~
J. Pena et al. / Tetrahedron 67 (2011) 8331e8337
8336
(3H, s, OeCH3), 3.20e2.40 (2H, m, H2), 1.68e1.40 (3H, m, H3 and
H10), 1.01e0.74 (3H, t, J¼7.2 Hz, H20); dC (50 MHz; CDCl3) 200.9,
200.8, 191.5, 191.2, 145.8, 145.7, 138.5, 138.3, 134.5 (2C), 129.5 (4C),
129.2 (4C), 128.0126.7, 96.4, 96.3, 75.3, 74.1, 66.0, 65.9, 55.8(2C),
44.8, 43.3, 34.2, 33.9, 26.0, 24.4, 11.5, 11.1. EIHRMS: calcd for
C18H22O5S (MþNa): 391.1191; found: 391.1189.
4.64 (2H, s, OeCH2eO), 4.32 (2H, d, J¼6.2 Hz, H-20), 3.91 (1H, s, H6),
3.42 (1H, m, H5), 3.38 (1H, s, OeCH3) 1.26 (4H, m, H100, H200), 0.85
(3H, t, J¼6.6 Hz, H200); dC (50 MHz; CDCl3) 189.6, 144.0, 138.0, 135.0,
134.4, 131.4, 131.4, 129.3 (3C), 122.5, 96.4, 76.1, 63.6, 55.7, 36.7, 36.1,
28.7, 22.6, 14.0. EIHRMS: calcd for C13H18O5S (MþNa): 401.1399;
found: 401.1402 (MþNa).
4.3.2. (5R*,6S*,E)-5-Ethyl-2-(20-(methoxymethoxy)ethylidene)-6-
(phenylsulfonyl)cyclohex-3-enone, 7E. Compound 7E: nmax (liquid
film) 3416, 2935, 1676, 1448, 1384, 1321, 1150, 1084, 1039; dH
(400 MHz; CDCl3, HMQC, HMBC) 7.80e7.75 (2H, m, Ar), 7.60e7.45
(3H, m, Ar), 6.60 (1H, t, J¼6.0 Hz, H10), 6.45 (1H, d, J¼12.0 Hz, H3),
6.10 (1H, m, H4), 4.65 (2H, s, OeCH2eO), 4.31 (2H, d, J¼6.0 Hz, H20),
3.91 (1H, s, H6), 3.38 (3H, m, OeCH3), 3.35 (1H, m, H5), 1.45 (2H, m,
H100), 0.85 (3H, t, J¼8.0 Hz, H200); dC (100 MHz; CDCl3) 189.3, 137.8,
134.7, 134.1, 131.2, 130.7, 128.9 (4C), 122.5, 96.3, 75.6, 63.3, 55.7, 37.9,
29.1, 10.7; EIHRMS: calcd for C18H22O5S (MþNa): 373.1086; found:
373.1080. Enantiomeric ratio determined by HPLC: CHIRALCEL OD-
H column; n-hexane/isopropyl alcohol [90/10 (v/v)]; flow rate:
4.4.3. (5R*,6S*,E)-5-(3-tert-Butyldimethylsilyloxy)-2-(20-(methoxy-
methoxy)ethylidene)-6-(phenylsulfonyl)cyclohex-3-enone, 13E/13Z.
Compound 13E/13Z: nmax (liquid film) 2955, 2932, 2887, 2858, 1375,
1281, 1174, 1140, 837; dH (200 MHz; CDCl3) 7.80e7.75 (2H, m, Ar),
7.6e7.39 (3H, m, Ar), 6.62 (1H, t, J¼6.2 Hz, H10), 6.43 (1H, d,
J¼10.3 Hz, H3), 5.95e5.83 (1H, m, H4), 4.64 (2H, s, OeCH2eO), 4.31
(2H, d, J¼6.2 Hz, H20), 3.91 (1H, s, H6), 3.55 (2H, m, H200) 3.38
(OeCH3), 3.35 (1H, m, H5), 1.49 (2H, m, H100), 0.86 (9H, OeSiet-Bu),
ꢁ0.08 (6H, OeSieMe2); dC (50 MHz; CDCl3) 189.5, 138.0, 135.1,
134.5, 131.2, 131.1, 129.3 (3C), 122.7, 96.4, 76.0, 63.6, 62.5, 55.7, 36.4,
32.9, 30.0, 26.2 (3C), 18.5, ꢁ5.1 (2C). EIHRMS: calcd for C25H38O6SSi
(MþNa): 517.2056; found: 517.2059 (MþNa).
