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L. O. Haustedt et al. / Tetrahedron 59 (2003) 6967–6977
Cp–Ha), 0.62–0.58 (m, 1H, Cp–Hb); 13C NMR (100 MHz,
CDCl3): 160.91 (Cq, C-1), 159.57 (Cq, PMB), 150.75 (CH,
C-8), 147.85 (Cq, C-4), 144.21 (CH, C-3), 134.71 (Cq, C-2),
130.40 (Cq, PMB), 129.67 (CH, PMB), 114.71 (CH, PMB),
106.82 (CH, C-7), 92.44 (Cq, C-6), 75.50 (Cq, C-5), 72.80
(CH2, PMB), 69.44 (CH2, C-11), 61.64 (CH2, C-10), 55.58
(OCH3), 20.81 (CH, C-10), 20.44 (CH, C-9), 14.5 (CH3,
C-20), 13.20 (CH2, Cp–CH2); IR (neat, cm21): 2211, 1741,
1721, 1612, 1573, 1541, 1511, 1368, 1333, 1297, 1172,
1143, 1111, 1079, 1024, 977, 950, 925, 818; MS: m/z (%)
381 (Mþ; 4.37); 279 (80.09); 261 (4.38); 239 (2.61); 218
(4.08); 198 (5.90); 167 (72.46); 149 (100); 121 (91.65); 97
(11.90); 84 (11.94); 71 (51.47); HRMS: calcd for
C22H23NO5: 381.1576; found: 381.1575.
MTB ether, dried (Na2SO4) and purified by flash chroma-
tography yielding 16.0 mg (82%) of propargylic alcohol 19
as a colorless oil (2:1 diastereomeric mixture); H NMR
1
(500 MHz, CDCl3, TMS): 7.26–7.36 (m, 5H, OCH2Ph);
4.46–4.52 (m, 2H; OCH2Ph); 4.45 (m, 1H, H-16); 3.81 (dd,
J¼7.0, 3.3 Hz, 1H, H-14); 3.46–3.62 (m, 2H; H-12); 2.22
(br s, 1H; OH); 2.04 (dtddddd, J¼14.4, 7.7, 3.2 Hz, 1H,
H-13a); 1.85 (d, J¼2.2 Hz, 3H, H-19); 1.73 (mdddd, 1H,
H-13b); 1.06 (s, 3H, Me); 0.89 (s, 3H, Me); 0.88 (s, 9H,
TBS); 0.10 (s, 3H, TBS); 0.06 (s, 3H, TBS); 13C NMR
(125 MHz, CDCl3, TMS): 138.34 (Cq, Bn); 128.32 (CH,
Bn); 127.59 (CH, Bn); 127.53 (CH, Bn); 81.35 (Cq, C-17/
C-18); 78.55 (Cq, C-17/C-18); 76.85 (CH, C-14); 72.86
(CH2, OCH2Ph); 68.54 (CH, C-16); 67.62 (CH2, C-12);
42.10 (Cq, C-15); 33.32 (CH2, C-13); 25.99 (CH3, TBS);
21.40 (CH3, Me); 18.38 (CH3, Me0); 18.18 (Cq, TBS); 13.55
(CH3, C-19); 24.23 (CH3, TBS); 24.27 (CH3, TBS); IR
(neat, cm21): 3451, 3030, 2955, 2918, 2883, 2855, 2116,
1674, 1496, 1471, 1386, 1360, 1253, 1205, 1088, 1027,
1003, 938, 880, 834, 773, 733, 696, 666, 609; MS: m/z
(%) 333 (Mþ2tBu; 2.60), 321 (1.97), 280 (2.28), 279
(8.58), 241 (2.87), 240 (4.53), 239 (23.24), 225 (4.05),
187 (4.21), 173 (23.62), 133 (12.45), 131 (32.14), 92
(9.03), 91 (100.00), 75 (14.68), 73 (13.80); HRMS:
calcd for C19H29O3Si1 (Mþ2tBu): 333.1886; found:
333.1886.
4.1.8. Aldehyde 13. To a stirred solution of 64.8 mg of
Sonogashira product 12 (0.17 mmol) in 2 mL of a CH2Cl2/
water mixture (9:1) was added 38.4 mg of DDQ
(0.425 mmol) at rt. The reaction mixture was stirred for
30 min (TLC showed absence of starting material),
quenched with sat. NaHCO3 solution and extracted with
CH2Cl2. After removal of the solvent the residue was used
without further purification for the next step. The crude
product was dissolved in CH2Cl2 (5 mL), 106 mg of Dess–
Martin periodinane (0.25 mmol) and 43 mg of NaHCO3
(0.51 mmol) were added to the solution which was stirred
for about 20–30 min. Extraction and purification (MTBE/
CH 3:1) afforded 31 mg of aldehyde 13 as brownish yellow
liquid (71% over two steps). [a]2D0¼286.88 (c¼0.22,
CHCl3); 1H NMR (400 MHz, CDCl3, TMS): 9.57 (d,
J¼3.8 Hz, 1H, H-11), 8.19 (s, 1H, H-3), 6.37 (dd, J¼15.8,
9.6 Hz 1H, H-8), 5.87 (d, J¼15.8 Hz, 1H, H-7), 4.38 (q,
J¼7.1 Hz, 2H, H-10), 2.34 (m, 1H, H-10), 2.32–2.24 (m,
1H, H-9), 1.64–1.61 (m, 1H, Cp–Ha), 1.56–1.53 (m, 1H,
Cp–Hb), 1.38 (t, J¼7.1 Hz, 3H, H-20); 13C NMR (100 MHz,
CDCl3, TMS): 199.03 (CH, C-11), 160.56 (Cq, C-1), 147.19
(Cq, C-4), 145.94 (CH, C-8), 144.17 (CH, C-3), 134.42
(Cq, C-2), 108.94 (CH, C-7), 90.89 (Cq, C-6), 76.22 (Cq,
C-5), 61.43 (CH2, C-10), 30.74 (CH, C-10), 27.15 (CH,
C-9), 15.87 (CH2, Cp–CH2), 14.25 (CH3, C-20); IR
(neat, cm21): 2924, 2854, 2214, 1721, 1542, 1370, 1296,
1240, 1145, 1110, 1018, 957, 832, 769, 713; MS: m/z
(%) 259 (Mþ; 10.0), 258 (Mþ21;37.1), 230 (37.7), 202
(23.4), 185 (29.2), 157 (47.3), 128 (100.0), 90 (51.4), 77
(54.2); HRMS: calcd for C14H13NO4: 259.0845; found:
259.0820.
