Towards the Synthesis of Restricted Analogues of Peloruside A
oxybenzyloxy)hex-3-enyloxy](tert-butyl)diphenylsilane (25): At
room temperature under argon, 2,2-dimethoxypropane (2,2-DMP;
166 mg, 1.59 mmol, 10 equiv.) followed by pyridinium p-toluene-
sulfonate (PPTS; 40 mg, 0.159 mmol, 1 equiv.) were added to diol
24 (118 mg, 0.159 mmol, 1 equiv.) dissolved in dry CH2Cl2. The
resulting mixture was then stirred for 14 h at the same temperature.
After this time the solvent was evaporated and the crude mixture
was subjected to column chromatography on silica gel (PE/Et2O,
98:2 to 80:20) to give pure diastereomer 25 (101 mg, 81%) as a
H, CH(OH)CH2 and CH2(CH–O–acetonide)2 and CH2CH3], 1.50–
1.00 [m, 8 H, CH2(CH–O–acetonide)2 and CH2 CH3 and
CH2CH2CH2], 1.40 (s, 3 H, CH3), 1.37 (s, 3 H, CH3), 1.21 (s, 9 H,
tBu), 0.87 (s, 3 H, CH3), 0.84 (s, 3 H, CH3), 0.80 (t, J = 7.5 Hz, 3
H, CH2CH3) ppm. 13C NMR (100 MHz, C6D6): δ = 136.2 (Car),
135.9 (CH2CH), 135.8 (CHCH), 134.0 (C(IV)ar), 133.6 (CHCH),
130.0 (Car), 116.6 (CH2CH), 100.7 (C(IV) acetonide), 80.0 [C(Me)2-
CH–O], 77.8 (CH2CHCH2CH–O), 68.6 (CHOH), 67.8 [C(Me)2-
CH–O–acetonide] 67.2 (CH2OTBDPS), 67.0 (CH–O–acetonide),
43.8 [CH(OH)CH2], 42.7 (CHEt), 41.7 (CH2CHCH2), 40.4 (C(IV)
1
colorless oil. [α]2D0 = –44.4 (c = 1.0, C HCl3). H NMR (400 MHz,
C6D6): δ = 7.82–7.79 (m, 4 H, Har), 7.30–7.28 (m, 2 H, Har), 7.26– acetonide), 34.1 [CH2(CH–O–acetonide)2], 31.5 (CH2CH2CH2),
7.21 (m, 6 H, Har), 6.83–6.81 (m, 2 H, Har), 5.97–5.87 (m, 1 H, 27.2 (tBu), 25.2 (CH3), 25.1 (CH2CH2CH2), 24.8 (CH2CH3), 24.4
CH2=CH), 5.59 (dd, J = 9.4, J = 11.0 Hz, 1 H, CHCH), 5.45 (t, J
= 11.0 Hz, 1 H, CHCH), 5.05–5.00 (m, 2 H, CH2=CH), 4.57 and
(CH3), 24.3 (CH2CH2CH2), 19.5 (C(IV) tBu), 17.8 (CH3), 17.1
(CH3), 12.0 (CH2CH3) ppm. HRMS: calcd. for C41H62O5SiNa [M
4.24 (AB system, J = 11.4 Hz, 2 H, CH2OPMB), 4.44–4.38 (m, 1 + Na+] 685.4259; found 685.4282.
H, CHOPMB), 4.32 [dd, J = 4.0, J = 6.2 Hz, 1 H, C(Me)2CH–O–
To a solution of the previous alcohol (67 mg, 0.1 mmol, 1 equiv.)
