Chow et al.
6
-hydroxy-2,4-dimethylheptanoate (0.55 g, 2.9 mmol), was
15, 2), 139 (1), 123 (9), 111 (53), 97 (14), 85 (47), 79 (23), 69
(100), 55 (68).] The crude mesylate was displaced with cyanide
(refer to Scheme 2 for experimental details) to give nitrile 79
protected as a THP ether (0.60 g, 85%, two diastereomers)
under conditions mentioned earlier (refer to Scheme 1).
1
[
GCMS: Two GC peaks were observed. First diastereomer:
(0.13 g, 62% over two steps). [ H NMR (400 MHz, J in Hz): δ
+
m/z 171 (M - 85, 11), 139 (16), 111 (17), 101 (7), 85 (100), 69
2.66 (m, 1H), 1.82 (m, 1H), 1.28 (d, J 7.0, 3H), 0.88 (d, J 6.6,
+
13
(45), 55 (42), 41 (68). Second diastereomer: 171 (M - 85, 14),
3H), 0.86 (t, J 7.1, 3H), 0.83 (d, 6.6, 3H). C NMR (100
1
39 (21), 111 (22), 101 (8), 85 (100), 69 (54), 55 (49), 41 (79).]
MHz): δ 123.3, 43.8, 42.4, 40.3, 29.7, 28.2, 23.2, 20.1, 19.4,
+
The above ester (0.60 g, 2.2 mmol) was reduced by the LAH
protocol (refer to Scheme 1) to furnish the desired alcohol (0.50
g, 93%, two diastereomers). H NMR (400 MHz, J in Hz): δ
19.2, 18.3, 14.3. GCMS: m/z 180 (M - 1, 1), 166 (15), 152
(25), 138 (41), 124 (14), 110 (32), 96 (86), 69 (73), 55 (100).]
Nitrile 79 (0.12 g, 0.65 mmol) was then hydrolyzed under acidic
conditions (refer to Scheme 2 for details) to afford the re-
1
4
.69 (t, J 3.8, 1H), 4.59 (dd, J 5.0, 2.9, 1H), 3.90 (m, 3H), 3.77
1
(
m, 1H), 3.49-3.37 (m, 6H), 1.82-1.47 (m, 18H), 1.21 (d, J
quired methyl ester (0.11 g, 74%). H NMR (400 MHz, J in
6
0
9
3
1
.5, 3H), 1.15 (m, 2H), 1.08 (d, J 6.2, 3H), 0.88 (d, J 6.8, 6H),
.86 (d, J 6.8, 3H), 0.85 (d, J 6.5, 3H). 13C NMR (100 MHz): δ
9.5, 95.2, 72.8, 69.0, 68.9, 68.7, 62.9, 62.4, 35.7, 41.1, 40.1,
3.11, 33.09, 31.3, 31.2, 26.54, 26.47, 25.6, 25.5, 22.4, 20.1, 19.8,
Hz): δ 3.63 (s, 3H), 2.52 (s, J 7.0, 1H), 1.52-1.02 (m, 10H),
1.09 (d, J 7.0, 3H), 0.84 (t, J 7.2, 3H), 0.79 (d, J 6.2, 3H), 0.78
1
3
(d, J 6.2, 3H). C NMR (100 MHz): δ 177.7, 51.4, 44.5, 42.0,
40.2, 37.1, 29.6, 27.9, 20.0, 19.3, 19.2, 17.2, 14.3. GCMS: m/z
+
9.7, 19.6, 19.5, 16.6, 16.4. GCMS: Only one broad GC peak
214 (M , <1), 183 (1), 129 (6), 111 (3), 101 (63), 88 (100), 73
+
was observed. m/z 211 (M - 33, 1), 143 (11), 125 (5), 101 (7),
(8), 69 (30), 55 (34), 43 (67). This methyl ester is a diastereomer
of 34, which was fully characterized and described within
Scheme 2.
8
5 (100), 69 (56), 55 (62), 41 (85). This monoprotected alcohol
is a diastereomer of the fully characterized alcohol 30 described
earlier.
k. 2,4,6-Trimethylnonan-1-ol. The above methyl 2,4,6-
trimethylnonanoate (0.10 g, 0.41 mmol) was reduced to the
title alcohol in quantitative yield (83 mg, 100%) with LAH.
