Full Paper
1
28.4, 127.3, 127.2 (2 C), 126.2, 65.4, 63.0, 61.3, 50.6, 32.2, 26.0 ppm.
(R)-2-({(R)-[(R)-Cyclohex-2-en-1-yl](4-methoxyphenyl)-
+
HRMS-ESI: calcd. for C H NO [M + H] 320.2014, found 320.2014.
methyl}amino)-2-phenylethanol (2b): Pale yellow oil (63 %).
22 26
1
[
α] = +1 (c = 0.8, CH Cl ). H NMR (250 MHz, CDCl ): δ = 7.30–7.12
D
2
2
3
(
R)-2-({(S)-1-[(R)-Cyclopent-2-en-1-yl]-2-methylpropyl}amino)-2-
[
5]
(m, 5 H), 7.03 (d, J = 8.6 Hz, 2 H), 6.79 (d, J = 8.6 Hz, 2 H), 5.98 (dq,
J = 10.2, 2.1 Hz, 1 H), 5.78 (dq, J = 9.6, 3.1 Hz, 1 H), 3.80–3.74 (m, 4
H), 3.68 (t, J = 7.9 Hz, 1 H), 3.54 (dd, J = 10.3, 5.1 Hz, 1 H), 3.48 (d,
J = 8.0 Hz, 1 H), 2.47–2.28 (br. m, 3 H), 2.00–1.90 (m, 2 H), 1.70–1.59
phenylethanol (1h): Colorless oil (68 %). [α]D = +18.8 (c = 1,
CH Cl ). H NMR (250 MHz, CDCl ): δ = 7.34–7.22 (m, 5 H), 5.88 (dq,
J = 5.7, 1.9 Hz, 1 H), 5.82 (dq, J = 5.7, 2.1 Hz, 1 H), 3.83 (dd, J = 8.1,
4
1
4
6
1
2
2
3
.7 Hz, 1 H), 3.66 (dd, J = 10.5, 4.7 Hz, 1 H), 3.53 (dd, J = 10.5, 8.2 Hz,
H), 2.96–2.86 (m, 1 H), 2.47–2.21 (m, 3 H), 2.00 (dtd, J = 13.0, 8.7,
.3 Hz, 1 H), 1.77–1.64 (m, 1 H), 1.63–1.48 (m, 1 H), 0.82 (d, J =
1
3
(
(
m, 1 H), 1.52–1.38 (m, 2 H), 1.26–1.16 (m, 1 H) ppm. C NMR
63 MHz, CDCl ): δ = 158.5, 141.8, 134.7, 128.9, 128.7, 128.3, 127.3,
3
1
3
127.2, 113.5, 64.6, 64.5, 61.1, 55.2, 41.7, 26.5, 25.3, 21.4 ppm. HRMS-
.9 Hz, 3 H), 0.68 (d, J = 6.9 Hz, 3 H) ppm. C NMR (63 MHz, CDCl3):
+
ESI: calcd. for C H NO [M + H] 338.2120, found 338.2122.
22
28
2
δ = 141.9, 133.0, 131.8, 128.3, 127.5, 127.4, 66.4, 64.4, 63.6, 48.7,
1.9, 31.0, 28.5, 19.7, 17.7 ppm. HRMS-ESI: calcd. for C H NO [M +
3
1
7
26
Methyl 4-((R)-[(R)-Cyclohex-2-en-1-yl]{[(R)-2-hydroxy-1-
+
H] 260.2014, found 260.2006.
phenylethyl]amino}methyl)benzoate (2c): White solid (84 %).
