S. Raghavan, S. Nyalata / Tetrahedron xxx (2018) 1e7
5
20
CH2Cl2 (2 mL) were added (R)-O-methyl mandelic acid (8.3 mg,
0.05 mmol), DCC (12 mg, 0.06 mmol) and a few crystals of DMAP
and the mixture was stirred for 45 min. The solvent was removed
under vacuum and the residue was purified by flash column
chromatography on silica gel using 10-15% EtOAc/hexane (v/v) as
the eluent to afford ester II (15.8 mg, 0.041 mmol) in 83% yield as a
as a colourless oil; TLC: Rf 0.2 (20% EtOAc/hexane); [
a
]
D
¼ e 6.40 (c
1.0, CHCl3); IR (neat): 3421, 3067, 2933, 2859, 1746, 1590, 1467, 1427,
1106, 821 cmꢂ1 1H NMR (500 MHz, CDCl3):
; d 7.70e7.66 (m, 4H),
7.48e7.38 (m, 6H), 3.91 (dd, J ¼ 11.8, 5.5 Hz, 1H), 3.75 (dd, J ¼ 11.8,
5.3 Hz, 1H), 3.73e3.61 (m, 2H), 3.26e3.19 (m, 2H), 1.91 (t, J ¼ 6.1 Hz,
1H), 1.07 (s, 9H); 13C NMR (100 MHz, CDCl3):
d 135.5, 135.4, 132.9,
colourless oil. 1H NMR (400 MHz, CDCl3):
d
7.47e7.44 (m, 2H),
132.8, 129.9,127.8, 62.1, 60.7, 56.4, 56.2, 26.7, 19.1; MS (ESI): m/z 365
[MþNa]þ. HRMS (ESI): calcd for C20H26O3NaSi: 365.1549, found:
365.1546.
7.35e7.29 (m, 3H), 7.07 (d, J ¼ 8.7 Hz, 2H), 6.82 (d, J ¼ 8.7 Hz, 2H),
5.68 (ddd J ¼ 17.1, 10.3, 8.2 Hz, 1H), 5.09e4.96 (m, 3H), 4.77 (s, 1H),
4.24 (d, J ¼ 11.6 Hz, 1H), 4.18 (d, J ¼ 11.6 Hz, 1H), 3.80 (s, 3H), 3.42 (s,
3H), 3.40 (dd, J ¼ 10.9, 5.9 Hz, 1H), 3.36 (dd, J ¼ 10.9, 4.2 Hz, 1H),
2.60e2.48 (m, 1H), 0.96 (d, J ¼ 7.0 Hz, 3H);
4.8. (2R,3R)-3-(((tert-Butyldiphenylsilyl)oxy)methyl)oxirane-2-
carbaldehyde 12
As would be expected the olefinic signals appear upfield in ester
I in comparison to ester II while ether signals appear downfield in
ester I in comparison to ester II.