4.1.10. Enone 21. 3.68 mL of allylmagnesium bromide
solution (1.0 M in Et2O; 3.68 mmol) was added at 08C to a
solution of 1.0 g of aldehyde 14 (2.63 mmol) in 5.3 mL of
dry THF (0.5 M). After 2 h at 08C the mixture was
hydrolyzed with saturated NH4Cl solution, extracted with
MTB ether, dried (Na2SO4) with and evaporate. The residue
was dissolved in dry CH2Cl2 and transferred to an ice-cold
suspension of 1.45 g of Dess–Martin periodinane
(3.42 mmol) in 6.6 mL of dry CH2Cl2 (0.4 M). After
being stirred for 3 h at rt the mixture was hydrolyzed with
2N NaOH, extracted with MTB ether, dried and evaporated.
The residue was dissolved in 5.3 mL of dry CH2Cl2 (0.5 M)
and 0.43 mL DBU (2.89 mmol) was added at 08C. The
reaction mixture was warmed to rt, stirred for additional
20 h, hydrolyzed with saturated NH4Cl solution, extracted
with MTB ether, dried (Na2SO4) and evaporated to dryness.
Purification by flash chromatography yielded 832 mg (75%)
of enone 21 as colorless oil. [a]2D0¼23.38 (c¼1.08, CHCl3);
1H NMR (400 MHz, CDCl3, TMS): 7.22–7.25 (m, 2H,
PMB); 6.85–6.88 (m, 2H, PMB); 6.89 (dq, J¼15.1, 6.9 Hz,
1H, H-18); 6.53 (dq, J¼15.1, 1.6 Hz, 1H, H-17); 4.39 (m,
2H, OCH2Ar); 4.03 (dd, J¼7.8, 3.0 Hz, 1H, H-14); 3.80 (s,
3H, OMePMB); 3.45 (m, 2H, H-12); 1.85 (dd, J¼7.0, 1.6 Hz,
3H, H-19); 1.74 (dtddddd, J¼14.1, 7.8, 3.1 Hz, 1H, H-13a);
1.58 (mddt, J¼14.1, 7.8, 6.0 Hz, 1H, H-13b); 1.10 (s, 3H,
Me); 1.07 (s, 3H, Me0); 0.87 (s, 9H, TBS); 0.05 (s, 3H,
TBS); 0.02 (s, 3H, TBS); 13C NMR (100 MHz, CDCl3,
TMS): 203.07 (Cq, C-16); 159.07 (Cq, PMB); 142.37 (CH,
C-18); 130.61 (Cq, PMB); 129.12 (CH, PMB); 127.22 (CH,
C-17); 113.69 (CH, PMB); 73.66 (CH, C-14); 72.32 (CH2,
OCH2Ar); 67.18 (CH2, C-12); 55.24 (CH3, OMePMB); 51.84
(Cq, C-15); 34.21 (CH2, C-13); 26.00 (CH3, TBS); 21.78
(CH3, Me); 19.85 (CH3, Me0); 18.29 (Cq, TBS); 18.17 (CH3,
C-19); 24.02 (CH3, TBS); 24.09 (CH3, TBS); IR (neat,
cm21): 2954, 2939, 2855, 1688, 1624, 1586, 1513, 1464,
1442, 1387, 1360, 1301, 1246, 1173, 1093, 1037, 1005, 967,
4.1.9. Propargylic alcohol 19. Preparation of the
Terashima-Reagent: In a flame-dried flask fitted with a
reflux condenser 104 mg of LiAlH4 (2.74 mmol) were
suspended in 3.0 mL of dry Et2O under a positive pressure
of nitrogen. Within 30 min a solution of 490 mg of (2)-N-
methylephedrine (2.74 mmol) in 8.0 mL of dry Et2O was
added dropwise and the resulting mixture was heated to
reflux for 1 h. Subsequently, 0.69 mL of N-ethylaniline
(5.48 mmol) were added dropwise and the mixture was
again heated to reflux for 1 h.
20 mg of alkynone 18 (0.05 mmol) was solved in 0.2 mL of
dry Et2O (0.25 M). At 2788C 0.43 mL of the Terashima
reagent (0.25 M in Et2O; 0.108 mmol) was added dropwise.
After 2 h at 2788C the reaction mixture was hydrolyzed
with saturated NaHCO3 solution (1 h, rt), extracted with