Pd-Catalyzed Allylic Substitution on N-Acetyl Neuraminic Acid Derivatives
3 H, CH3), 1.17 (s, 3 H, CH3), 0.89 (s, 9 H, 3ϫCH3), 0.11 (s, 3 H,
CH3), 0.06 (s, 3 H, CH3) ppm. 13C NMR (125 MHz, CDCl3, (t, J9Ј-H,9-H
3J8-H,9Ј-H = 6.5 Hz, 1 H, 8-H), 4.08–3.98 (m, 2 H, 7-H, 9-H), 3.83
2
=
3J9Ј-H,8-H = 6.5 Hz, 1 H, 9Ј-H), 2.99 (m, 3 H,
25 °C): δ = 170.5 (CO), 162.6 (CO), 157.1 (Cq-Ph), 144.6 (C-2),
130.0 (Ph), 120.7 (Ph), 114.3 (Ph), 118.3 (Cq-Ph), 108.4 (Cq), 106.7
(C-3), 79.0 (C-6), 76.1 (C-8), 69.3 and 69.0 (C-7, C-4), 64.5 (C-
9), 52.4 (OCH3), 48.7 (C-5), 44.5 [C(CH3)3], 29.7 (CH2NH), 28.4
CO2CH3), 2.03 (s, 3 H, COCH3), 1.34 (s, 6 H, CH3), 0.88 [s, 9 H, SiC-
(CH3)3], 0.20, 0.13 (s, 6 H, SiCH3) ppm. 13C NMR (125 MHz,
CDCl3, 25 °C): δ = 170.5 (COCH3), 165.3 (CO2CH3), 134.7, 134.0,
2
130.8, 130.6, 130.4, 128.6, 128.4, 108.6 [C(CH3)2], 105.9 (d, JP,C-2
2
2
[C(CH3)3], 26.4 (CH3), 26.0 [SiC(CH3)3], 25.0 (CH3), 23.4 = 6 Hz, C-2), 95.4 (d, JP,C-3 = 4 Hz, C-3), 86.0 (d, JP,C-4 = 31 Hz,
(NHCOCH3), 18.4 (SiC), –3.4 (SiCH3), –4.5 (SiCH3) ppm. IR C-4), 81.7 (C-6), 76.2 (C-8), 73.3 (C-7), 66.4 (C-9), 52.2 (CO2CH3),
(neat): ν = 3318, 2952, 2929, 2855, 1713, 1693, 1681, 1659, 1537, 46.7 (d, 3JP,C-5 = 5 Hz, C-5), 26.6 [C(CH3)2], 26.0 [SiC(CH3)3], 25.5
˜
1530, 1366, 1249, 1159, 1127, 1024, 835, 776 cm–1. HRMS (ESI):
calcd. for C33H52N2O10SiNa [M + Na]+ 687.3259; found 687.3289.
[C(CH3)2], 22.9 (COCH3), 18.3 [SiC(CH3)3], –3.6, –4.0 [Si(CH3)2]
ppm. 31P NMR (202 MHz, CDCl3): δ = 22.3 ppm. HRMS (ESI):
calcd. for C39H5137ClNO7P106PdSiNa [M + Na]+ 870.1764; found
870.1747.
