SYNTHESIS
April 1998
519
ing with EtOAc/hexanes (1:9), to produce alcohol 45 as a colorless oil
1H NMR (200 MHz, CDCl3): δ = 7.60–7.23 (m, 5 H), 6.93 (dt, J = 6.5,
15 Hz, 1 H), 5.81 (d, J = 15 Hz, 1 H), 5.08 (dt, J = 3.7, 6.9 Hz, 1 H),
4.79 (q, J = 6.9 Hz, 1H), 3.71 (s, 3 H), 2.39–1.85 (m, 4 H), 1.65–1.45
(m, 2 H), 0.31 (s, 6 H).
(56 mg, 51 %).
1H NMR (200 MHz, CDCl ): δ = 0.40 (s, 6 H), 1.73–2.03 (m, 6 H),
3
2.06 (br d, J = 2.3 Hz, 1 H), 2.67–2.78 (m, 1 H), 4.15–4.20 (m, 1 H),
7.27–7.67 (m, 5 H).
13C NMR (90 MHz, CDCl3): δ = 211.1, 166.9, 149.2, 138.8, 133.7,
129.1, 127.8, 121.0, 83.2, 81.5, 51.4, 31.6, 27.9, 27.2, –2.2.
IR (neat): ν = 2951, 1938, 1725, 1657 cm-1.
13C NMR (50 MHz, CDCl ): δ = –0.7, 22.4, 30.2, 33.0, 39.4, 74.0,
3
86.6, 107.9, 127.9, 129.4, 133.5, 137.1.
IR (neat): ν = 3600–3300, 2950, 2170 cm–1.
EIMS m/z (%) = 244 (M+, 2), 243 (M+-H, 3), 229 (23), 161 (64), 135
(100).
EIMS m/z (%) = 300 (M+, 5.6), 135 (100).
62b: oil.
HRMS m/z calcd. for C15H20OSi 244.1283 (M+), found 244.1282.
Prepared (90 mg, 86%) from aldehyde 24a (78.0 mg, 0.32 mmol) and
phosphonium ylid 61b (232 mg, 0.64 mmol).
Preparation of Acetylene Alcohol 46:
1H NMR (200MHz, CDCl3): δ = 7.59–7.52 (m, 2 H), 7.39–7.23 (m, 3
H), 6.74 (tq, J = 1.4, 7.5 Hz, 1 H), 5.07 (dt, J = 3.7, 6.8 Hz, 1 H), 4.82
(q, J = 6.8 Hz, 1 H), 4.19 (q, J = 7.1 Hz, 2 H), 2.22–2.11 (m, 2 H),
1.27 (t, J = 7.2 Hz, 3 H), 0.33 (s, 6 H).
A solution of aldehyde 24b (149 mg, 0.58 mmol) in anhyd o-dichlo-
robenzene (5 mL) was gently refluxed at 180°C for 16 h. The mixture
was cooled to r.t. and filtered. The flask was washed with benzene (5
mL) and EtOAc (20 mL). The combined filtrates were concentrated
in vacuo to produce the crude hydroxy silyl acetylene.
To a solution of the above silyl acetylene (149 mg, 0.58 mmol) in
THF (5 mL) under Ar at 0°C was added tetrabutylammonium fluoride
(0.90 mL, 0.90 mmol, 1.0 M solution in THF). The solution was
13C NMR (90 MHz, CDCl3): δ = 211.0, 168.2, 141.8, 139.6, 138.5,
133.6, 129.0, 127.7, 83.3, 81.3, 60.3, 28.4, 28.1, 27.4, 14.2, 12.3, –2.3.
IR (neat): ν = 2934, 1938, 1711, 1649 cm–1.
CIMS m/z (%) = 329 (M++H, 72), 251 (38), 135 (100).
HRMS m/z calcd. for C20H28O2Si 328.1858 (M+), found 328.1857.
warmed to r.t. and stirred for 2 h. Sat. aq NaHCO solution (10 mL)
3
was added and the mixture was stirred for 10 min. The mixture was
74a: oil.
extracted with Et2O (3 × 15 mL). The combined organic layers were
Prepared (367 mg, 73%) from aldehyde 34 (400 mg, 1.60 mmol) and
ylid 61a (688 mg, 2.00 mmol).
washed with brine, dried (MgSO ) and concentrated in vacuo. The
4
residue was purified by flash chromatography, eluting with EtOAc/
hexanes (1:9), to produce hydroxy alkyne 46 as a colorless oil (35 mg,
49% from aldehyde 24b).
1H NMR (200 MHz, CDCl3): δ 7.61–7.52 (m, 2 H), 7.43–7.32 (m, 3
H), 6.96 (dt, J = 7.0, 15.8 Hz, 1 H), 5.80 (dt, J = 1.5, 15.9 Hz, 1 H),
5.03–4.98 (m, 1 H), 3.72 (s, 3 H), 2.20-2.05 (m, 2 H), 1.95–1.82 (m,
2 H), 1.62 (d, J = 4.0 Hz, 3 H), 1.61–1.45 (m, 2 H), 0.29 (s, 6 H).
13C NMR (75 MHz, CDCl3): δ = 209.8, 167.1, 149.3, 139.8, 133.6,
129.0, 127.7, 120.9, 91.7, 81.1, 51.3, 32.4, 31.7, 25.9, 18.0, –2.1.