acetonide], 4.28–4.24 (m, 1 H, CH–O–acetonide), 3.74–3.65 (m, 2
H, CH2OTBDPS), 3.45 [dd, J = 1.5, J = 11.0 Hz, 1 H, C(Me)2CH–
O], 3.26–3.19 (m, 1 H, CH2CHCH2CH–O), 2.70–2.61 (m, 1 H,
CHEt) 2.35–2.28 [m, 2 H, CH2 (CH–O–acetonide)2 and
CH2CHCH2], 2.19–2.13 (m, 1 H, CH2CHCH2), 1.90–1.72 [m, 4 H,
CH2CH3 and CH2(CH–O–acetonide)2 and CH2CHOPMB], 1.51
(s, 3 H, CH3), 1.48 (s, 3 H, CH3), 1.40–1.10 (m, 7 H, CH2CH2CH2
and CH2CHOPMB), 0.94 (s, 3 H, CH3), 0.91 (s, 3 H, CH3), 0.86
(t, J = 7.5 Hz, 3 H, CH2CH3) ppm. 13C NMR (100 MHz, C6D6):
δ = 159.6 (C(IV)ar), 136.1 (Car), 135.8 (CH2CH), 134.6 (CHCH),
134.2 (C(IV)ar), 133.0 (CHCH), 131.8 (C(IV)ar), 130.1 (Car), 129.6
(Car), 128.7 (C(IV)ar), 128.3 (Car), 116.4 (CH2CH), 114.1 (Car), 100.5
(C(IV) acetonide), 80.3 [C(Me)2CH–O], 77.8 (CH2CHCH2CH–O),
71.5 (CHOPMB), 70.0 (CH2Ar), 68.6 [C(Me)2CH–O–acetonide],
67.6 (CH2OTBDPS), 64.7 (CH–O–acetonide), 54.8 (OCH3), 43.3
(CH2CHOPMB), 42.3 (CHEt), 41.7 (CH2CHCH2), 40.5 [C(Me)2],
33.8 [CH2(CH–O–acetonide)2], 31.6 (CH2CH2CH2), 27.2 (C(IV)
tBu), 25.4 (CH3), 25.3 (CH2CH2CH2), 25.0 (CH2CH3), 24.8 (CH3),
24.4 (CH2CH2CH2), 19.6 (C(IV) tBu), 18.0 (CH3), 17.3 (CH3), 12.0
(CH2CH3) ppm. MS (CI): m/z = 783 [M + H]+. HRMS: calcd. for
C49H70O6SiNa [M + Na+] 805.4834; found 805.4845.
and Hünig’s base (70 μL, 0.4 mmol, 4 equiv.) in CH2Cl2 (1 mL) at
0 °C under argon atmosphere was added acryloyl chloride (16 μL,
0.2 mol, 2 equiv.). The mixture was stirred for 4 h at room tempera-
ture and quenched with a saturated aqueous solution of ammo-
nium chloride (2 mL). The aqueous layer was extracted with
CH2Cl2 (3ϫ 10 mL) and the combined organic layers were washed
with brine, dried with anhydrous MgSO4, filtered and concentrated
under reduced pressure. The resulting residue was subjected to col-
umn chromatography on silica gel (PE/Et2O, 99:1 to 90:10) to af-
ford expected acrylate 26 (68 mg, 95%). [α]2D0 = –25.1 (c = 1.25,
1
CHCl3). H NMR (300 MHz, C6D6): δ = 7.84–7.79 (m, 4 H, Har),
7.30–7.22 (m, 6 H, Har), 6.28 (dd, J = 1.6, J = 17.2 Hz, 1 H,
CH2CHCO), 6.14–6.10 [m, 1 H, CHO(CO)], 6.00–5.85 (m, 2 H,
2ϫ CH2CH), 5.61 (dd, J = 1.6, J = 9.2 Hz, 1 H, CHCH), 5.45 (t,
J = 10.4 Hz, 1 H, CHCH), 5.24 (dd, J = 1.6, J = 10.4 Hz, 1 H,
CH2CHCO), 5.06–5.02 (m, 2 H, CH2CH), 4.26 [dd, J = 6.4, J =
10.4 Hz, 1 H, C(Me)2CH–O–acetonide], 4.05–3.98 (m, 1 H, CH–
O–acetonide), 3.76 (dd, J = 4.8, J = 9.8 Hz, 1 H, CH2OTBDPS),
3.69 (dd, J = 5.6, J = 9.8 Hz, 1 H, CH2OTBDPS), 3.42 [dd, J =
1.6, J = 11.2 Hz, 1 H, C(Me)2CH–O], 3.26–3.20 (m, 1 H,
CH2CHCH2CH–O), 2.95–2.86 (m, 1 H, CHEt), 2.35–2.28 (m, 1 H,
CH2CHCH2), 2.24–2.13 [m, 2 H, m, 1 H, CH2CHCH2 and
CH2(CH–O–acetonide)2], 1.90–1.66 [m, 4 H, CH2(CH–O–aceton-
ide)2 and CH2CHOCO and CH2CH3], 1.47 (s, 3 H, CH3), 1.43 (s,
3 H, CH3), 1.41–1.05 (m, 7 H, CH2CH2CH2 and CH2CH3), 1.19
(s, 9 H, tBu), 0.89 (s, 3 H, CH3), 0.88 (s, 3 H, CH3), 0.84 (t, J =
7.5 Hz, 3 H, CH2CH3) ppm. 13C NMR (75 MHz, C6D6): δ = 165.0
(CO), 136.3 (CHCH), 136.2 Car, 135.8 (CH2CH), 134.4 (Car), 129.9
(CH2CHCO), 129.8 Car, 129.6 (CHCH), 129.4 (CH2CHCO), 116.5
(CH2CHCH2), 100.6 (C(IV) acetonide), 80.2 [C(Me)2CH–O], 77.8
(CH2CHCH2CH–O), 68.5 [CHO(CO)], 68.3 [C(Me)2CH–O–acet-
onide], 67.2 (CH2OTBDPS), 64.8 (CH–O–acetonide), 42.5
[CH2(CH–O–acetonide)2], 42.2 (CHEt), 41.7 (CH2CHCH2), 40.4
(C(IV)), 34.0 [CH2(CH–O–acetonide)2], 31.6 (CH2CH2CH2), 27.2
(tBu), 25.3 (CH2CH3), 25.2 (CH2CH2CH2), 24.8 (CH3), 24.7
(CH3), 24.3 (CH2CH2CH2), 19.7 (C(IV)), 17.9 (CH3), 17.2 (CH3),
11.9 (CH2CH3) ppm. HRMS: calcd. for C44H64O6SiNa [M + Na+]
739.4370; found 739.4359.