1.0 mL/min;
l¼218 nm; first peak tR¼22.4 min; second peak
tR¼24.9 min.
4.4.4. Using aldehyde 2 we were able to separate the cyclisation
products:
(5R,6S,E)-5-(1-methoxymethoxymethyl)-2-(20-methox-
4.3.3. (5R*,6S*,Z)-5-Ethyl-2-(20-(methoxymethoxy)ethylidene)-6-
(phenylsulfonyl)cyclohex-3-enone, 7Z. Compound 7Z: nmax (liquid
film) 3416, 2935, 1676, 1448, 1384, 1321, 1150, 1084, 1039; dH
(200 MHz; CDCl3) 7.85e7.75 (2H, m, Ar), 7.65 (1H, m, Ar), 7.60e7.40
(2H, m, Ar), 6.20 (1H, d, J¼10.0 Hz, H3), 6.06 (1H, t, J¼6.0 Hz, H10),
5.86 (1H, dd, J¼10.0, 6.0 Hz, H4), 4.65 (2H, s, OeCH2eO), 4.51 (1H,
ymethoxyethylidene)-6-(phenylsulfonyl)cyclohex-3-enone,
14E. Compound 14E: nmax (liquid film) 2938, 2889,1699,1448,1321,
1281, 1151, 1039; dH (400 MHz; CDCl3) 7.90e7.85 (2H, m, Ar),
7.73e7.40 (3H, m, Ar), 6.61 (1H, t, J¼8.4 Hz, H3), 6.55 (1H, d,
J¼10.0 Hz, H10), 5.93 (1H, m, H4), 4.63 (2H, s, OeCH2eO), 4.46
(OeCH2eO), 4.30 (2H, m, H20), 4.13 (1H, s, H6), 3.61 (2H, m, H100),
3.39 (1H, m, H5), 3.35 (3H, s, OeCH3), 3.22 (3H, s, OeCH3); dC
(100 MHz; CDCl3) 188.6, 137.9, 135.3, 134.5, 131.3, 128.6 (4C), 127.0,
125.0, 96.5, 96,3, 73.7, 69.1, 63.5, 55.7 (2C), 37.9. EIHRMS: calcd for
C20H26O7S (MþNa): 433.1297; found: 433.1294 (MþNa).
0
dd, J¼16.0, 6.0 Hz, H2A0), 4.43 (1H, dd, J¼16.0, 10.0 Hz, H2B ), 3.88
(1H, s, H6), 3.38 (3H, s, OeCH3), 3.35 (1H, m, H5), 1.75 (2H, m, H100),
0.65 (3H, t, J¼8.0 Hz, H200); dC (50 MHz; CDCl3) 190.8, 137.9, 134.9,
134.5, 130.9, 130.5, 129.2 (4C), 126.7, 96.5, 77.1, 67.0, 55.6, 38.6, 28.8,
9.8; EIHRMS: calcd for C18H22O5S (MþNa): 373.1086; found:
373.1080. Enantiomeric ratio determined by HPLC: CHIRALCEL OD-
H column; n-hexane/isopropyl alcohol [90/10 (v/v)]; flow rate:
4.4.5. (5R,6S,Z)-5-(1-Methoxymethoxymethyl)-2-(20-methox-
ymethoxyethylidene)-6-(phenylsulfonyl)cyclohex-3-enone,
14Z. Compound 14Z: nmax (liquid film) 2937, 2889, 1448, 1375,
1309, 1281, 1149, 1109, 1037, 918; dH (400 MHz; CDCl3) 7.90e7.85
(2H, m, Ar), 7.73e7.40 (3H, m, Ar), 6.30 (1H, d, J¼10.0 Hz, H3),
6.10 (1H, t, J¼5.2 Hz, H10), 5.80 (1H, m, H4), 4.65 (2H, s,
OeCH2eO), 4.60 (OeCH2eO), 4.60 (2H, m, H20), 4.10 (1H, s, H6),
3.65 (2H, m, H100), 3.41 (3H, s, OeCH3), 3.40 (1H, m, H5), 3.25 (3H,
s, OeCH3); dC (100 MHz; CDCl3) 189.8, 144.5, 137.9, 134.5, 130.7,
130.4, 129.3 (2C), 129.2 (2C) 124.7, 96.5(2C), 74.9, 69.1, 67,1, 55.8,
55.6, 38.4. EIHRMS: calcd for C20H26O7S (MþNa): 433.1297;
found: 433.1292 (MþNa).