1
(
R)-2-({(S)-1-[(R)-Cyclopent-2-en-1-yl]pentyl}amino)-2-phenyl-
M.p. 108 °C. [α]
D
= +5.1 (c = 1, CH
2
Cl
2
). H NMR (250 MHz, CDCl
3
):
ethanol (1i): Pale yellow oil (67 %). Isolated as a 4:1 mixture of
diastereoisomers. Major isomer: H NMR (250 MHz, CDCl ): δ = 7.40–
δ = 7.28–7.07 (m, 8 H), 7.90 (d, J = 7.9 Hz, 2 H), 5.92 (d, J = 10.2 Hz,
1 H), 5.84–5.76 (m, 1 H), 3.89 (s, 3 H), 3.76 (dd, J = 10.1, 4.1 Hz, 1
1
3
7
8
8
2
1
.21 (m, 5 H), 5.81–5.77 (m, 1 H), 5.62–5.57 (m, 1 H), 3.88 (dd, J = H), 3.67 (dd, J = 5.3, 4.2 Hz, 1 H), 3.63–3.55 (m, 2 H), 2.49–2.33 (m,
2 H), 2.00–1.90 (m, 2 H), 1.71–1.36 (m, 5 H) ppm. 13C NMR (63 MHz,
CDCl ): δ = 21.4, 25.2, 26.4, 41.7, 52.0, 62.0, 65.0, 65.4, 127.2, 127.4,
127.8, 127.9, 128.3, 128.4, 128.7, 129.4, 129.4, 141.4, 148.4,
.6, 4.6 Hz, 1 H), 3.66 (dd, J = 10.6, 4.5 Hz, 1 H), 3.47 (dd, J = 10.5,
.6 Hz, 1 H), 3.06–2.94 (m, 1 H), 2.50 (dt, J = 9.4, 4.6 Hz, 1 H), 2.36–
.29 (m, 2 H), 1.93 (dtd, J = 14.3, 8.5, 6.1 Hz, 1 H), 1.67 (ddt, J =
3.3, 8.5, 6.5 Hz, 1 H), 1.32–0.99 (m, 7 H), 0.78 (t, J = 6.8 Hz, 3 H)
3
+
166.9 ppm. HRMS-ESI: calcd. for C23
found 366.2060.
H28NO [M + H] 366.2069,
3
13
ppm. C NMR (63 MHz, CDCl ): δ = 141.7, 132.2, 131.8, 128.5, 127.4,
3
1
27.2, 66.5, 62.0, 57.8, 48.8, 32.3, 31.4, 28.2, 24.9, 22.7, 13.9 ppm.
(
R)-2-({(R)-[(R)-Cyclohex-2-en-1-yl](furan-2-yl)methyl}amino)-2-
+
HRMS-ESI: calcd. for C H NO [M + Na] 274.2171, found 274.2179.
1
8 28
phenylethanol (2d): Yellow oil (94 %). [α] = +21.8 (c = 1, CH Cl ).
D
2
2
1
(
R)-2-({(S)-2-(Benzyloxy)-1-[(R)-cyclopent-2-en-1-yl]-
H NMR (250 MHz, CDCl ): δ = 7.27–7.15 (m, 6 H), 6.18 (t, J = 2.4 Hz,
3
pentyl}amino)-2-phenylethanol (1j): Colorless oil (71 %). [α]
=
1 H), 5.98 (d, J = 3.1 Hz, 1 H), 5.91 (d, J = 10.4 Hz, 1 H), 5.78 (dq, J =
10.1, 1.8 Hz, 1 H), 3.75–3.67 (m, 2 H), 3.58–3.50 (m, 2 H), 2.54–2.44
(m, 1 H), 2.32 (br. s, 2 H), 2.02–1.92 (m, 2 H), 1.74–1.63 (m, 1 H), 1.58–
1.40 (m, 2 H), 1.35–1.20 (m, 1 H) ppm. 13C NMR (63 MHz, CDCl3):
δ = 155.4, 141.6, 141.2, 129.0, 128.4, 128.3, 127.2, 127.0, 109.6, 107.2,
65.1, 61.9, 59.2, 39.9, 26.1, 25.2, 21.4 ppm. HRMS-ESI: calcd. for
D
1
+
32.2 (c = 0.2, CH Cl ). H NMR (250 MHz, CDCl ): δ = 7.44–7.14 (m,
2 2 3
1
0 H), 5.78 (dq, J = 5.5, 2.2 Hz, 1 H), 5.60–5.54 (m, 1 H), 4.45 (s, 2
H), 3.87 (dd, J = 8.6, 4.5 Hz, 1 H), 3.65 (dd, J = 10.5, 4.5 Hz, 1 H),
.48 (dd, J = 10.5, 8.8 Hz, 1 H), 3.35 (t, J = 6.0 Hz, 2 H), 3.07–2.95
m, 1 H), 2.54–2.48 (m, 1 H), 2.40–2.23 (m, 3 H), 2.00–1.86 (m, 1 H),
3
(
1
1
3
+
.72–1.58 (m, 1 H),1.48–1.10 (m, 7 H) ppm. C NMR (63 MHz, CDCl3):
C H NO [M + H] 298.1807, found 298.1798.