The solution of epoxy-alcohol 11 (8.5 g, 24.85 mmol) in CH2Cl2
(46 mL) was added dropwise to Dess-Martin periodinane (17.9 g,
42.24 mmol) in CH2Cl2 (92 mL) at 0OC over 5 min. The reaction
mixture was stirred at rt for 2.5 h. A mixture of aqueous saturated
NaHCO3 (68 mL) and aqueous Na2S2O3 (136 mL, 10 wt %) was added
over 5 min to the reaction mixture. The resulting mixture was
stirred for an additional 5 min, then was partitioned between ether
(450 mL) and, sequentially, aqueous saturated NaHCO3 (182 mL)
and brine (150 mL). The organic extract was dried (Na2SO4) and
concentrated. The residue was purified by flash column chroma-
tography using 10-15% EtOAc/hexane (v/v) as the eluent to afford
4.6. (Z)-4-((tert-butyldiphenylsilyl)oxy)but-2-en-1-ol 10
To a suspension of NaH (60% in Nujol, 1.2 g, 30 mmol) in anhy-
drous THF (40 mL) cooled at 0 ꢀC was added the solution of cis-2-
butene-1,4-diol 7 (2.64 g, 30 mmol) in anhydrous THF (20 mL). Af-
ter the mixture was stirred at rt for 16 h, TBDPS-Cl (7.7 mL,
30 mmol) was added and the reaction mixture was stirred at rt for
2 h. After dilution with Et2O (50 mL), the reaction mixture was
cooled to 0 ꢀC and treated with aq satd NH4Cl solution (40 mL). The
aq phase was extracted with Et2O (2 ꢁ 50 mL) and the combined
organic extracts were washed with brine (2 ꢁ 50 mL), dried over
anhydrous Na2SO4, filtered and concentrated. The residue was
purified by flash column chromatography using 15-20% EtOAc/
hexane (v/v) as the eluent to afford compound 10 (9.3 g,
28.52 mmol) in 95% yield as a colourless liquid; TLC: Rf 0.25 (20%
EtOAc/hexane); IR (neat): 3384, 2933, 2858, 1697, 1426, 1110,
the epoxy aldehyde 12 (7.43 g, 21.85 mmol) in 88% yield as a col-
20
ourless oil. TLC: Rf 0.3 (10% EtOAc/hexane); [
a]
¼ þ 52.72 (c 1.1,
D
CHCl3); IR (neat): 3071, 2858, 1723, 1427, 1110, 820 704 cmꢂ1
NMR (400 MHz, CDCl3):
;
1H
d
9.48 (d, J ¼ 4.8 Hz, 1H), 7.69e7.63 (m, 4H),
7.48e7.37 (m, 6H), 3.97 (dd, J ¼ 12.5, 3.30 Hz, 1H), 3.93 (dd, J ¼ 12.5,
4.0 Hz, 1H), 3.47e3.39 (m, 2H), 1.05 (s, 9H); 13C NMR (100 MHz,
CDCl3): d 198.0, 135.5, 132.4, 132.3, 130.0, 127.8, 60.7, 59.7, 57.6, 26.6,
19.0; MS (ESI): m/z 395 [MþNaþMeOH]þ. HRMS (ESI): calcd for
702 cmꢂ1
;
1H NMR (500 MHz, CDCl3):
d
7.70e7.67 (m, 4H),
C20H24O3NaSi: 363.1392, found: 363.1388.
7.46e7.37 (m, 6H), 5.75e5.68 (m, 1H), 5.67e5.61 (m, 1H), 4.26 (d,
J ¼ 6.0 Hz, 2H), 4.02 (d, J ¼ 6.1 Hz, 2H), 1.53e1.47 (br, 1H), 1.05 (s,
4.9. tert-Butyldiphenyl(((2R,3S)-3-vinyloxiran-2-yl)methoxy)silane
6
9H); 13C NMR (100 MHz, CDCl3):
d 135.5, 133.3, 130.7, 129.9, 129.7,
127.6, 60.1, 58.5, 26.7, 19.0; MS (ESI): m/z 327 [MþH]þ. HRMS (ESI):
calcd for C20H27O2Si: 327.1780, found: 327.1778.
To a suspension of Ph3PCH3Br (16.12 g, 45.15 mmol) in anhy-
drous THF (347 mL) was added KOtBu (4.81 g, 43.0 mmol) at 0 ꢀC.