1.0 mL/min;
l
¼218 nm; first peak tR¼18.3 min; second peak
tR¼19.0 min, for the rest of spectral properties see Section 4.3.3.
4.4. Typical procedure for reaction of 3 with different
aldehydes and L-proline (Table 2)
Compound 3 (50 mg, 17.6 mmol) and the corresponding alde-
hyde (17.6 mmol) were dissolved in 1 ml of isopropyl alcohol. Next,
a solution of
was added and left stirring for the appropriate time. In this case,
compounds 11e14 were isolated as 2/1 mixture of di-
L-proline (20 mol %), and additive (20 mol %) if needed,
a
astereoisomers E/Z. When mixtures, the spectral data are indicated
4.5. Typical procedure for reaction of 3 with catalysts 5b and
for the major compound.
L-proline in a tandem way (Table 3)
4.4.1. (5R*,6S*,E)-5-Propyl-2-(20-(methoxymethoxy)ethylidene)-6-
(phenylsulfonyl)cyclohex-3-enone, 11E/11Z. Compound 11E/11Z:
nmax (liquid film), 2940, 2931, 1676, 1384, 1310, 1150, 1084, 1038; dH
(200 MHz; CDCl3) 7.97e7.69 (2H, m, Ar), 7.67e7.42 (3H, m, Ar), 6.61
(1H, t, J¼6.2 Hz, H10), 6.42 (1H, d, J¼10.2 Hz, H3), 6.05 (1H, m, H4),
4.64 (2H, s, OeCH2eO), 4.32 (2H, d, J¼6.2 Hz, H20), 3.91 (1H, s, H6),
3.52e3.30 (1H, m, H5), 3.38 (3H, s, OeCH3), 1.48e1.18 (4H, m, H100,
H200), 0.87 (3H, t, J¼8.0 Hz, H-200); dC (50 MHz; CDCl3) 189.0, 142.8,
138.0, 135.0, 134.4, 131.3, 129.5 (2C), 129.3(2C), 122.6, 96.5, 76.0,
63.7, 55.6, 38.4, 20.2, 19.8, 13.9. EIHRMS: calcd for C19H24O5S
(MþNa): 387.1242; found: 387.1247 (MþNa).
Compound 3 (50 mg,17.6 mmol) and aldehyde (17.6 mmol) were
dissolved in 1 ml of CDCl3 or CHCl3. Next, catalyst 5b (20 mol %) was
added and the mixture was stirred for the specified time. When the
disappearance of the starting materials is observed by 1H NMR,
L-
proline (20 mol %), is added and the reaction continues until the
cyclic compounds are formed.
Compounds 7e14 were isolated as a 2/1 mixture of di-
astereoisomers E/Z.
Compounds 7E and 7Z, and 14E and 14Z were separated by flash
chromatography.
4.5.1. We were able to separate compounds 7E and 7Z from the
4.4.2. (5R*,6S*,E)-5-Butyl-2-(20-(methoxymethoxy)ethylidene)-6-
(phenylsulfonyl)cyclohex-3-enone, 12E/12Z. Compound 12E/12Z:
nmax (liquid film) 2957, 2932, 2872, 1281, 1138, 1124, 1097, 1043; dH
(200 MHz; CDCl3) 7.80e7.75 (2H, m, Ar), 7.60e7.49 (3H, m, Ar), 6.61
(1H, t, J¼6.2 Hz, H10), 6.42 (1H, d, J¼10.3 Hz, H3), 6.03 (1H, m, H4),
mixture:
(5R,6S,E)-5-ethyl-2-(20-(methoxymethoxy)ethylidene)-6-
(phenylsulfonyl)cyclohex-3-enone, 7E. ½a D22
ꢁ6.8 (c 0.3, CHCl3); en-
ꢃ
antiomeric ratio determined by HPLC: CHIRALCEL OD-H column; n-
hexane/isopropyl alcohol [90/10 (v/v)]; flow rate: 1.0 mL/min;
l
¼218 nm; tR (major)¼22.4 min; tR (minor)¼24.9 min, for the rest