Chloro-Bridged Dimer 22: Degassed THF (1.2 mL) was added to a
mixture of 8 (112 mg, 0.199 mmol), LiCl (34 mg, 0.8 mmol), and
Pd(dba)2 (103 mg, 0.179 mmol). After 4 h at room temp., the reac-
tion mixture was concentrated and purified by flash chromatog-
raphy on silica gel (heptane/AcOEt, 7:3 to 0:1) followed by
recrystallization (Et2O/pentane, 1:2) to afford 22 as a yellow solid
(76 mg, 72%). 1H NMR (500 MHz, CDCl3, 25 °C): δ = 6.87 (br. s,
Complex 25: dppb (6.5 mg, 15 µmol) and AgOTf (2.9 mg,
11.3 µmol) were added successively to a solution of 20 (6 mg,
5.1 µmol) in CDCl3 (0.5 mL). After 1 h at room temp., the reaction
1
mixture was filtered through a pad of Celite. H NMR (500 MHz,
3
CDCl3, 25 °C): δ = 7.80–7.15 (m, 20 H, Ph), 7.03 (d, JNH,5-H
=
3
3
3
7.0 Hz, 1 H, NH), 5.74 (d, J3-H,4-H = 7.0 Hz, 1 H, 3-H), 5.05–4.95
1 H, NH), 5.79 (d, J3-H,4-H = 6.5 Hz, 1 H, 3-H), 4.95 (t, J4-H,3-H
3
3J4-H,5-H = 6.5 Hz, 1 H, 4-H), 3.95–3.90 (m, 3 H, 6-H, 7-H, 8-
(m, 1 H, 4-H), 4.30–4.20 (m, 1 H, 5-H), 4.10 (dd, J6-H,7-H = 3.0,
=
3J6-H,5-H = 10.5 Hz, 1 H, 6-H), 3.94 (br. s, 1 H, 7-H), 3.84 (td,
3
3
H), 3.87 (dd, J5-H,4-H = 6.5, J5-H,6-H = 11.0 Hz, 1 H, 5-H), 3.84
3J8-H,7-H = 2.0, J8-H,9-H = J8-H,9Ј-H = 8.0 Hz, 1 H, 8-H), 3.46 (t,
3
3
(t, 2J9-H,9Ј-H = 3J9-H,8-H = 6.5 Hz, 1 H, 9-H), 3.71 (s, 3 H, CO2CH3),
3J9-H,8-H = J9-H,9Ј-H = 8.0 Hz, 1 H, 9Ј-H), 3.38–3.31 (m, 4 H, 9Ј-
2
2
3.58 (t, J9Ј-H,9-H
=
3J9Ј-H,8-H = 6.5 Hz, 1 H, 9Ј-H), 1.97 (s, 3 H,
H, CO2CH3), 3.29–3.20 (m, 1 H, PCH2), 3.17–3.07 (m, 1 H, PCH2),
2.66–2.55 (m, 1 H, PCH2), 2.32–2.22 (m, 1 H, PCH2), 1.98–1.88
(m, 1 H, CH2), 1.75–1.65 (m, 1 H, CH2), 1.53 (s, 3 H, COCH3),
1.45–1.25 (m, 8 H, 2ϫOCH3, 2ϫCH2), 0.76 [s, 9 H, SiC(CH3)3],
0.00, –0.09 (s, 6 H, SiCH3) ppm. 13C NMR (125 MHz, CDCl3,
COCH3), 1.23 (s, 3 H, OCH3), 1.15 (s, 3 H, OCH3), 0.72 [s, 9 H,
SiC(CH3)3], 0.01, –0.0 (s, 6 H, SiCH3) ppm. 13C NMR (125 MHz,
CDCl3, 25 °C): δ = 170.5 (COCH3), 164.1 (CO2CH3), 108.7
[C(CH3)2], 107.7 (C-2), 88.4 (C-3), 82.2 (C-5), 76.2 (C-8), 75.2 (C-
7), 70.3 (C-4), 65.8 (C-9), 53.2 (CO2CH3), 48.9 (C-6), 26.4
[C(CH3)2], 25.9 [SiC(CH3)3], 25.0 [C(CH3)2], 22.6 (COCH3), 18.1
3
25 °C): δ = 171.5 (COCH3), 164.5 (d, JP,C-1 = 5 Hz, CO2CH3),
135.1, 134.8, 134.7, 134.6, 133.8, 133.5, 133.3, 133.2, 133.1, 133.0,
132.8, 132.6, 132.5, 132.4, 132.3, 132.1, 132.0, 131.8, 131.7, 131.6,
131.4, 130.6, 130.9, 130.8, 130.7, 130.4, 130.1, 129.5, 129.4, 129.3,
129.2, 129.1, 129.0, 128.9, 128.8, 128.7, 128.6, 128.5, 127.7, 127.3,
120.4 (m, C-2), 107.3 [C(CH3)2], 94.9 (m, C-3), 78.9 (C-4, C-6),
77.5 (C-8), 69.0 (C-7), 64.3 (C-9), 52.7 (CO2CH3), 45.9 (m, C-5),
[SiC(CH ) ], –3.3, –4.4 [Si(CH ) ] ppm. IR (neat): ν = 2931, 1750,
˜
3 3
3 2
1733, 1664, 1491, 1304, 1256, 1076, 1041, 835, 808 cm–1. MS (ESI):
m/z = 1190.2 (73) [M + Na]+, 1191.2 (100) [M + Na]+, 1192.2
(46) [M + Na]+, 1193.2 (73) [M + Na]+. HRMS (ESI): calcd. for
C42H7235Cl2N2O14106Pd108PdSi2Na 1191.1871; found 1191.1914.
