9812
E. Fuglseth et al. / Tetrahedron 65 (2009) 9807–9813
1b starting with (R)-6b (370 mg, 2.00 mmol) from Aldrich, giving
403 mg (1.22 mmol, 61%) of (R)-1b as a colourless oil. 1H and 13C
5.17 (q, J¼8.7, 1H), 7.13(d, J¼8.2, 2H), 7.30 (d, J¼8.2, 2H), 7.51 (t, J¼7.7,
1H), 7.58 (m, 2H), 7.80 (d, J¼6.9, 1H), 7.90 (d, J¼8.2, 1H), 7.92 (m, 1H),
NMR were identical with that of rac-1b, ee: 99.5% (CHIROBIOTIC
8.06 (d, J¼8.5, 1H). 13C NMR (CDCl3)
d: 31.4 (3C), 34.4, 38.1, 58.0, 64.5
25
V2), [
a]
ꢂ56.1 (c 1.0, MeOH).
(q, J¼26.1), 123.8, 124.8, 125.2 (2C), 125.8, 126.3, 126.5, 127.3
D
(q, J¼290.7), 128.2 (2C), 129.0, 129.3, 129.6, 132.3, 134.1, 135.9, 150.0.
4.5.3. N-(4-tert-Butylbenzyl)-N-methyl-1-(naphthalen-1-yl)ethan-
amine ((S)-1b). Compound (S)-1b was synthesised as described for
1b starting with (S)-6b (370 mg, 2.00 mmol) from Aldrich, giving
467 mg (1.41 mmol, 70%) of (R)-1b as a colourless oil. 1H and 13C
NMR spectra were identical with that of rac-1b, ee: 98.5% (CHI-
19F NMR (CDCl3)
d
: ꢂ66.3 (s). HRMS (ESI): 386.2090 (calcd
C24H27F3Nþ, MþHþ, 386.2090). IR (neat, cmꢂ1): 3037, 2964, 2859.
4.5.8. 2-((4-tert-Butylbenzyl)(methyl)amino)-2-(naphthalen-1-yl)ace-
tonitrile (1g). Compound 1g was prepared as described for 1b
starting with 6g (191 mg, 0.97 mmol) and reacting for 4 h. The
product was purified by silica-gel column chromatography using
pentane/EtOAc (85/15) as eluent. This gave 250 mg (0.73 mmol, 75%)
ROBIOTIC V2), [a]
25 54.3 (c 1.0, MeOH).
D
4.5.4. N-(4-tert-Butylbenzyl)-N-methyl-1-(naphthalen-1-yl)propan-
1-amine (1c). Compound 1c was synthesised as described for 1b
starting with 6c (390 mg, 1.99 mmol). Purification by silica-gel
column chromatography (pentane/EtOAc, 9/1) gave 562 mg
of white solid, mp 75–77 ꢁC. 1H NMR (CDCl3)
d: 1.32 (s, 9H), 2.27
(s, 3H), 3.64 (d, J¼12.9,1H), 3.82 (d, J¼12.9,1H), 5.52 (s,1H), 7.25–7.29
(m, 2H), 7.34–7.38 (m, 2H), 7.44–7.52 (m, 3H), 7.82–7.87 (m, 4H). 13C
(1.63 mmol, 82%) of 1c as a colourless oil. 1H NMR (CDCl3)
d
: 0.78 (t,
NMR (CDCl3) d: 31.4 (3C), 34.6, 38.2, 59.0, 59.1, 115.3, 123.9, 124.7,
J¼7.3, 3H), 1.29 (s, 9H), 2.10 (m, 2H), 2.22 (s, 3H), 3.37 (d, J¼13.1, 1H),
3.60 (d, J¼13.1, 1H), 4.12 (m, 1H), 7.16–7.18 (m, 2H), 7.24–7.29 (m,
2H), 7.43–7.51 (m, 3H), 7.58 (d, J¼6.8, 1H), 7.74 (d, J¼8.4, 1H), 7.83–
125.4 (2C), 126.2, 126.5, 127.0, 128.7, 129.0, 129.1 (2C), 130.0, 130.9,
134.0, 134.2, 150.9. HRMS (ESI): 343.2171 (calcd C24H27Nþ2 , MþHþ,
343.2169). IR (neat, cmꢂ1): 2964, 2871, 1510, 1358, 1014, 778.
7.84 (m, 1H), 8.41 (m, 1H). 13C NMR (CDCl3)
d: 11.1, 23.5, 31.4 (3C),
34.4, 38.8, 59.0, 65.9, 124.6, 124.9 (2C), 125.0, 125.2, 125.4, 125.6,
127.4, 128.4 (2C), 128.7, 132.6, 134.2, 137.2, 137.9, 149.5. HRMS (ESI):
346.2520 (calcd C25H32Nþ, MþHþ, 346.2529). IR (neat, cmꢂ1):
2960, 2871, 2783, 1510, 1361, 1267, 776.
