1715w, 1490w, 1445w, 1350m, 1260s, 1100s, 1030w, 915w, 660w.
1H-NMR (CDCl3, 300 MHz): 1.18± 1.70 ( m, CH2(3), CH2(4), CH2(5), CH2(6), CH2(7), CH2(8), CH2(9));
3.20 ± 3.44 (m, CH2(1), HÀC(2)); 3.46 (t, J ˆ 6, CH2(10)); 4.50 (s, PhCH2); 7.20 ± 7.40 (m, 5 arom. H). 13C-NMR
(CDCl3, 75 MHz): 25.9 (C(4)); 26.1 (C(8)); 29.2, 29.3, 29.3, 29.7 (C(5, 6, 7, 9)); 31.8 (C(3)); 54.8 (C(1)); 62.1
‡
(C(2)); 70.5 (C(10)); 72.9 (PhCH2); 127.5, 127.6, 128.3, 138.7 (arom. C). CI-MS: 331 (1, [M ‡ H] ), 330 (0.2,
‡
M ), 303 (27, [331 À N2]), 282 (21), 275 (47, [303 À N2]), 248(15), 247 (16), 246 (100, [275 À NCH3]), 170 (21),
‡
‡
154 (10), 138(10), 107 (12, [C 7H7O] ), 91 (47, C7H7 ). Anal. calc. for C17H26N6O: C 61.79, H 7.93, N 25.43; found
C 62.19, H 8.11, N 24.93.

Helvetica Chimica Acta ± Vol. 88 (2005)
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10-(Benzyloxy)decane-1,2-diamine (4). In a hydrogenation apparatus, a soln. of 3 (247 mg, 0.75 mmol) in
MeOH (10 ml) was hydrogenolyzed with Pd/C (10 % Pd, 120 mg) at r.t. for 30 min. The catalyst was removed
from the mixture by filtration through a G-4 glass filter. The residue was washed with MeOH (5 ml), and the
combined MeOH solns. were evaporated in vacuo, and the residue was dried in high vacuum for 6 h: 4 (435 mg,
80%). Colorless oil. Rf (AcOEt/MeOH/NH3 (25%) 7:3 :0.5; UV and MPA staining) 0.2. IR (CH2Cl2): 3480w,
3420w, 3030w, 2930vs, 2860s, 1715w, 1580w, 1570w, 1490w, 1450w, 1365w, 1265m, 1205w, 1100s, 1030w, 8 20w,
610w. 1H-NMR (CDCl3, 300 MHz): 1.13 ± 1.73 (m, CH2(3), CH2(4), CH2(5), CH2(6), CH2(7), CH2(8),
CH2(9)); 2.42 (dd, J ˆ 12.0, 8.0, 1 HÀC(1)); 2.55 ± 2.67 (m, J ˆ 8.0, J ˆ 3.0, 1 HÀC(2)); 2.72 (dd, J ˆ 12.0, 3.0,
1 HÀC(1)); 3.46 (t, J ˆ 6.6, CH2(10)); 4.49 (s, PhCH2); 7.20 ± 7.40 (m, 5 arom. H). 13C-NMR (CH2Cl2, 75 MHz):
26.2 (C(4)); 26.2 (C(8)); 29.4, 29.7, 29.8 (C(5, 6, 7, 9)); 35.7 (C(3)); 48.6 (C(1)); 53.6 (C(2)); 70.5 (C(10)); 72.8
‡
‡
(PhCH2); 127.4, 127.6, 128.3, 138.7 (arom. C). EI-MS: 279 (1, [M ‡ H] ), 278(0.1, M ), 249 (15, [279 À CH4N]),
‡
‡
248(93, [ M À CH4N]) , 149 (13), 91 (100, C7H7 ), 56 (12).