19
24
2
δ = 141.5, 138.6, 132.02, 131.99, 128.5, 128.3, 127.57, 127.52, 127.47,
(
R)-2-({(R)-[(R)-Cyclohex-2-en-1-yl](pyridin-3-yl)methyl}amino)-
2-phenylethanol (2e): White solid (73 %). M.p. 99 °C. [α] = +10.5
c = 1, CH Cl ). H NMR (250 MHz, CDCl ): δ = 8.41–8.34 (m, 2 H),
1
2
3
27.2, 72.8, 70.1, 66.5, 62.1, 57.9, 48.7, 32.3, 31.5, 29.7, 24.9,
+
D
2.7 ppm. HRMS-ESI: calcd. for C H NO [M + H] 380.2590, found
2
5
34
2
1
(
7
2
2
3
80.2579.
.44 (d, J = 7.6 Hz, 1 H), 7.22–7.08 (m, 6 H), 5.90 (d, J = 10.6 Hz, 1
General Procedure for the Synthesis of Homoallylic Amines 2.
H), 5.85–5.77 (m, 1 H), 3.78–3.71 (m, 2 H), 3.65–3.56 (m, 2 H), 2.66
(br. s, 2 H), 2.53–2.42 (m, 1 H), 2.01–1.90 (m, 2 H), 1.72–1.60 (m, 1
H), 1.55–1.41 (m, 2 H), 1.26–1.11 (m, 2 H) ppm. C NMR (63 MHz,
CDCl ): δ = 149.3, 148.1, 140.9, 138.2, 134.9, 129.8, 128.4, 127.4,
127.3, 123.0, 65.6, 63.6, 63.0, 41.5, 26.2, 25.2, 21.3 ppm. HRMS-ESI:
2
Compound 2a: To a solution of 4 (112 mg, 1 mmol) and Cp ZrCl2
(322 mg, 1.02 mmol) in THF (8 mL) was added dropwise a solution
13
of nBuLi (2.5 in hexanes, 0.8 mL, 2 mmol) at 0 °C. The resulting
M
3
solution was stirred at room temperature for 3 h, then Zn(OTf)2
(
363 mg, 1 mmol) was added in one portion. The mixture was
+
calcd. for C H N O [M + H] 309.1967, found 309.1953.
