1
1384, 1178, 1012, 782, 682, 636 cmϪ1. H NMR (300 MHz,
(t), 29.07 (t), 29.15 (t), 29.17 (t), 29.26 (t), 29.32 (t), 29.38 (t),
29.40 (t), 29.44 (t), 29.45 (t), 29.53 (t), 31.44 (t), 31.52 (t), 31.64
(t), 31.73 (t), 31.75 (t), 31.86 (t), 31.95, 32.10, 32.24 (t), 33.18 (t),
39.64 (q), 39.68 (q), 41.75 (t), 41.90 (t), 42.05 (t), 42.40 (t), 45.36
(s), 45.50 (s), 46.89 (s), 46.97 (s), 47.59 (t), 49.84 (s), 50.04 (s),
51.59 (q), 51.61 (q), 51.69 (q), 51.73 (q), 51.82 (q), 51.86 (q),
51.93 (q), 52.03 (q), 52.06 (q), 52.29 (q), 52.41 (q), 52.43 (q),
52.58, 52.66, 52.98, 53.15, 53.26, 53.72, 54.82, 55.27, 55.62,
55.71, 59.24 (s), 59.27 (s), 64.52 (s), 65.05 (s), 74.73 (d), 74.84
(d), 77.23 (d), 87.38 (s), 87.49 (s), 98.50 (d), 106.91 (s), 107.06
(s), 109.05 (s), 163.12 (s), 163.78 (s), 165.67 (s), 166.30 (s),
167.20 (s), 168.62 (s), 170.30 (s), 170.73 (s), 171.40 (s), 171.45
(s), 171.56 (s), 171.60 (s), 172.61 (s), 172.66 (s), 172.78
(s), 172.85 (s), 173.40 (s), 173.43 (s), 173.68 (s), 174.41 (s),
176.51 (s), 176.65 (s), 176.84 (s), 177.01 (s), 177.35 (s), 177.60
(s), 192.55 (s), 193.75 (s). LSI-MS : 1367 (6, [M Ϫ ClO4Ϫ]ϩ),
CD3OD): 1.13 (d, J = 7.0 Hz, 3H), 1.20–1.43 (m, 4H), 1.44–1.60
(m, 2H), 1.70–1.88 (m, 2H), 2.60–2.75 (m, 1H), 2.78–2.97 (m,
4H), 3.62 (s, 3H), 4.01 (t, J = 7.2 Hz, 2H), 7.68 (s, 1H). 13C
NMR (75 MHz, CD3OD): 19.88 (q), 29.82 (t), 31.85 (t), 32.26
(t), 33.38 (t), 33.60 (t), 40.18 (d), 47.24 (t), 50.52 (t), 55.25 (q),
142.50 (d), 157.80 (s), 179.97 (s), 201.97 (s). EI-MS: 395 (6,
Mϩ), 363 (63), 330 (60), 316 (30), 267 (50), 248 (60), 234 (56),
220 (37), 152 (39), 113 (70), 70 (60), 42 (100), 32 (50), 28 (97).
HR-EI-MS: Calcd for C17H25N5O4S: 395.1627. Found:
395.1636. LSI-MS: 396 (100, [Mϩ1]ϩ), 268 (15).
Reaction of dimethyl methylbromomethylmalonate 4 with
heptamethyl cobester
Following the general procedure, a solution of 413 (6.4 mg,
0.027 mmol) in 1.4 ml MeOH was dropped to the green Co()
solution, which was prepared by reduction of 1 (30.4 mg, 0.027
mmol) in 10.5 ml MeOH with NaBH4 (58.7 mg, 1.6 mmol), the
color changed to brown. After work-up, the reaction mixture
was concentrated and characterized by GC and GC-MS by
comparison with reference compounds.8a GC-analysis deter-
mined the ratio 5 (tR = 5.67 min) : 6 (tR = 6.09) was 1 : 1.5.
Ϫ
1190, 1038 (100, [M Ϫ ClO4 Ϫ (CH3)(CH2)C(CO2CH3)(COS
(CH2)11CH3)]ϩ, 964 (6), 877 (7), 318 (4), 129 (8).
