Dihydroxylation of Polyenes
J . Org. Chem., Vol. 63, No. 21, 1998 7325
1.76-1.97 (m, 4 H), 3.50-3.66 (m, 4 H), 4.12-4.27 (m, 4 H);
13C NMR (DMSO-d6) δ 26.5, 71.6. Anal. Calcd for C8H16O4:
C, 54.53; H, 9.15. Found: C, 54.59; H, 9.20.
NMR (CDCl3) δ 1.81 (br s, 4 H), 4.87-4.99 (m, 2 H), 4.97-
5.03 (m, 2 H), 7.38-7.48 (m, 4 H), 7.48-7.58 (m, 2 H), 7.84-
7.90 (m, 4 H); 13C NMR (CDCl3) δ 21.8, 73.8, 74.9, 127.9, 131.8,
135.0; Anal. Calcd for C18H18B2O4: C, 67.57; H, 5.67. Found:
C, 67.55; H, 5.68.
Gen er a l P r oced u r e A for Dir ect Sin gle, Dou ble, or
Tr ip le Dih yd r oxyla tion /P h en ylbor on ic Ester F or m a tion .
In a round-bottomed flask under a nitrogen atmosphere,
phenylboronic acid (1.0-1.1 equiv per alkene linkage), solid
NMO (1.0-1.1 equiv per alkene linkage), and osmium tetrox-
ide (0.0020-0.0025 equiv per alkene linkage) were dissolved
in CH2Cl2. (Alternatively, osmium tetroxide may be added as
a stock solution in CH2Cl2.) The flask was immersed in a water
bath at room temperature, and the polyene (1.0 equiv) was
added as a solution in CH2Cl2 over a period of 10-15 min.
The final concentration of polyene in CH2Cl2 was generally
0.05-0.25 M depending on the scale of the reaction. The
reaction was monitored by TLC and was typically complete in
2-5 h. At reaction completion, a 10% aqueous solution of
sodium bisulfite (or sodium sulfite) was added, and the mixture
was vigorously stirred for 2 h. The two phases were separated,
and the aqueous layer was extracted twice with CH2Cl2. The
combined organic phases were dried over MgSO4, filtered, and
concentrated in vacuo, affording a solid which was recrystal-
lized from a 10:1 mixture of hexane-EtOAc unless otherwise
noted. The first case below is a representative example of this
procedure.
(1R*,2R*,4R*,5R*)-Cycloh exa n e-1,2,4,5-tetr a yl-1,2:4,5-
bis(p h en ylbor on a te) (a n ti-m eso-7c). Procedure A was
followed using 1,4-cyclohexadiene (6c) (1.48 g, 18 mmol),
phenylboronic acid (4.8 g, 40 mmol), and solid NMO (4.7 g, 40
mmol). The usual workup and recrystallization gave 4.8 g
1
(81%) of the bis(boronate) anti-meso-7c: mp 185-188 °C; H
NMR (CDCl3) δ 2.24 (m, 4 H), 4.87 (m, 4 H), 7.38-7.46 (m, 4
H), 7.52 (m, 2 H), 7.80-7.88 (m, 4 H); 13C NMR (CDCl3) δ 32.0,
73.1, 127.8, 131.6, 134.8. Anal. Calcd for C18H18B2O4: C, 67.57;
H, 5.67. Found: C, 67.56; H, 5.69.
(1R*,2R*,3R*,4R*)-Cycloh ep ta n e-1,2,3,4-tetr a yl-1,2:3,4-
bis(p h en ylbor on a te) (a n ti-r a c-7d ). Procedure A was fol-
lowed using 1,3-cycloheptadiene (6d ) (1.7 g, 18 mmol), phe-
nylboronic acid (4.8 g, 40 mmol), and solid NMO (4.7 g, 40
mmol). The usual workup and recrystallization gave 4.6 g
(75%) of the bis(boronate) anti-rac-7d : mp 128-131 °C; 1H
NMR (CDCl3) δ 1.44-1.82 (m, 4 H), 2.16-2.28 (m, 2 H), 4.57-
4.70 (m, 4 H), 7.36-7.44 (m, 4 H), 7.50 (m, 2 H), 7.88-7.94
(m, 4 H); 13C NMR (CDCl3) δ 18.4, 28.6, 77.5, 81.3, 127.7, 131.5,
135.0. Anal. Calcd for
Found: C, 67.93; H, 5.96.
C19H20B2O4: C, 68.33; H, 6.04.
(1R*,2R*,5R*,6R*,9R*,10R*)-Cyclod od eca n e-1,2,5,6,9,-
10-h exa yl-1,2:5,6:9,10-tr is(p h en ylbor on a te) (r a c-4). Phe-
nylboronic acid (11.9 g, 97.7 mmol), solid NMO (11.4 g, 97.7
mmol), and CH2Cl2 (75 mL) were added to a 500 mL round-
bottomed flask under a nitrogen atmosphere. After dissolution
of the solids, osmium tetroxide (47 mg, 0.186 mmol, 0.6 mol
%) was added as a solid. The flask was immersed in a water
bath at room temperature, and the triene 1 (5.0 g, 31.0 mmol)
in CH2Cl2 (75 mL) was added over a period of 15 min. After
5 h, the reaction was complete (TLC, 4:1 hexane-EtOAc). A
10% aqueous solution of sodium sulfite (75 mL) was added,
and the two-phase mixture was stirred for an additional 2 h.
The layers were separated, and the aqueous layer was
extracted with CH2Cl2 (2 × 150 mL). The combined organic
phases were washed with 2 N HCl (100 mL), dried over
MgSO4, filtered, and concentrated in vacuo. The crude ratio
of diastereomers was determined to be ca. 1:1 by 1H NMR.
For purification, acetone (100 mL) was added to the crude
residue, and the resulting slurry was refluxed with stirring
for 5 min. The mixture was cooled, and the white precipitate
was collected by filtration. This trituration procedure was
then repeated on the resulting solid product and gave 5.6 g
(35%) of the pure D3-isomer rac-4: mp 226 °C; 1H NMR
(CDCl3) δ 1.75-1.87 (m, 6 H), 2.15-2.25 (m, 6 H), 4.25 (br s,
6 H), 7.37-7.43 (m, 6 H), 7.47-7.52 (m, 3 H), 7.80-7.85 (m, 6
H); 13C NMR (CDCl3) δ 30.7, 83.1, 127.8, 131.6, 134.8; HRMS
(FAB+/NBA) calcd for C30H33B3O6 (MNa+) m/e 545.2454, found
m/e 545.2469.
(1R*,2R*,3R*,4R*)-Cyclop en ta n e-1,2,3,4-tetr a yl-1,2:3,4-
bis(p h en ylbor on a te) (a n ti-r a c-7a ). Procedure A was fol-
lowed using freshly distilled cyclopentadiene (6a ) (2.4 g, 36
mmol), phenylboronic acid (9.2 g, 76 mmol), and solid NMO
(8.9 g, 76 mmol). The usual workup and recrystallization gave
7.5 g (68%) of the bis(boronate) anti-rac-7a : mp 140-142 °C;
1H NMR (CDCl3) δ 2.51 (t, J ) 5.6 Hz, 2 H), 5.03 (d, J ) 6.3
Hz, 2 H), 5.17 (q, J ) 5.8 Hz, 2 H), 7.36-7.43 (m, 4 H), 7.50
(m, 2 H), 7.79-7.84 (m, 4 H); 13C NMR (CDCl3) δ 42.3, 81.1,
87.5, 127.9, 131.8, 134.9. Anal. Calcd for C17H16B2O4: C,
66.74; H, 5.27. Found: C, 66.67; H, 5.37.
(1R*,2R*,3R*,4R*)-Cycloh exa n e-1,2,3,4-tetr a yl-1,2:3,4-
bis(p h en ylbor on a te) (a n ti-r a c-7b). Procedure A was fol-
lowed using 1,3-cyclohexadiene (6b) (4.0 g, 50 mmol), phenyl-
boronic acid (12.7 g, 105 mmol), and solid NMO (12.3 g, 105
mmol). The usual workup and recrystallization gave 13.0 g
(81%) of the bis(boronate) anti-rac-7b: mp 161-163 °C; 1H
(1R*,2R*,3R*,4R*)-Cyclooct a n e-1,2,3,4-t et r a yl-1,2:3,4-
bis(p h en ylbor on a te) (a n ti-r a c-7e). Procedure A was fol-
lowed using 1,3-cyclooctadiene (6e) (2.0 g, 18 mmol), phenyl-
boronic acid (4.7 g, 40 mmol), and solid NMO (4.8 g, 40 mmol).
The usual workup and recrystallization gave 5.8 g (85%) of
the bis(boronate) anti-rac-7e: mp 112-113 °C; 1H NMR
(CDCl3) δ 1.40-1.75 (m, 4 H), 1.77-1.94 (m, 2 H), 2.15-2.32
(m, 2 H), 4.61-4.75 (m, 4 H), 7.36-7.45 (m, 4 H), 7.50 (m, 2
H), 7.88-7.95 (m, 4 H); 13C NMR (CDCl3) δ 24.6, 29.7, 79.6,
80.1, 127.8, 131.6, 135.0; Anal. Calcd for C20H22B2O4: C, 69.03;
H, 6.37. Found: C, 69.14; H, 6.44.
(2R*,3S*,5S*,8R*)-2-Meth ylbicyclo[2.2.1]h eptan e-2,3,5,8-
tetr a yl-2,3:5,8-bis(p h en ylbor on a te) (r a c-7f). Procedure A
was followed using 5-methylene-2-norbornene (6f) (1.9 g, 18
mmol), phenylboronic acid (4.5 g, 37 mmol), and solid NMO
(4.5 g, 38 mmol). The usual workup and recrystallization gave
4.6 g (74%) of the bis(boronate) rac-7f: mp 120-121 °C; 1H
NMR (CDCl3) δ 1.43 (dd, J ) 14.2, 2.5 Hz, 1 H), 1.79-1.83
(m, 1 H), 2.09-2.14 (m, 2 H), 2.52 (s, 1 H), 2.57 (d, J ) 5.3 Hz,
1 H), 4.16 (d, J ) 9.3 Hz, 1 H), 4.46-4.52 (m, 3 H), 7.36-7.42
(m, 4 H), 7.47-7.51 (m, 2 H), 7.79-7.82 (m, 4 H); 13C NMR
(CDCl3) δ 30.1, 41.7, 42.6, 52.6, 72.6, 79.1, 83.3, 85.6, 127.8,
131.5, 131.6, 134.8, 135.0. Anal. Calcd for C20H20B2O4: C,
69.43; H, 5.83. Found: C, 69.51; H, 5.90.
(1R*,2S*,5S*,6R*)-Cyclooct a n e-1,2,5,6-t et r a yl-1,2:5,6-
bis(ph en ylbor on ate) (a n ti-meso-10) an d (1R*,2S*,5R*,6S*)-
Cyclooct a n e-1,2,5,6-t et r a yl-1,2:5,6-b is(p h en ylb or on a t e)
(syn -m eso-11). Procedure A was followed using 1,5-cyclooc-
tadiene (8) (2.08 g, 19.2 mmol), phenylboronic acid (5.16 g, 42.3
mmol), and solid NMO (4.96 g, 42.3 mmol). The usual workup
gave a solid which showed a ca. 1:1 ratio of isomers by 1H
NMR. Recrystallization of the crude mixture from hexanes-
EtOAc (250 mL, 4:1) gave 2.25 g (34%) of the bis(boronate)
anti-meso-10: mp 214-215 °C; 1H NMR (CDCl3) δ 1.50-1.65
(m, 4 H), 2.18-2.26 (m, 4 H), 4.65-4.76 (m, 4 H), 7.34-7.43
(m, 4 H), 7.49 (m, 2 H), 7.76-7.82 (m, 4 H); 13C NMR (CDCl3)
δ 25.4, 80.0, 127.8, 131.5, 134.8. Anal. Calcd for C20H22B2O4:
C, 69.03; H, 6.37. Found: C, 68.98; H, 6.49. The other isomer
syn-meso-11 was obtained by column chromatography of the
mother liquor (1:1 hexanes-Et2O) followed by recrystallization
(10:1 hexanes-EtOAc), giving 1.67 g (25%) of syn-meso-11: mp
157-159 °C; 1H NMR (CDCl3) δ 1.75-1.92 (m, 4 H), 2.02-
2.20 (m, 4 H), 4.66-4.74 (m, 4 H), 7.32-7.40 (m, 4 H), 7.46
(m, 2 H), 7.75-7.81 (m, 4 H); 13C NMR (CDCl3) δ 24.6, 79.0,
127.8, 131.5, 134.8. Anal. Calcd for C20H22B2O4: C, 69.03; H,
6.37. Found: C, 69.04; H, 6.47.
(23) Powell, K. A.; Hughes, H.; Katchian, J . F.; J erauld, J . F.; Sable,
H. Z. Tetrahedron 1972, 28, 2019. The syn/anti stereochemistry issue
for the tetrol was not resolved. According to our results, they prepared
the syn isomer, (1R*,2S*,5R*,6S*)-cyclooctane-1,2,5,6-tetrol.
Authentic syn-meso-11 was also prepared by refluxing a
mixture of phenylboronic acid (2.42 g, 20 mmol) and (1R*,
2S*,5R*,6S*)-cyclooctane-1,2,5,6-tetrol (syn-meso-9) (1.76 g, 10