20 25 2
stirred at room temperature for 1 h then cooled to –40 °C. A solu-
tion of imine (90 mg, 0.4 mmol) in THF (0.5 mL) was added, and
the mixture was stirred at –40 °C for 1 h, then slowly warmed to
room temperature over 2 h. A saturated aqueous solution of NaH-
(
R)-2-({(S,E)-1-[(R)-Cyclohex-2-en-1-yl]-3-phenylallyl}amino)-2-
phenylethanol (2f): Pale yellow oil (77 %). [α] = +39.5 (c = 1,
CH Cl ). H NMR (250 MHz, CDCl ): δ = 7.33–7.11 (m, 10 H), 6.36 (d,
D
1
2
2
3
J = 15.9 Hz, 1 H), 5.92 (dd, J = 15.9, 8.1 Hz, 1 H), 5.66–5.84 (m, 2 H),
.87 (dd, J = 6.8, 4.6 Hz, 1 H), 3.73 (dd, J = 10.7, 4.6 Hz, 1 H), 3.54
dd, J = 10.6, 6.9 Hz, 1 H), 3.20 (t, J = 7.2 Hz, 1 H), 2.36 (br. s, 1 H),
CO (5 mL) was added, and the heterogeneous mixture was vigor-
3
3
(
2
ously stirred for 30 min. The aqueous layer was extracted with Et O
2
(
2 × 5 mL), the organic phases were combined, dried with Na SO ,
2 4
1
3
.03–1.95 (m, 2 H), 1.83–1.72 (m, 1 H), 1.58–1.35 (m, 1 H) ppm.
C
filtered and concentrated under reduced pressure. The residue was
purified by column chromatography on silica gel eluting with a
mixture of PE/AcOEt to give the homoallylic amine 2a (103 mg,
NMR (63 MHz, CDCl ): δ = 141.9, 137.0, 131.4, 130.9, 129.0, 128.5,
3
1
2
3
28.4, 127.3, 127.23, 127.18, 126.2, 65.6, 63.0, 62.3, 39.8, 25.35, 25.30,
+
1.6 ppm. HRMS-ESI: calcd. for C H NO [M + H] 348.2327, found
8
9 %) as a pale yellow solid.
24 30
48.2312.
(
R)-2-({(R)-[(R)-Cyclohex-2-en-1-yl](phenyl)methyl}amino)-2-
1
phenylethanol (2a): M.p. 79 °C. [α] = +5.3 (c = 1, CH Cl ). H NMR
(R)-2-({(R,E)-1-[(R)-Cyclohex-2-en-1-yl]-2-methyl-3-phenyl-
allyl}amino)-2-phenylethanol (2g): Pale yellow solid (83 %). M.p.
70 °C. [α]D = –49.8 (c = 1, CH Cl ). H NMR (250 MHz, CDCl ): δ =
D
2
2
(
250 MHz, CDCl ): δ = 7.28–7.06 (m, 10 H), 5.99 (d, J = 10.4 Hz, 1
3
1
H), 5.79 (d, J = 9.7 Hz, 1 H), 3.77 (dd, J = 10.3, 4.5 Hz, 1 H), 3.68 (t,
J = 4.8 Hz, 1 H), 3.57–3.51 (m, 2 H), 2.46–2.40 (m, 1 H), 2.01–1.89
2
2
3
7.42–7.04 (m, 10 H), 6.29 (s, 1 H), 6.10 (d, J = 9.2 Hz, 1 H), 5.81 (d,
J = 9.9 Hz, 1 H), 3.82–3.67 (m, 2 H), 3.57 (dd, J = 11.5, 7.7 Hz, 1 H),
2.99 (d, J = 9.5 Hz, 1 H), 2.19–1.96 (m, 3 H), 1.77–1.66 (m, 1 H), 1.62–
(
m, 2 H), 1.71–1.60 (m, 1 H), 1.50–1.36 (m, 2 H), 1.27–1.15 (m, 1 H)
13
ppm. C NMR (63 MHz, CDCl ): δ = 142.7, 141.9, 129.0, 128.5, 128.4,
3
1
28.2, 127.2, 126.9, 65.3, 64.6, 61.2, 41.8, 26.6, 25.3, 21.5 ppm. HRMS-
1.24 (m, 8 H) ppm. 13C NMR (63 MHz, CDCl ): δ = 142.3, 137.8, 137.5,
3
+
ESI: calcd. for C H NO [M + H] 308.2014, found 308.2008.
128.85, 128.81, 128.6, 128.4, 128.3, 127.9, 127.3, 127.2, 126.1, 71.0,
20 26
Eur. J. Org. Chem. 2016, 2319–2327
www.eurjoc.org
2323
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim