U. Piarulli, P. Daubos, C. Claverie, C. Monti, C. Gennari
FULL PAPER
1
Diethyl (1S,2R)2-Phenylcyclopent-3-enyl Phosphate (6e): Yield:
CHCl
3
, 86 % enantiomeric excess). H NMR (400 MHz, CDCl
3
):
1
1
92 mg (60 %). H NMR (400 MHz, CDCl
3
): δ = 7.32–7.20 (m, 5 δ = 5.88 (dt, J = 12.0, J = 4.0 Hz, 1 H), 5.79–5.74 (m, 1 H), 4.63–
H), 5.93–5.87 (m, 1 H) 5.81–5.75 (m, 1 H), 4.83–4.78 (m, 1 H), 4.61 (m, 1 H), 4.33–4.26 (m, 1 H), 4.23–4.10 (m, 5 H), 2.25–2.20
.11–3.95 (m, 5 H), 2.88 (dd, J = 17.4, J = 5.2 Hz, 1 H), 2.59 (d, (m, 1 H), 1.87–1.77 (m, 1 H), 1.52 (s, 3 H), 1.51–1.43 (m, 1 H),
J = 17.4 Hz, 1 H), 1.26 (t, J = 7.0 Hz, 6 H) ppm. C NMR 1.48 (s, 3 H), 1.47–1.43 (m, 6 H) 0.91 (t, J = 7.4 Hz, 3 H) ppm.
4
13
1
3
(
(
1
100 MHz, CDCl
CH), 126.9 (CH), 85.3 (CH), 63.5 (2CH
6.1 (2CH
) ppm. 31P NMR (162 MHz, CDCl
IR (CHCl solution): ν˜ max. = 3035, 2897, 1581, 1520, 1477, 1423,
3
): δ = 131.7 (CH), 129.0 (CH), 128.5 (CH), 127.5
), 58.5 (CH), 39.7 (CH ), (C), 79.2 (CH), 77.6 (CH), 63.7 (2CH
): δ = –0.59 ppm. 26.1 (CH
C NMR (100 MHz, CDCl
3
): δ = 133.0 (CH), 123.6 (CH), 109.7
, JCP = 6 Hz), 28.1 (CH ),
) ppm. P NMR
): δ = –0.43 ppm. IR (film): ν˜ max. = 2986, 2935,
2
2
2
3
31
3
3
3
), 22.8 (CH
2
), 16.1 (2CH
3
), 10.7 (CH
3
3
(162 MHz, CDCl
2876, 1457, 1381, 1372, 1259, 1219, 1170, 1026, 976 cm . MS (EI,
70 eV) m/z (%) 335 (1) [M + H] , 319 (40) [M – CH
3
–1
–1
1
254, 1040, 928 cm . MS (EI, 70 eV): m/z (%) = 155 (25)
+
+
+
+
[(EtO)
2
P(O)OH + H] , 142 (100) [M – (EtO)
2
P(O)OH + H] , 127
3
] , 155 (100)
+
+
+
+
(15) [(EtO)P(O)(OH)
2
+ H] , 99 (20) [P(O)(OH)
3
+ H] . The enan- [(EtO)
2
P(O)OH + H] , 127 (55) [(EtO)P(O)(OH)
2
+ H] , 99 (25)
+
tiomeric excess of compound 6e was determined after reduction of
the phosphate ester with LiAlH in diethyl ether (quant. yield), and
derivatization of the resulting alcohol with (R)-(+)-α-Methoxy-α-
trifluoromethyl)phenylacetic acid, DCC, 4-DMAP in dichloro-
[P(O)(OH)
335.1624 [M + H] ; found: 335.1668.
3 28 6
+ H] . HRMS (EI, 70 eV) m/z calcd. for C15H O P:
+
4
Diethyl (1S,2R,5S,6S)-2-Butyl-5,6-(isopropylidenedioxy)cyclohex-3-
enyl Phosphate (11b): Yield: 59 mg (15 %). H NMR (400 MHz,
(
1
methane (quant. yield). The ratio between the two diastereomeric
Mosher esters was assessed by H NMR spectroscopy.