Reaction of O-methyl S-octadecyl 2-(bromomethyl)-2-
methylmonothiomalonate 2b with hydroxocobalamin
A solution of 2b (32.6 mg, 0.066 mmol) in 3.5 ml MeOH was
added to the green Co(I) solution, which was produced by
reduction of hydroxocobalamin (91.3 mg, 0.066 mmol) in 3 ml
MeOH with NaBH4 (144.8 mg, 3.8 mmol), the color changed
gradually to orange and remained until work-up. After CC
(hexane/ether 20:1), 3b (11.2 mg, 49%) was isolated and 2b
(5.1 mg) was recovered
Reaction of S-dodecyl O-methyl 2-(bromomethyl)-2-methyl-
monothiomalonate 2c with heptamethyl cobester in CH3CN
A solution of 2c (7.8 mg, 0.019 mmol) in 1 ml CH3CN was
added dropwise to the green Co() solution, which was prepared
by reduction of 1 (21.9 mg, 0.019 mmol) in 7.8 ml CH3CN with
NaBH4 (42.3 mg, 1.1 mmol) for 5 min; the color changed to
light brown then again to green. After stirring for 30 min, the
reaction mixture was worked up and the products were charac-
terized by GC and GC-MS by comparison with reference com-
pounds. GC analysis determined the ratio 7 (tR = 30.73 min) : 3c
(tR = 32.16 min) to be 1 : 1.
Reaction of (S )-O-methyl S-ethyl 2-(bromomethyl)-2-
methylmonothiomalonate S-2a with heptamethyl cobester
According to the general procedure: a solution of S-2e (5.1 mg,
0.019 mmol) was added to the Co() solution (from reduction of
1 (21.9 mg, 0.019 mmol) with NaBH4 (42.3 mg, 1.1 mmol)) in
7.8 ml of MeOH. The products R-3e and S-3e were character-
ized by a chiral GC-column by comparison with independently
prepared S-3e.19 The retention times S-3e (tR = 49.67 min) :
R-3e (tR = 50.68 min). The product obtained yielded a 1 : 1
mixture of S-3e and R-3e.
Reaction of S-dodecyl O-methyl 2-(bromomethyl)-2-methyl-
monothiomalonate 2c (5 molar equivalents) with heptamethyl
cobester
According to the general procedure, a solution of 2c (38.9 mg,
0.095 mmol) in 1 ml MeOH was added to the green Co() solu-
tion, which was prepared by reduction of 1 (21.9 mg, 0.019
mmol) in 7.8 ml MeOH with NaBH4 (42.3 mg, 1.1 mmol), the
color changed to orange. After work up, the reaction mixture
was submitted to FC (NaClO4 impregnated silica gel,8a hexane–
ether 8 : 1) to yield two fractions: the colored fraction was
submitted to CC (NaClO4 impregnated silica gel, CH2Cl2–
MeOH 40 : 1) and the alkylated complex 8 was isolated in 18%
yield as a mixture of two diastereoisomers. The colorless frac-
tion was characterized by GC by comparison with reference
compounds. The ratio 9 (tR = 30.53 min) : 7 (tR = 30.83 min) : 3c
(tR = 32.36 min) : 2c (tR = 35.19 min) was 1 : 3 : 10 : 14.