1
Complex 23: A solution of 20 (5.1 mg, 4.4 µmol) and PPh3 (2.3 mg,
8.7 µmol) in CH2Cl2 (0.5 mL) was stirred at room temp. for 1 h;
AgOBz (2 mg, 8.7 µmol) was then added, and, after stirring for
further 1 h, the reaction mixture was filtered through a pad of Ce-
lite and concentrated. 1H NMR (500 MHz, CDCl3, 25 °C): δ = 8.90
26.4 [C(CH3)2], 26.3 (d, JP,C = 24 Hz, PCH2), 26.1 [SiC(CH3)3],
25.5 [C(CH3)2], 25.3 (d, 1JP,C = 22 Hz, PCH2), 23.3 (COCH3), 22.9
2
2
(d, JP,C = 4 Hz, CH2), 22.0 (d, JP,C = 6 Hz, CH2), 18.3 [SiC-
(CH3)3], –3.0, –5.5 [Si(CH3)2] ppm. 31P NMR (202 MHz, CDCl3,
25 °C): δ = 25.5 (d, J = 61.5 Hz), 11.1 (d, J = 61.5 Hz) ppm. MS
3
= 974.3 [M +
H]+. HRMS (ESI): calcd. for
(d, JNH,5-H = 9.0 Hz, 1 H, NH), 7.45–6.92 (m, 20 H, Ph), 5.86 (d,
(ESI): m/z
3
3
3J3-H,4-H = 8.0 Hz, 1 H, 3-H), 5.47 (td, J = 3.0, J4-H,3-H = J4-H,5-
C49H64NO7P2106PdSi 974.2962; found 974.2885.
3
= 8.0 Hz, 1 H, 4-H), 4.30 (d, J = 8.5 Hz, 1 H, 6-H), 4.20–4.12
H
5-Acetamido-2,6-anhydro-3,4,5-trideoxy-4-morpholino-D-glycero-D-
3
3
(m, 1 H, 5-H), 3.90 (q, J8-H,7-H = 3J8-H,9-H = J8-H,9Ј-H = 5.5 Hz, 1
H, 8-H), 3.77–3.72 (m, 2 H, 7-H, 9-H), 3.57–3.50 (m, 1 H, 9Ј-H),
2.67 (m, 3 H, CO2CH3), 1.72 (s, 3 H, COCH3), 1.11 (s, 3 H, OCH3),
1.07 (s, 3 H, OCH3), 0.61 [s, 9 H, SiC(CH3)3], –0.01, –0.15 (s, 6
H, SiCH3) ppm. 13C NMR (125 MHz, CDCl3, 25 °C): δ = 171.0
(COCH3), 166.9 (CO2CH3), 134.0, 133.9, 132.2, 132.1, 132.0, 130.6,
130.0, 129.6, 129.5, 128.6, 128.5, 128.4, 127.5, 108.3 [C(CH3)2], 96.2
(d, J = 5 Hz, C-2), 95.4 (d, J = 4 Hz, C-3), 94.2 (d, J = 27.5 Hz,
C-4), 81.4 (C-6), 76.8 (C-8), 71.5 (C-7), 66.1 (C-9), 52.0 (CO2CH3),
44.6 (d, J = 5 Hz, C-5), 26.6 [C(CH3)2], 26.1 [SiC(CH3)3], 25.6
[C(CH3)2], 25.5 [C(CH3)2], 23.1 (COCH3), 18.4 [SiC(CH3)3], –3.5,
–4.2 [Si(CH3)2] ppm. 31P NMR (202 MHz, CDCl3): δ = 25.9 ppm.