9,10-Diaminodecan-1-ol Dihydrochloride (5). In a hydrogenation apparatus, a soln. of 3 (247 mg,
0.75 mmol in MeOH (10 ml) was hydrogenolyzed with Pd/C (120 mg) at r.t. for 30 min. Aq. HCl (1.00n soln.;
1.5 ml, 1.5 mmol) and fresh catalyst (70 mg) were added, and hydrogenolysis was continued for 24 h at r.t. Then,
TLC indicated that starting material 3 and intermediate 4 had disappeared. The catalyst was removed from the
mixture by filtration through a G-4 glass filter. The residue was washed with MeOH (5 ml), and the combined
MeOH solns. were evaporated in vacuo, and the residue was dried in high vacuum over P2O5 for 2 days: 5
(196 mg, 100 %). Colorless solid. M.p. 125 ± 1288. Rf ((AcOEt/MeOH/NH3 (25%) 7:3 :0.5; only MPA staining)
0.1. IR (KBr): 3340m, 3160s, 3020s, 2930vs, 2850s, 1625m, 1610m, 1569m, 1532m, 1490m, 1465m, 1454m, 1405w,
1381w, 1332w, 1305w, 1193w, 1150w, 1094w, 1060s, 1040m, 1020m, 994w, 940w, 8 8 w6, 8 50w, 8 12w, 725w, 68 8w,
489w, 463w. 1H-NMR (D2O, 300 MHz): 1.14 ± 1.83 (m, CH2(2), CH2(3), CH2(4), CH2(5), CH2(6), CH2(7),
CH2(8)); 3.31 (d, J ˆ 6.3, CH2(10)); 3.47 ± 3.67 (m, 1 HÀC(9), CH2(1)). 13C-NMR (D2O, 75 MHz): 24.4 (C(7));
25.4 (C(3)); 28.5, 28.6, 28.7, 30.4, 31.6 (C(2, 4, 5, 6, 8)); 41.2 (C(10)); 49.9 (C(9)); 62.3 (C(1)).
(9,10-Diamino-1-decanol)dichloroplatinum(II) (6). In a 25-ml round-bottom flask, fitted with a magnetic
stirrer, a soln. of 5 (165 mg, 0.63 mmol) in H2O (5 ml) was heated to 658, and K2PtCl4 (262 mg, 0.63 mmol),
dissolved in H2O (2 ml) was added. Over a 15-min period, aq. NaOH soln. (1.00n; 1.10 ml, 1.10 mmol) was
added from a syringe at 658. The initially red reaction soln. (pH 2) was decolorized during this process with
simultaneous precipitation of a pale yellow solid. The mixture was not allowed to get alkaline in order to avoid
precipitation of grey-black PtO ´ H2O. At the end of the reaction, the pH was 6. The suspension was kept in an ice
bath for 10 min, and then the precipitate was separated by centrifugation. The solvent was removed by
decantation, and the yellow solid was washed twice with portions (4 ml each) of cold H2O. After drying in high
vacuum, pure 6 (228mg, 79%) was obtained. Pale yellow solid, M.p. > 2208. IR (KBr): 3450s, 3202s, 3121m,
2931s, 2857s, 1630m, 1561m, 1465m, 1460m, 1400w, 1383w, 1306w, 1266w, 1189m, 1131w, 1107w, 1055m, 1021m,
1
929w, 8 8 w2, 764m, 723w, 628w, 574m, 538m, 513m, 449m, 310m. H-NMR ((D6)DMSO, 400 MHz): 1.12 ± 1.32
(br. s, CH2(3), CH2(4), CH2(5), CH2(6), CH2(7)); 1.32 ± 1.45 (m, CH2(2)); 1.45 ± 1.60 (m, CH2(8), OH); 2.12 ±
2.45 (m, 1 HÀC(10)); 2.52 ± 2.72 (m, 1 HÀC(10)); 2.72 ± 2.95 (m, 1 HÀC(9)); 3.31 ± 3.39 (m, CH2(1)); 4.98±
5.60 (m, 2 NH2). 13C-NMR ((D6)DMSO, 100 MHz): 25.6 (C(3)); 26.1 (C(7)); 28.8, 28.9, 28.9 (C(4, 5, 6)); 30.8
(C(8)); 32.5 (C(2)); 50.8(C(10)); 59.8(C(9); 60.8(C(1)). Anal. calc. for C 10H24Cl2N2OPt: C 26.44, H 5.33, N
6.17; found: C 26.55, H 5.20, N 5.86.
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Received February 28, 2005