g. 2-(6-Iodo-1,3,5-trimethylhexyloxy)tetrahydropyran,
7. Iodination of 2,4-dimethyl-6-(tetrahydropyran-2-yloxy)-
7
1
heptan-1-ol (0.44 g, 1.8 mmol) was achieved by the procedure
H NMR (400 MHz, J in Hz): δ 3.44 (dd, J 10.4, 5.7, 1H), 3.35
described earlier (refer to Scheme 2) in obtaining iodide 77
(dd, J 10.4, 6.7, 1H), 1.89 (br s, 1H), 1.71-0.97 (m, 11H), 0.86
(d, J 6.6, 3H), 0.84 (t, J 7.2, 3H), 0.79 (d, J 6.6, 3H), 0.78 (d, J
1
(
0.62 g, 97%, two diastereomers). H NMR (400 MHz, J in
1
3
Hz): δ 4.70 (t, J 3.5, 1H), 4.59 (dd, J 5.3, 3.9, 1H), 3.88 (m,
H), 3.74 (m, 1H), 3.49 (m, 2H), 3.19 (dq, J 9.7, 4.7, 2H), 3.17
dq, J 9.7, 7.6, 2H), 1.83-1.47 (m, 20H), 1.21 (d, J 6.2, 3H),
6.5, 3H). C NMR (100 MHz): δ 68.8, 45.6, 41.4, 40.0, 33.1,
+
3
29.6, 27.1, 20.0, 19.5, 19.1, 16.4, 14.3. GCMS: m/z 153 (M -
(
33, <1), 139 (<1), 125 (17), 111 (19), 97 (12), 83 (66), 69 (62),
57 (100). This primary alcohol is a diastereomer of the one
fully characterized and described within Scheme 2.
1
.17 (m, 2H), 1.12 (m, 2H), 1.08 (d, J 5.9, 3H), 0.94 (d, J 6.5,
H), 0.93 (d, J 6.2, 3H), 0.88 (d, J 6.6, 3H), 0.86 (d, J 6.5, 3H).
C NMR (100 MHz): δ 99.9, 95.0, 73.1, 68.4, 62.9, 62.3, 45.2,
4.4, 32.01, 31.96, 31.3, 31.2, 26.8, 26.7, 25.6, 25.5, 20.5, 19.9,
3
1
3
l. Ethyl 2,4,6,8-Tetramethylundec-2-enoate. Under Swern
conditions, the above 2,4,6-trimethylnonan-1-ol (83 mg, 0.45
mmol) was oxidized to provide its aldehyde, which was then
coupled with Wittig ylide 36 (refer to Scheme 2 for details) to
4
1
9.7, 19.61, 19.58, 18.6, 18.5. GCMS: Two GC peaks were
+
observed. First diastereomer: m/z 353 (M - 1, <1), 312 (<1),
2
53 (5), 211 (3), 183 (5), 169 (9), 125 (8), 101 (6), 85 (100), 69
1
furnish the title ester (76 mg, 64% over two steps). H NMR
400 MHz, J in Hz): δ 6.51 (dq, J 10.1, 1.4, 1H), 4.16 (q, J 7.1,
H), 2.58 (m, 1H), 1.82 (d, J 1.4, 3H), 1.28 (t, J 7.1, 3H), 0.95
d, J 6.6, 3H), 0.85 (t, J 7.2, 3H), 0.80 (d, J 6.6, 3H), 0.75 (d, J
+
(
24), 55 (33). Second diastereomer: 353 (M - 1, <1), 312 (<1),
53 (7), 211 (3), 183 (5), 169 (9), 125 (7), 101 (7), 85 (100), 69
(
(
2
2
28), 55 (43). This iodide is a diastereomer of the one fully
(
described and characterized within Scheme 2.
13
6
.6, 3H). C NMR (100 MHz): δ 168.5, 148.5, 125.7, 60.4,
h. 2-(4,6-Dimethylnonan-2-yloxy)tetrahydro-2H-pyran.
Iodide 77 (0.60 g, 1.7 mmol) was alkylated under Grignard’s
conditions (refer to Scheme 2 for procedure details) to afford
45.2, 44.5, 40.4, 30.7, 29.7, 27.9, 20.1, 20.0, 19.9, 19.3, 14.4,
14.3, 12.5. GCMS: m/z 268 (M , 1), 223 (2), 183 (2), 155 (3),
+
142 (3), 127 (4), 115 (30), 102 (14), 83 (22), 69 (28), 55 (23), 43
(100), 41 (66). This unsaturated ethyl ester is a diastereomer
of 37, which was fully characterized and described within
Scheme 2.
the corresponding THP ether (0.30 g, two diastereomers) in
1
7
4
2
6
0% yield. H NMR (400 MHz, J in Hz): δ 4.72 (t, J 3.8, 1H),
.60 (dd, J 5.0, 2.6, 1H), 3.88 (m, 3H), 3.76 (m, 1H), 3.48 (m,
H), 1.84-1.01 (m, 32H), 1.21 (d, J 6.26, 3H), 1.08 (d, J 6.2,
H), 0.86 (t, J 7.0, 6H), 0.81 (d, J 6.5, 3H), 0.79 (d, J 6.5, 3H).