4.5.9. (E)-N,6,6-Trimethyl-N-(1-(naphthalen-8-yl)ethyl)hept-2-en-4-
yn-1-amine (2b). N-Methyl-1-(naphthalen-1-yl)ethanamine (6b)
(370 mg,
2.00 mmol),
N,N-diisopropylethylamine
(390 mg,
3.02 mmol) and E-1-chloro-6,6-dimethylhept-2-ene-4-yne (8)
(340 mg, 2.17 mmol) were mixed in acetonitrile (5 mL), and
refluxed under a N2 atmosphere for 2 h. The solvent was removed
at reduced pressure and dichloromethane (5 mL) was added. The
dichloromethane phase was washed with water (5 mL). The water
phase was back extracted with dichloromethane (3ꢀ5 mL). The
combined organic fractions were dried over Na2SO4, and concen-
trated under reduced pressure. The crude product was purified by
silica-gel column chromatography using pentane/EtOAc (85/15) as
eluent. This gave 370 mg (1.21 mmol, 61%) of a pale yellow oil. 1H
4.5.5. N-(4-tert-Butylbenzyl)-2-fluoro-N-methyl-1-(naphthalen-1-
yl)ethanamine (1d). N-(4-tert-Butylbenzyl)-2-fluoro-N-methyl-1-
(naphthalen-1-yl)ethanamine (1d) was prepared as described for 1b
starting with 6d (200 mg, 0.98 mmol). The product was purified by
silica-gel column chromatography using pentane/EtOAc (20/1) as
eluent. This gave 294 mg (0.84 mmol, 86%) of an oil. 1H NMR (CDCl3)
d
: 1.29 (s, 9H), 2.33 (d, J¼1.9, 3H), 3.53 (d, J¼13.4, 1H), 3.71 (d, J¼13.4,
1H), 4.56 (ddd, J¼21.0, 6.8, 3.4, 1H), 4.79 (ddd, J¼47.8, 10.0, 3.4, 1H),
5.03 (ddd, J¼47.6, 10.0, 6.8, 1H), 7.18–7.24 (m, 2H), 7.28–7.35 (m, 2H),
7.43–7.60 (m, 3H), 7.69 (d, J¼7.0,1H), 7.81 (d, J¼8.2,1H), 7.88 (m,1H),
NMR (CDCl3)
d
: 1.22 (s, 9H), 1.46 (d, J¼6.7, 3H), 2.25 (s, 3H), 2.97 (dd,
J¼14.5, 6.7, 1H), 3.16 (dd, J¼14.5, 6.2, 1H), 4.26 (q, J¼6.7, 1H), 5.58
(d, J¼15.9, 1H), 6.04 (dt, J¼15.9, 6.4, 1H), 7.37–7.52 (m, 3H), 7.56 (d,
J¼7.1, 1H), 7.73 (d, J¼8.2, 1H), 7.83 (m, 1H), 8.38 (d, J¼8.5, 1H). 13C
8.35 (d, J¼8.3, 1H). 13C NMR (CDCl3)
d: 31.4 (3C), 34.4, 39.2, 59.3
(d, J¼1.8), 65.3 (d, J¼18.7), 84.9 (d, J¼175.6), 123.9, 125.1 (2C), 125.3,
125.6, 125.7, 126.0, 128.3 (2C), 128.4, 128.9, 131.8, 134.2, 135.1
NMR (CDCl3) d: 17.8, 27.9, 31.0, 38.9, 56.8, 60.3, 77.3, 98.1, 111.9,
(d, J¼7.8), 136.5, 149.7. 19F NMR (CDCl3)
d: ꢂ213.3 (dt, J¼47.0, 20.3).
124.2, 124.4, 125.3 (2C), 125.5, 127.4, 128.7, 131.7, 134.1, 140.1, 140.7.
HRMS (ESI): 306.2212 (calcd C22H28Nþ, MþHþ, 306.2216). IR (neat,
cmꢂ1): 3053, 2964, 1443, 1192, 795 and 772.
HRMS (ESI): 350.2284 (calcd for C24H29FNþ, MþHþ, 350.2279).
IR (neat, cmꢂ1): 3045, 2964, 1508, 1197, 812 and 776.