After 30 min, a solution of the crude epoxy aldehyde 12 (7.31 g,
21.5 mmol) in anhydrous THF (63 mL) was added over 10 min at
0 ꢀC. Stirring was continued for 2 h at rt. The reaction mixture was
then partitioned between ether (100 mL), aqueous saturated
NaHCO3 (50 mL) and brine (50 mL). The organic extract was dried
(Na2SO4) and concentrated. The crude residue was purified by flash
column chromatography using 3-5% EtOAc/hexane (v/v) as the
4.7. ((2S,3R)-3-(((tert-Butyldiphenylsilyl)oxy)methyl)oxiran-2-yl)
methanol 11
To a solution of freshly distilled Ti(O-iPr)4 (8.3 mL, 28 mmol) in
dichloromethane (280 mL) was added fresh distilled (þ)-diethyl-
L-
tartrate (5.3 mL, 30.8 mmol) at ꢂ23 ꢀC. After stirring for
10 min at ꢂ23 ꢀC, a solution of compound 10 (9.13 g, 28 mmol) in
dichloromethane (16 mL) was added via dropping funnel, and the
resulting solution was stirred for 1 h at ꢂ23 ꢀC. To the above
mixture was added a TBHP (dried using molecular sieves, 5 g of 4 Å)
solution in dichloromethane (~4.0 M, 14 mL, ~56 mmol) while
maintaining the reaction temperature at about ꢂ23 ꢀC. The mixture
was stirred for 4 h at this temperature and was put in a freezer with
occasionally stirring for 10 days until the starting material was
consumed. To the light yellow reaction mixture was added aqueous
eluent to afford vinylepoxide 6 (6.9 g, 20.41 mmol) in 95% yield, as a
20
colourless oil. Rf 0.4 (3% EtOAc/hexane); [
a]
¼ þ19.77 (c 2.2,
D
CHCl3); IR (neat): 3071 2934, 2859, 1590, 1467, 1428, 1107, 820,
702 cmꢂ1 1H NMR (400 MHz, CDCl3):
;
d
7.72e7.66 (m, 4H),
7.47e7.36 (m, 6H), 5.54 (ddd, J ¼ 17.1, 10.4, 6.7 Hz, 1H), 5.39 (dd,
J ¼ 17.1, 1.1 Hz, 1H), 5.24 (dd, J ¼ 10.4, 1.1 Hz, 1H), 3.79 (dd, J ¼ 11.7,
5.6 Hz, 1H) 3.76 (dd, J ¼ 11.7, 5.0 Hz, 1H), 3.45 (dd, J ¼ 6.7, 4.4 Hz, 1H)
3.33 (dt, J ¼ 9.7, 5.3 Hz, 1H), 1.07 (s, 9H); 13C NMR (125 MHz, CDCl3):
D
-tartaric acid solution (70 mL,10%) at ꢂ23 ꢀC, then stirred for 1 h at
d 135.6, 135.5, 133.3, 133.1, 131.9, 129.7, 127.7, 120.3, 62.0, 58.4, 56.6,
this temperature and then at room temperature until the aqueous
layer became clear. After separation of the organic layer from the
aqueous layer, the organic layer was washed with water (120 mL)
and dried. The organic layer was concentrated, the residue was
dissolved in ether (220 mL), an aqueous NaOH solution (87 mL,1 M)
was slowly added at 0 ꢀC and the solution stirred for 30 min at this
temperature. The ether layer was washed with brine (100 mL),
dried over Na2SO4 and concentrated. The residue was purified by
flash column chromatography using 20-30% EtOAc/hexane (v/v) as
the eluent to afford the epoxide 11 (8.71 g, 25.46 mmol) in 91% yield
26.7, 19.2; MS (ESI): m/z 361 [MþNa]þ. HRMS (ESI): calcd for
C21H26O2NaSi: 361.1600, found: 361.1603.
4.10. (4R,6R,7R)-4-((R)-But-3-en-2-yl)-1-(4-methoxyphenyl)-
11,11-dimethyl-10,10-diphenyl-6-vinyl-2,5,9-trioxa-10-siladodecan-
7-ol 4
Redistilled BF3.OEt2 (0.150 mL, 1.25 mmol) was added to a
mixture of alcohol 5 (9.2 g, 39 mmol) and epoxide 6 (5.27 g,
15.6 mmol) in anhydrous dichloromethane (32 mL) cooled at ꢂ40
Please cite this article in press as: Raghavan S, Nyalata S, A short convergent synthesis of the [3.2.1]dioxabicyclooctane subunit of sorangicin A