MS (ESI): m/z = 954.2 [M + Na]+. HRMS (ESI): calcd. for
C46H56NO9P106PdSiNa 954.2394; found 954.2384.
galacto-non-2-enoate (40): TBAF (1 in THF, 240 µL) was added
to a solution of 36 (43 mg, 81 µmol) in THF (1 mL), and the mix-
ture was stirred at room temp. for 2 h. After evaporation of the
solvents, the residue was purified by flash column chromatography
on silica gel (EtOAc/EtOH, 98:2 to 95:5) to give the expected com-
pound 35 (30 mg, 90%). This was then diluted with MeOH (2 mL)
and treated with NaOH (1, 200 µL) at room temp. for 24 h. The
mixture was neutralized with Dowex H+ and filtered, and the sol-
vents were removed under reduced pressure. AcOH (80% in water,
0.5 mL) was added to the crude residue, and the mixture was stirred
at room temp. for 3 d. After evaporation of the solvents, the residue
was chromatographed on Sephadex LH20 (MeOH) to give the ex-
pected 40 as a white solid (23 mg, 91%); m.p. 224–226 °C. [α]2D5
+31.5 (c = 1.0 in MeOH). H NMR (500 MHz, D2O, 25 °C): δ =
=
1
3
3
3
Complex 24: A solution of 19 (4.8 mg, 4.1 µmol) and PPh3 (2.2 mg,
5.72 (d, J3-H,4-H = 2.5 Hz, 1 H, 3-H), 4.34 (t, J5-H,6-H = J5-H,4-H
8.2 µmol) in CDCl3 (0.5 mL) was stirred at room temp. for 1 h. 1H = 9.5 Hz, 1 H, 5-H), 4.14 (d, J6-H,5-H = 9.5 Hz, 1 H, 6-H), 3.88
(ddd, J8-H,9-H = 2.5, J8-H,9Ј-H = 6.0, J8-H,7-H = 9.5 Hz,1 H, 8-H),
H, NH), 7.80–7.35 (m, 15 H, Ph), 6.02 (d, J3-H,4-H = 8.0 Hz, 1 H, 3.82 (dd, J9-H,8-H = 2.5, J9-H,9Ј-H = 12.0 Hz, 1 H, 9-H), 3.78–3.68
3
3
3
3
3
NMR (500 MHz, CDCl3, 25 °C): δ = 8.02 (d, JNH,5-H = 8.4 Hz, 1
3
3
2
3
3
3-H), 5.55–5.45 (m, 1 H, 4-H), 4.51–4.38 (m, 1 H, 5-H), 4.31 (d, (m, 4 H, CH2N), 3.64 (dd, J4-H,3-H = 2.5, J4-H,5-H = 9.5 Hz, 1 H,
3
3
2
3J5-H,6-H = 7.0 Hz, 1 H, 6-H), 4.13 (q, J8-H,7-H
=
3J8-H,9-H
=
4-H), 3.59 (dd, J9Ј-H,8-H = 6.0, J9Ј-H,9-H = 12.0 Hz, 1 H, 9Ј-H),
Eur. J. Org. Chem. 2010, 2280–2294
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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