DIHYDROXYLATION OF OPTICALLY ACTIVE OLEFINS
389
the two layers were clear. Upon cooling to 0°C, the formation of a precipitate
was observed, 1 mmol of the appropriate substrate was added, and
the mixture was stirred at r.t. The reaction was quenched with a sat-
urated solution of Na2S2O3, the mixture left stirring for 1 h, and then
transferred in a separative funnel. The aqueous layer was extracted
with ethyl acetate, the combined organic layers were treated with a
2N KOH solution, washed with brine until pH = 7, dried over Na2SO4,
and the solvent removed under reduced pressure.
MHz CDCl3) δ: 4.51 (1H, d, J 0.6 Hz, CHOH-CO), 4.37-4.30 (1H, m,
CH2CHOTBS), 4.23 (2H, q, J 7.2 Hz, COCH2CH3), 4.17 (1H, dd, J 0.6, 10.2
Hz, CHOH-CHOH), 3.55 (1H, dd, J 3.8, 10.2 Hz, CHN3), 3.22 (2H, bs, OH
x2), 1.72-1.46 (4H, m, CH2 x2), 1.3 (3H, t, J 7.2 Hz, COCH2CH3), 0.91 (3H,
t, J 6.6 Hz, CH2CH2CH3), 0,84 (9H, s, SiC(CH3)3), 0,07 (3H, s, SiCH3), -
0.05 (3H, s, SiCH3); 13C NMR (75 MHz CDCl3) δ: 173.3, 72.9, 71.2, 70.9,
65.4, 62.4, 34.7, 25.6, 18.7, 17.8, 14.2, 14.1, –5.0, –5.1.
(2S,3R,4R,5S)-4-Azido-5-(tert-butyl-dimethyl-silanyloxy)-2,3-
dihydroxy-octanoic acid ethyl ester (9b). Data given only for the signal
used to calculate the ratio between the two diastereomers. δH (300 MHz
CDCl3): 4.49 (1H, d, J 0.7 Hz, CHOH-CO).
Procedure C: 1 mmol of the appropriate substrate was dissolved in 10 ml
of water/tert-butanol 1:1 at r.t. and were added, in this order, 3 mmol (988
mg) of K3Fe(CN)6, 3 mmol (414 mg) of K2CO3, 0.05 mmol (39 mg) of
(DHQ)2PHAL (or (DHQD)2PHAL), 0.02 mmol (7 mg) of K2OsO4 2H2O
and 1 mmol (95 mg) of CH3SO2NH2 and the mixture left stirring
upon complete conversion of the substrate (TLC monitoring). The re-
action was quenched with a saturated solution of Na2S2O3, the mix-
ture left stirring for 1 h, and then transferred in a separative funnel.
The aqueous layer was extracted with ethyl acetate, the combined
organic layers were treated with a 2N KOH solution, washed with
brine until pH = 7, dried over Na2SO4, and the solvent removed under
reduced pressure.
Procedure D: To a solution of 1 mmol of the appropriate substrate in 9
ml of acetone/water (8:1) were added 2 mmol (270 mg) of NMO, 0.15
mmol (0,117g) of (DHQ)2PHAL (or (DHQD)2PHAL) and 0.63 ml of a
2.5% solution of OsO4 in tert-butanol (0.05 mmol of OsO4) and the mixture
left stirring overnight at r.t. The reaction was then quenched with 2.5
mmol (395 mg) of Na2S2O3, the mixture left stirring for 1 h, and then
transferred in a separative funnel. The aqueous layer was extracted with
ethyl acetate, the combined organic layers dried over Na2SO4, and the
solvent removed under reduced pressure.
(2R,3S,4S,5S)-4-Azido-5-(tert-butyl-dimethyl-silanyloxy)-2,3-
dihydroxy-octanoic ethyl ester (12a). Pale yellow oil; 1H NMR (300
MHz CDCl3) δ: 4.53 (1H, d, J 0.5 Hz, CHOH-CO), 4.31-4.24 (1H, m,
CHOH-CHOH), 4.23 (2H, q, J 7.2 Hz, COCH2CH3), 4.21-4.11 (1H, m,
CH2CHOTBS) , 3.81-3.76 (1H, m, CHN3), 3.27 (1H, bs, OH), 2.77 (1H, bs,
OH), 1.65-1.32 (4H, m, CH2 x2), 1.26 (3H, t, J 7.2 Hz, COCH2CH3), 0.92
(3H, t, J 7.3 Hz, CH2CH2CH3) 0,83 (9H, s, SiC(CH3)3), 0.03 (3H, s, SiCH3),
-0.12 (3H, s, SiCH3); 13C NMR (75 MHz CDCl3) δ: 173.8, 72.1, 70.8, 70.3,
64.1, 62.3, 36.3, 25.6, 19.2, 17.9, 14.2, 13.9, –4.8, –5.4.
(2S,3R,4S,5S)-4-Azido-5-(tert-butyl-dimethyl-silanyloxy)-2,3-
dihydroxy-octanoic ethyl ester (12b). Data given only for the signal
used to calculate the ratio between the two diastereomers. δH (300 MHz
CDCl3): 4.51 (1H, d, J 0.5 Hz, CHOH-CO).
RESULTS AND DISCUSSION
Procedure E: To a solution of 1 mmol of the appropriate substrate in 9 ml
of acetone/pH = 7 aqueous buffer (8:1) were added 2 mmol (270 mg)
of NMO, 0.15 mmol (0,117g) of (DHQ)2PHAL (or (DHQD)2PHAL),
and 0.63 ml of a 2.5% solution of OsO4 in tert-butanol (0.05 mmol of
OsO4) and the mixture left stirring overnight at r.t. The reaction
was then quenched with 2.5 mmol (395 mg) of Na2S2O3, the mixture
left stirring for 1 h, and then transferred in a separative funnel. The
aqueous layer was extracted with ethyl acetate, the combined organic
layers dried over Na2SO4, and the solvent removed under reduced
pressure.
Starting from the appropriate allylic alcohol, all substrates were
prepared in their enantiomerically enriched form, using Sharp-
less protocol for the asymmetric epoxidation (AE)17 and then fol-
lowing the procedures already described in our recent work.16
For each compound the first attempt of the AD was made
following the Sharpless procedure (procedure B) using com-
mercially available ADmix-α or ADmix-β.* However, these
conditions turned out to be unsuitable for the substrates of
choice; therefore, several variations (e.g., solvent, ligand,
etc.) were necessary in order to find the best reaction condi-
tions for each case.†
As expected, the ligand effect, when added to that of
the stereogenic center, gave in some cases a double
diastereoselection: using one chiral ligand (e.g., (DHQD)
2PHAL) it was possible to enhance the d.r. in favor of the natural
diastereomer (matched reaction), whereas the opposite chiral
ligand (e.g., (DHQ)2PHAL) was able to override intrinsic
diastereofacial preference (mismatched reaction).
(2R,3R,4S,5S)-2,3-Dihydroxy-3-(3-propyl-oxiranyl)-propionic acid
tert-butyl ester (4a). Pale yellow oil. δH (300 MHz CDCl3): 4.20–4.15
(1H, m, CHOHCO), 3.77-3.72 (1H, m, CHOH-CHOH-CO), 3.70–3.86
(2H, m, CH-O-CH), 1.58–1.40 (13H, m, CH2 x2 and (CH3)3C), 0.93 (3H,
t, J 7.3 Hz, CH2CH2CH3); δC (75 MHz CDCl3): 171.9, 83.2, 71.9, 71.4,
57.9, 57.4, 33.6, 27.0, 19.2, 13.8.
(2S,3S,4S,5S)-2,3-Dihydroxy-3-(3-propyl-oxiranyl)-propionic acid
tert-butyl ester (4b). Data given only for the signal used to calculate
the ratio between the two diastereomers. δH (300 MHz CDCl3): 4.16–
4.10 (1H, m, CHOH-CHOH-CO).
AD on Vinyl Epoxides
As shown in Table 2, the osmylation reaction on all optically
active vinyl epoxides 3–5, when carried out without ligand
(procedure A), afforded a 60:40 inseparable mixture of diols,
with a syn correlation between the ring and the diol moiety
in the main product.
Instead, using Sharpless procedure (procedure B) for the AD
of these substrates a good diastereomeric excess was obtained,
although with a very low conversion (entries 2 and 3), as it often
is for ene esters. Increasing the amount of K2OsO4, the osmium
source, and the ligands (procedure C; entries 4 and 5), after
(2R,3R,4R,5S)-4-Bromo-5-(tert-butyl-dimethyl-silanyloxy) -2,3-di
hydroxy-octanoic acid ethyl ester (7a). Orange oil; 1H NMR (300
MHz CDCl3) δ: 4.71 (1H, d, J 1.8 Hz, CHOH), 4.37–4.18 (3H, m, CHOTBS
+ COCH2CH3), 3.98-3.85 (1H, m, CHOH), 3.58 (1H, dd, J 3.2 9.9 Hz,
CHBr), 3.65–3.41 (2H, bs, 2OH), 1.82-1.41 (4H, m, CH2 x2), 1.28 (3H, t,
J 7.2 Hz, COCH2CH3), 0.83 (9H, s, SiC(CH3)3), 0.9 (3H, t, J 7.4 Hz,
CH2CH2CH3), 0.08 (3H, s, SiCH3), -0.08 (3H, s, SiCH3); 13C NMR (75
MHz CDCl3) δ: 173.0, 73.70, 73.68, 71.5, 61.8, 56.5, 35.4, 25.6, 19.3, 18.3,
14.0, 13.9, –4.8, –5.1.
(2S,3S,4R,5S)-4-Bromo-5-(tert-butyl-dimethyl-silanyloxy)-2,3-
dihydroxy-octanoic acid ethyl ester (7b). Data given only for the signal
used to calculate the ratio between the two diastereomers. δH (300 MHz
CDCl3): 3.25–3.17 (1H, m, CHBr).
*1,4g of ADmix, recommended for 1 mmol of olefin, contains: (DHQ)2PHAL
(α) or (DHQD)2PHAL (β) 0.01 mmol, potassium carbonate 3 mmol, potassium
ferricyanide 3 mmol, potassium osmate dihydrate 0.004 mmol.
†When not specified, the employment of (L*)2AQN or (L*)2PYR or L*CLB
did not produce significant diastereomeric ratios.
(2R,3S,4R,5S)-4-Azido-5-(tert-butyl-dimethyl-silanyloxy)-2,3-
dihydroxy-octanoic acid ethyl ester (9a). Pale yellow oil. 1H NMR (300
Chirality DOI 10.1002/chir