CDCl
H), 4.64–4.58 (m, 1 H), 4.34–4.25 (m, 1 H), 4.22–4.08 (m, 5 H),
.31–2.22 (m, 1 H), 1.83–1.18 (m, 18 H), 0.92 (t, J = 7.1 Hz, 3 H)
3
): δ = 5.85 (dt, J = 10.0, J = 3.0 Hz, 1 H), 5.79–5.74 (m, 1
1
Diethyl (1R,2R)2-Ethylcyclohex-3-enyl Phosphate (ent-7a): Yield:
2
2
5
1
67 mg (59 %). [α]
D
= –63.0 (c = 0.95, CHCl
excess). H NMR (400 MHz, CDCl ): δ = 5.71–5.64 (m, 1 H), 5.57–
.50 (m, 1 H), 4.40–4.29 (m, 1 H), 4.17–4.07 (m, 4 H), 2.26–2.01
m, 4 H), 1.87–1.76 (m, 1 H), 1.67–1.56 (m, 1 H), 1.45–1.31 (m, 7
3
, 94 % enantiomeric
13
ppm. C NMR (100 MHz, CDCl
09.7 (C), 79.6 (CH), 77.3 (CH), 78.2 (CH), 63.6 (2CH
CH), 29.7 (CH ), 28.1 (CH ), 28.0 (CH ), 26.1 (CH ), 22.7 (CH
) ppm. 31P NMR (162 MHz, CDCl
), 13.8 (CH ): δ = –
.32 ppm. IR (film): ν˜ max. = 2961, 2924, 2855, 1596, 1436, 1265,
3
): δ = 133.2 (CH), 123.4 (CH),
), 40.2
),
1
3
1
(
1
0
1
3
2
5
(
2
2
3
3
3
6.0 (2CH
3
3
3
13
H), 0.95 (t, J = 7.4 Hz, 3 H) ppm. C NMR (100 MHz, CDCl
δ = 127.8 (CH), 126.4 (CH), 77.8 (CH), 63.5 (2CH ), 43.2 (CH),
), 10.5 (CH ) ppm.
): δ = –0.47 ppm. IR (film): ν˜ max.
3
):
2
–1
145, 1022, 799 cm . HRMS (ESI) m/z calcd. for C17
85.1756 [M + Na] ; found : 385.1732.
H
31
O
6
PNa
2
7.7 (CH
P NMR (162 MHz, CDCl
2
), 25.0 (CH
2
), 23.3 (CH
2
), 16.1 (2CH
3
3
+
3
1
3
=
–1
2
964, 2873, 1655, 1515, 1465, 1250, 1022, 805 cm . MS (EI, 70 eV): Diethyl (1S,2R,5S,6S)-2-Isopropyl-5,6-(isopropylidenedioxy)cyclo-
+
+
1
m/z (%) = 262 (2) [M] , 155 (100) [(EtO)
2
P(O)OH + H] , 127 (95)
hex-3-enyl Phosphate (11c): Yield: 225 mg (60 %). H NMR
P(O)OH] , 99 (98) (400 MHz, CDCl
+
+
[(EtO)P(O)(OH)
2
+
+ H] , 108 (40) [M – (EtO)
+ H] , 79 (80) [M – (EtO)
2
3
): δ = 5.92 (dt, J = 10.0, J = 3.0 Hz, 1 H), 5.81–
+
[
P(O)(OH)
0 eV) m/z calcd. for C12
Diethyl (1R*,2S*)2-Ethylcyclohex-3-enyl Phosphate (9): Yield:
3
2
P(O)OH – Et] . HRMS (EI,
H O P: 262.1334 [M] ; found: 262.1314.
23 4
5.74 (m, 1 H), 4.64–4.57 (m, 1 H), 4.39–4.29 (m, 1 H), 4.24–4.07
(m, 5 H), 2.27–2.15 (m, 2 H), 1.55 (s, 3 H), 1.38 (s, 3 H), 1.37–1.29
+
7
(
m, 6 H), 1.04 (d, J = 6.8 Hz, 3 H), 0.86 (d, J = 6.7 Hz, 3 H) ppm.
1
3
1
C NMR (100 MHz, CDCl
C), 78.2 (CH), 78.15 (CH), 77.95 (CH), 72.9 (CH), 63.6 (CH
3.4 (CH ), 46.0 (CH), 28.0 (CH ), 26.1 (CH ), 25.4 (CH ), 20.9
(CH ), 16.1 (CH ), 16.0 (CH ):
) ppm. 31P NMR (162 MHz, CDCl
δ = 0.41 ppm. IR (film): ν˜ max. = 2961, 2924, 2850, 1635, 1274,
3
): δ = 130.3 (CH), 124.4 (CH), 109.6
2
8 mg (10 %). H NMR (400 MHz, CDCl
3
): δ = 5.71–5.64 (m, 1
(
6
2
),
H), 5.57–5.50 (m, 1 H), 4.40–4.29 (m, 1 H), 4.17–4.07 (m, 4 H),
2
1
.26–2.01 (m, 4 H), 1.87–1.76 (m, 1 H), 1.67–1.56 (m, 1 H), 1.45–
2
3
3
3
.31 (m, 7 H), 0.95 (t, J = 7.4 Hz, 3 H) ppm. 1 C NMR (100 MHz,
): δ = 127.8 (CH), 126.4 (CH), 77.8 (CH), 63.5 (2CH ), 43.2
CH), 27.7 (CH ), 25.0 (CH ), 23.3 (CH ), 16.1 (2CH ), 10.5 (CH
ppm. P NMR (162 MHz, CDCl ): δ = –0.47 ppm. IR (film): ν˜ max.
2966, 2876, 1648, 1508, 1458, 1259, 1027, 802 cm . MS (EI,
3
3
3
3
3
CDCl
(
3
2
–
1
1
29 6
029 cm . HRMS (ESI) m/z calcd. for C16H O PNa 371.1600 [M
2
2
2
3
3
)
+
31
+ Na] ; found : 371.1578.