Reaction of S-dodecyl O-methyl 2-(bromomethyl)-2-methyl-
monothiomalonate 2c with heptamethyl cobester in CD3OD or
CH3OD
Refer to the general procedure. A solution of 2c (38.9 mg, 0.095
mmol) in 1 ml CD3OD or CH3OD was added to the green Co()
solution, which was prepared by reduction of 1 (21.9 mg, 0.019
mmol) in 7.8 ml of the corresponding deuterated solvents with
NaBH4 (42.3 mg, 1.1 mmol), the color changed to orange and
then gradually back to green. After work up, the reaction mix-
ture was characterized by GC and GC-MS by comparison with
8 Rf (CH2Cl2–MeOH 15 : 1): 0.65. UV/VIS (c = 5.5 × 10Ϫ5 M,
CH2Cl2): λmax(ε) 234 (sh, 1.06), 266 (sh, 0.91), 298 (sh, 0.87), 424
(br, 0.37). IR (CHCl3): 3030m, 2954m, 2930m, 2854w, 1732s,
1600w, 1570w, 1490m, 1470w, 1438m, 1350w, 1180m, 1150m,
1130m, 1100m, 990w, 626w. 1H NMR (300 MHz, CDCl3):
Ϫ0.07 (s, 1.8H), 0.22 (s, 1.2H), 0.34 (d, J = 6.6 Hz, 0.6H), 0.65
(d, J = 7.0 Hz, 0.4H), 0.75–2.98 (m, superimposed 1.18 (s), 1.23
(s), 1.25 (s), 1.28 (s), 1.32 (s), 1.41 (s), 1.60 (s), 1.65 (s), 1.67 (s),
1.69 (s), 1.82 (s), 2.37 (s), 2.45 (s), 2.49 (s), total 75H), 3.30–3.87
(m, superimposed 3.36 (s), 3.45 (s), 3.59 (s), 3.60 (s), 3.64 (s),
3.65 (s), 3.69 (s), 3.71 (s), 3.72 (s), 3.73 (s), 3.77 (s), 3.79 (s), 3.80
(s), total 26H), 3.87–3.98 (m, 1H), 4.01–4.11 (m, 1H), 4.65 (d,
J = 9.6 Hz)/4.71 (d, J = 9.9 Hz) (total 1H), 6.99 (s)/7.02 (s) (total
1H); 13C-NMR (75 MHz, CDCl3): 13.97 (q), 16.16 (q), 16.20
(q), 16.32 (q), 16.42 (q), 16.86 (q), 16.89 (q), 18.50 (q), 18.54 (q),
19.13 (q), 19.37 (q), 19.71 (q), 19.73 (q), 21.59 (q), 21.91 (q),
22.51 (t), 22.53 (t), 24.33 (q), 25.34 (t), 25.35 (t), 25.39 (t), 26.33
(t); 26.35 (t), 26.53 (t), 26.70 (t), 27.07 (t), 28.56 (t), 28.58 (t),
28.63 (t), 28.73 (t), 28.81 (t), 28.84 (t), 28.87 (t), 28.90 (t), 28.91
reference compounds.7/7-D (tR = 30.58 min) and 3c-D (tR
=
32.14 min) were obtained. From the reaction with 1 molar
equivalent of 1, 3c-D was isolated after FC (silica gel, hexane–
ether 8 : 1) in 97% yield. Rf (hexane–ether 20 : 1): 0.37. 1H NMR
(300 MHz, CDCl3): 0.89 (t, J = 6.6 Hz, 3H), 1.21 (s, 3H), 1.21–
1.41 (m, 18H), 1.50–1.64 (m, 2H), 2.65 (d, J = 16.2 Hz, 1H),
2.88 (t, J = 7.4 Hz, 2H), 3.00 (d, J = 16.2 Hz, 1H), 3.70 (s, 3H).
2H NMR (76.776 MHz, CCl4): 5.83 (s), reference CDCl3: 7.24.
13C-NMR (300 MHz, CDCl3): 14.10 (q), 16.69 (q), 22.68 (t),
28.81 (t), 28.97 (t), 29.10 (t), 29.33 (t), 29.47 (t), 29.50 (t), 29.56
(t), 29.61 (t), 29.62 (t), 31.90 (t), 46.78 (t), 51.93 (q), 174.87 (s),
197.63 (s). EI-MS: 300 (28), 144 (5), 130 (100), 102 (23), 60 (21),
43 (7).
Reaction of O-methyl S-octadecyl 2-(bromomethyl)-2-methyl-
monothiomalonate 2b with cobester heptamethylester reduced
electrochemically
The cathode compartment (ca. 20 ml) and the anode compart-
ment (ca. 5 ml) of the electrochemical cell were filled with
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 3 1 5 4 – 3 1 5 9
3158