(2S,5R,Z)-1-((4R,6S)-6-{2-[(2S,6R)-6-Allyl-tetrahydro-2H-pyran-
2-yl]propan-2-yl}-2,2-dimethyl-1,3-dioxan-4-yl)-5-[(tert-butyldi-
phenylsilyloxy)methyl]hept-3-en-2-ylacrylate (26): To a cold solu-
tion of acetonide 25 (205 mg, 0.262 mmol, 1 equiv.) in CH2Cl2
(2.4 mL) and phosphate buffer (pH = 7.0, 1.2 mL) was added DDQ
(71 mg, 0.313 mmol, 1.2 equiv.). The reaction mixture was stirred
for 2.5 h at 0 °C before a second addition of DDQ (30 mg,
0.132 mmol, 0.5 equiv.) and the mixture was stirred for a further
1 h. The reaction was diluted with CH2Cl2 (3 mL) quenched with
saturated aqueous NaHCO3 solution (3 mL), and diluted with
water. The layers were separated and the aqueous layer extracted
with CH2Cl2 (3ϫ 5 mL). The combined organic layers were dried
with anhydrous MgSO4, filtered and concentrated under reduced
pressure. The resulting residue was subjected to column chromatog-
raphy on silica gel (PE/Et2O, 99:1 to 70:30) to give the expected
C15 hydroxy compound (139 mg, 80%) as a colorless liquid. [α]2D0
1
= –25.0 (c = 1.0, CHCl3). H NMR (400 MHz, C6D6): δ = 7.89–
7.80 (m, 4 H, Har), 7.27–7.24 (m, 6 H, Har), 5.98–5.85 (m, 1 H, (1S,7S,9S,11R,13R,E)-7-{(R,Z)-3-[(tert-Butyldiphenylsilyloxy)meth-
CH2CH), 5.83–5.76 (m, 1 H, CHCH), 5.21 (t, J = 10.5 Hz, 1 H, yl]pent-1-enyl}-9,11-dimethyl-1,3-dioxan-12,12-dimethyl-6,17-di-
CHCH), 5.09–5.02 (m, 2 H, CH2CH), 4.80–4.74 (m, 1 H, CHOH), oxabicyclo[11.3.1]heptadec-3-en-5-one (27): Acrylate 26 (31 mg,
4.24 [dd, J = 6.4, J = 10.3 Hz, 1 H, C(Me)2CH–O–acetonide], 4.08–
3 . 9 9 (m , 1 H, CH– O – a ce t o ni d e) , 3 . 6 6 –3 . 5 4 ( m , 2 H ,
CH2OTBDPS), 3.42 [dd, J = 1.2, J = 10.8 Hz, 1 H, C(Me)2CH–
O], 3.25–3.18 (m, 2 H, OH and CH2CHCH2CH–O), 2.80–2.72 (m,
0.043 mmol, 1 equiv.) was dissolved in degassed CH2Cl2 (35 mL).
Grubbs II catalyst (10 mg) was quickly added and argon was
bubbled through the solution for 10 min before heating to reflux.
After 2 h, the temperature was lowered to room temperature and
1 H, CHEt), 2.36–2.24 (m, 1 H, CH2CHCH2), 2.20–2.11 (m, 1 H, air was bubbled through the solution to destroy excess catalyst. The
CH2CHCH2), 2.07–1.97 [m, 1 H, CH(OH)CH2], 1.78–1.61 [m, 3 solvent was evaporated and the resulting residue was subjected to
Eur. J. Org. Chem. 2013, 2303–2315
© 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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