3
–1
=
General Procedure for the Reduction of Phosphate Esters 7a and ent-
+
+
7
1
9
2
0 eV): m/z (%) = 262 (2) [M] , 155 (100) [(EtO) P(O)OH + H] ,
7
a, 8a and ent-8a, 11a-c: To a stirred solution of the phosphate
ester (0.10 mmol) in dry Et (1.66 mL), LAH (22.17 mg,
.60 mmol) was added portionwise at room temp. The solution was
+
+
2 2
27 (95) [(EtO)P(O)(OH) + H] , 108 (50) [M – (EtO) P(O)OH] ,
9 (98) [P(O)(OH) + H] ; 79 (95) [M – (EtO) P(O)OH – Et] .
3 2
2
O
+
+
0
+
23 4
HRMS (EI, 70 eV) m/z calcd. for C12H O P: 262.1334 [M] ;
found: 262.1304.
stirred for 20 min before quenching with water (SLOWLY!). The
solution was filtered through a small cotton plug and volatiles were
carefully removed under reduced pressure.
Diethyl (1R,2R)2-Ethylcyclohept-3-enyl Phosphate (ent-8a): Yield:
2
5
2
56 mg (86 %). [α]
D
= –34.0 (c = 0.95, CHCl
meric excess). H NMR (400 MHz, CDCl ): δ = 5.87 (ddt, J = 11.3,
J = 6.2, J = 1.7 Hz, 1 H), 5.47–5.38 (m, 1 H), 4.31–4.22 (m, 1 H),
3
, Ն 98 % enantio-
1
(1S,2S)-2-Ethylcyclohex-3-enol and (1R,2R)-2-Ethylcyclohex-3-enol:
Yield: Quantitative. Spectral and analytical data were in complete
agreement with the literature.[ The ee was determined by GC
on a chiral stationary phase [see General Procedures; carrier: H
(70 kPa); injector: 250 °C; detector: 250 °C; oven temperature:
3
21]
4
2
(
.15–4.05 (m, 4 H), 2.52–2.43 (m, 1 H), 2.29–2.20 (m, 1 H), 2.34–
.25 (m, 2 H), 1.98–1.87 (m, 1 H), 1.80–1.61 (m, 2 H), 1.52–1.37
2
1
3
m, 2 H), 1.36–1.29 (m, 6 H), 0.93 (t, J = 7.0 Hz, 3 H) ppm.
C
9
2
0 °C 10 min, 10 °C/min to 200 °C]. t
-ethylcyclohexen-3-ol enantiomers, 1:1), 8.4 min (1S,2S enanti-
R
= 7.9 min and 8.3 min (cis-
NMR (100 MHz, CDCl
3
): δ = 132.9 (CH), 131.0 (CH), 79.2 (CH),
), 27.9 (CH ), 24.5 (CH ), 23.0
) ppm. P NMR (162 MHz,
): δ = –0.68 ppm. IR (film): ν˜ max. = 2978, 1653, 1392, 1262,
6
3.4 (2CH
CH ), 16.1 (2CH
CDCl
2
), 45.8 (CH), 36.4 (CH
2
2
2
31
omer), 8.9 min (1R,2R enantiomer).
(
2
3
), 11.0 (CH
3
25
3
(
(
(
D
1R,2R)-2-Ethylcyclohept-3-enol: Yield: Quantitative. [α] = –41.0
–1
1
166, 1033, 997, 870 cm . MS (FAB, glycerol): m/z (%) = 277 (25)
1
c = 0.93, CHCl
400 MHz, CDCl ): δ = 5.92–5.85 (m, 1 H), 5.49–5.45 (m, 1 H),
.58–3.54 (m, 1 H), 2.36–2.28 (m, 1 H), 2.13–2.05 (m, 3 H), 1.80–
.61 (m, 3 H), 1.54–1.41 (m, 3 H), 0.96 (t, J = 7.4 Hz, 3 H) ppm.
3
, Ն 98 % enantiomeric excess). H NMR
+
+
[M + H] , 155 (100) [(EtO)
2
P(O)OH + H] , 127 (55) [(EtO)
3
+
+
P(O)(OH)
P(O)(OH)
2
+ H] , 123 (70) [M – (EtO)
2
P(O)OH + H] , 99 (85)
3
1
+
[
3
+ H] .
1
3
Diethyl (1S,2R,5S,6S)-2-Ethyl-5,6-(isopropylidenedioxy)cyclohex-3-
enyl Phosphate (11a): Yield: 188 mg (52 %). [α]
C NMR (100 MHz, CDCl
3
): δ = 133.0 (CH), 132.0 (CH), 71.3
2
5
D
= –21.0 (c = 1.3,
(CH), 47.3 (CH), 38.3 (CH
2
), 28.1 (CH ), 24.4 (CH ), 23.2 (CH ),
2
2
2
904
© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
Eur. J. Org. Chem. 2005, 895–906