4.5.6. N-(4-tert-Butylbenzyl)-2,2-difluoro-N-methyl-1-(naphthalen-
1-yl)ethanamine (1e). Compound 1e was prepared as described for
1b starting with 6e (448 mg, 2.02 mmol). The reaction was run for
48 h. The product was purified bysilica-gel column chromatography
using pentane/EtOAc (20/1) as eluent. This gave 660 mg (1.80 mmol,
4.5.10. (E)-N-6,6-Trimethyl-N-(1-(naphthalen-1-yl)propyl)hept-2-
en-4-yn-1-amine (2c). Compound 2c was prepared as described for
2b starting with 6c (400 mg, 2.01 mmol). The product 1f was pu-
rified by silica-gel column chromatography using pentane/EtOAc
(9/1) as eluent. This gave 350 mg (1.10 mmol, 55%) of an oil. 1H NMR
90%) of an opaque oil, which solidified at 0 ꢁC.1H NMR (CDCl3)
d: 1.29
(CDCl3)
d
: 0.67 (t, J¼7.3, 3H), 1.22 (s, 9H), 1.89–2.09 (m, 2H), 2.26
(s, 9H), 2.39 (s, 3H), 3.66 (d, J¼13.8,1H), 3.81 (d, J¼13.8,1H), 4.69 (td,
J¼12.8, 4.4, 1H), 6.69 (dt, J¼55.3, 4.4, 1H), 7.15 (d, J¼8.2, 2H), 7.28 (d,
J¼8.2, 2H), 7.48 (t, J¼7.7,1H), 7.54 (m, 2H), 7.65 (d, J¼7.1, 1H), 7.84 (d,
(s, 3H), 2.94 (ddd, J¼1.3, 6.3, 14.7, 1H), 3.14 (ddd, J¼1.3, 5.8, 14.7, 1H),
4.02 (br m, 1H), 5.55 (dt, J¼1.3, 15.6, 1H), 6.02 (ddd, J¼5.8, 6.3, 15.6,
1H), 7.40–7.50 (m, 4H), 7.74 (d, J¼8.3, 1H), 7.83–7.85 (m, 1H), 8.39–
J¼8.1, 1H), 7.88 (m, 1H), 8.20 (d, J¼8.3, 1H). 13C NMR (CDCl3)
d
: 31.3
8.40 (m, 1H). 13C NMR (CDCl3)
d: 10.8, 24.4, 27.9, 31.0 (3C), 39.3, 57.0,
(3C), 34.4, 38.8, 58.8, 65.6 (t, J¼21), 117.3 (t, J¼247.0), 124.1, 124.8,
66.8 (br), 77.3, 98.1, 111.9, 124.3, 125.0, 125.2, 125.5, 125.6, 127.4,
128.7, 132.5, 134.1, 137.8, 140.2. HRMS (ESI): 320.2377 (calcd
C23H30Nþ, MþHþ, 320.2373). IR (neat, cmꢂ1): 2966, 2870, 2785,
1509, 1361, 1264, 790, 776.
125.1 (2C), 125.7, 126.2, 126.5, 128.3 (2C), 128.8 (2C), 131.8, 132.5,
134.1, 136.1, 149.8. 19F NMR (CDCl3)
d
: ꢂ120.8 (ddd, J¼285.7, 56.2,
9.2), ꢂ123.3 (dd, J¼285.7, 56.2). HRMS (ESI): 368.2182 (calcd
C24H28F2Nþ, MþHþ, 368.2184). IR (neat, cmꢂ1): 3053, 2956, 2859.
4.5.11. (E)-N-(2-Fluoro-1-(naphthalen-1-yl)ethyl)-N-6,6-tri-
methylhept-2-en-4-yn-1-amine (2d). Compound 2d was prepared
as described for 2b starting with 6d (163 mg, 0.80 mmol). The
product 2d was purified by silica-gel column chromatography using
pentane/EtOAc (20/1) as eluent. This gave 102 mg (0.32 mmol, 41%)
4.5.7. N-(4-tert-Butylbenzyl)-2,2,2-trifluoro-N-methyl-1-(naph-
thalen-1-yl)ethanamine (1f). Compound 1f was prepared as de-
scribed for 1b starting with 6f (720 mg, 3.01 mmol) and reacting for
5 days. The product 1f was purified by silica-gel column chroma-
tography using pentane/EtOAc (9/1) as eluent. This gave 950 mg
(2.46 mmol, 82%) of an off-white solid, mp 63–65 ꢁC.1H NMR (CDCl3)
of a pale yellow oil. 1H NMR (CDCl3)
d: 1.22 (s, 9H), 2.37 (s, 3H), 3.06
(dd, J¼14.7, 6.8,1H), 3.22 (ddd, J¼14.7, 5.9,1.7,1H), 4.46 (ddd, J¼20.9,
d: 1.32 (s, 9H), 2.47 (s, 3H), 3.81 (d, J¼13.8, 1H), 3.87 (d, J¼13.8, 1H),
6.6, 3.3, 1H), 4.67 (d, 48.0, 10.1, 3.3, 1H), 4.89 (ddd, J¼47.5, 10.1, 6.6,