C NMR (100 MHz): δ 99.4, 95.0, 72.8, 68.6, 62.9, 62.1, 46.0,
5.6, 45.1, 45.0, 40.24, 40.21, 31.2, 29.69, 29.67, 26.6, 25.6, 25.5,
0.14, 20.07, 19.52, 19.50, 19.46, 19.4, 14.38, 14.36. GCMS+:
m. 2,4,6,8-Tetramethylundecan-1-ol, 66 (aaa) and 67
(
aas). The above ethyl 2,4,6,8-tetramethylundec-2-enoate (69
13
mg, 0.26 mmol) was reduced successively with Mg and LAH
refer to Scheme 2 for details) to furnish the primary alcohols
4
2
(
6
1
6 and 67 (36 mg, 61% over two steps, two diastereomers). H
NMR (400 MHz, J in Hz): δ 3.50 (dd, J 10.6, 5.3, 1H), 3.46
dd, J 10.6, 5.9, 1H), 3.38 (dd, J 10.3, 6.8, 1H), 3.35 (dd, J 10.3,
Two GC peaks were observed. First diastereomer: m/z 213 (M
-
43, <1), 198 (<1), 155 (6), 129 (3), 113 (3), 99 (9), 85 (100),
(
+
7
1 (24), 57 (30). Second diastereomer: 213 (M - 43, <1), 198
6
2
3
3
.8, 1H), 1.71 (m, 2H), 1.56 (m, 4H), 1.47 (m, 2H), 1.31 (br s,
H), 1.34-0.92 (m, 22H), 0.90 (d, J 6.8, 3H), 0.88 (d, J 6.8,
H), 0.85 (t, J 7.0, 6H), 0.83 (d, J 6.8, 3H), 0.800 (d, J 6.5,
H), 0.798 (d, J 6.5, 3H), 0.795 (d, J 6.5, 3H), 0.78 (d, J 6.5,
(
<1), 155 (4), 129 (5), 113 (2), 99 (7), 85 (100), 71 (22), 57 (31).
This THP ether is a diastereomer of the one fully characterized
and described within Scheme 2.
1
3
i. 4,6-Dimethylnonan-2-ol, 78. Deprotection of the above
THP ether (0.30 g, 1.2 mmol) was carried out under standard
conditions (refer to Scheme 1) to give alcohol 78 (0.20 g, 99%).
3H), 0.77 (d, J 6.8, 3H). C NMR (100 MHz): δ 69.1, 68.5,
45.9, 45.5, 41.3, 40.2, 40.1, 33.2, 33.0, 29.7, 29.6, 27.32, 27.27,
27.24, 27.1, 20.4, 20.07, 20.05, 19.6, 19.2, 17.1, 16.4, 14.4. This
primary alcohol is a diastereomer of 38, which was fully
characterized and described within Scheme 2.
1
H NMR (400 MHz, J in Hz): δ 3.89 (ddq, J 8.8, 6.2, 4.1, 1H),
.68 (m, 1H), 1.48 (m, 1H), 1.41 (ddd, J 13.8, 8.8, 5.0, 1H),
.33-0.97 (m, 8H), 1.17 (d, J 6.2, 3H), 0.86 (t, J 6.8, 3H), 0.85
1
1
n. 2,4,6,8-Tetramethylundecanal, 81 (aaa and aas).
Under Swern conditions, the title aldehyde was prepared from
alcohols 66 and 67 (26 mg, 0.11 mmol). The crude aldehyde
was redissolved in THF (0.5 mL) with a few 4 Å sieves and
1
3
(
d, J 6.8, 3H), 0.81 (d, J 6.8, 3H). C NMR (100 MHz): δ 65.8,
4
7.7, 45.4, 40.2, 29.7, 26.8, 24.3, 20.1, 19.4, 19.1, 14.4. GCMS:
+
m/z 157 (M - 15, 1), 139 (1), 125 (1), 112 (39), 97 (10), 85
(
60), 69 (100), 55 (69). This secondary alcohol is a diastereomer
2
purged with N , making it ready for the Wittig reaction.
of 32, which was fully characterized and described within
GCMS: Two GC peaks were observed. First diastereomer: m/z
Scheme 2.
+
1
68 (M - 57, 2), 137 (1), 123 (3), 111 (93), 99 (6), 95 (6), 85
+
j. Methyl 2,4,6-Trimethylnonanoate. Alcohol 78 (0.20 g,
(12), 71 (28), 57 (51), 43 (100). Second diastereomer: 168 (M
- 57, 2), 137 (1), 123 (4), 111 (3), 99 (7), 95 (6), 85 (13), 71
(32), 57 (52), 43 (100).
1
.2 mmol) was mesylated to yield the sulfonate ester (refer to
+
Scheme 1 for experimental details). [GCMS: m/z 154 (M
-
1826 J. Org. Chem., Vol. 70, No. 5, 2005