IR (neat): ν = 2951, 1942, 1726, 1657 cm–1.
1H NMR (200 MHz, CDCl ): δ =1.12–1.93 (m, 9 H), 2.13 (d, J = 2.5
3
Hz, 1 H), 2.76–2.84 (m, 1 H), 3.60–3.72 (m, 1 H).
13C NMR (50 MHz, CDCl ): δ = 22.1, 22.6, 28.6, 31.2, 35.6, 69.6,
3
71.7, 84.3.
IR (neat) 3400–3200, 2940, 2100 cm–1.
EIMS m/z (%) = 124 (M+, 4), 107 (5), 57 (100).
CIMS m/z (%) = 315 (M++H, 21), 237 (30), 149 (61), 135 (100).
74b: oil.
Cyclization of Aldehyde 34:
Prepared (179 mg, 67%) from aldehyde 34 (200 mg, 0.78 mmol) and
ylid 61b (362 mg, 1.00 mmol).
A solution of allenylsilane aldehyde 34 (75 mg, 0.29 mmol) in mesi-
tylene (4 mL) was sealed in a tube, heated in a sand bath at 300°C for
14 h and concentrated in vacuo. The crude product was purified by
preparative TLC (eluting with 5% EtOAc/hexanes) to give cyclopen-
tanol derivative 47 (50 mg, 67%) as an oil.
1H NMR (200 MHz, CDCl3): δ = 7.65–7.58 (m, 2 H), 7.48–7.38 (m,
3 H), 7.76 (t, J = 7.5 Hz, 1 H), 5.09–4.99 (m, 1 H), 4.19 (q, J = 7.2 Hz,
2 H), 2.20–2.08 (m, 2 H), 1.97–1.85 (m, 2 H), 1.78 (s, 3 H), 1.62 (d,
J = 3.6 Hz, 3 H), 1.58–1.39 (m, 2 H), 1.26 (t, J = 7.2 Hz, 3 H), 0.30
(s, 6 H).
1H NMR (300 MHz, CDCl3): δ = 7.67–7.60 (m, 2 H), 7.41–7.35 (m,
3 H), 3.71 (q, J = 5.4 Hz, 1 H), 2.16–1.59 (m, 6 H), 1.28 (s, 3 H), 0.45
(s, 6 H).
13C NMR (90 MHz, CDCl3): δ = 209.9, 168.2, 141.9, 138.9, 133.6,
128.9, 127.7, 91.9, 81.0, 60.3, 32.7, 28.3, 26.5, 18.0, 14.3, 12.3, –2.1.
IR (neat): ν = 2934, 1942, 1710, 1649 cm–1.
13C NMR (75 MHz, CDCl3): δ = 137.3, 133.5, 129.4, 127.9, 111.9,
86.2, 80.2, 45.2, 27.4, 31.8, 24.4, 20.4, –0.6.
HRMS m/z calcd. for C21H30O2Si 342.2015 (M+), found 342.1990.
IR (neat): ν = 3472, 2965, 2158, 1249, 1116 cm–1.
EIMS m/z (%) = 258 (M+, 1.8), 243 (15), 161 (18), 135 (100).
HRMS m/z calcd. for C16H22OSi 258.1440 (M+), found 258.1419.
77: oil.
Prepared (460 mg, 40%) from aldehyde 24b (950 mg, 3.70 mmol) and
ylid 61a (1.72 g, 5.00 mmol).
Cyclization of Aldehyde 51:
1H NMR (200 MHz, CDCl3): δ = 7.59–7.52 (m, 2 H), 7.40–7.35 (m,
3 H), 6.96 (dt, J = 6.9, 15.9 Hz, 1 H), 5.81 (d, J = 15.9 Hz, 1 H), 5.09–
5.02 (m, 1 H), 4.79 (q, J = 6.9 Hz, 1 H), 3.71 (s, 3 H), 2.21–2.09 (m,
2 H), 2.03–1.89 (m, 2 H), 1.48–1.28 (m, 4 H), 0.31 (s, 6 H).
A solution of aldehyde 51 (140 mg, 0.51 mmol) in mesitylene (4 mL)
was sealed in a tube and heated at 300°C for 24 h and concentrated in
vacuo. The crude product was purified by preparative TLC (eluting
with 5% EtOAc/hexanes) to give alkynyl cyclohexanol 52 (57 mg,
41%) as an oil.
Typical Wittig Reaction of Aldehydes:
1H NMR (300 MHz, CDCl3): δ = 7.68–7.62 (m, 2 H), 7.41–7.37 (m,
3 H), 3.23–3.11 (m, 1 H), 1.97–1.53 (m, 6 H), 1.39 (s, 3 H), 1.38–1.22
(m, 2 H), 0.42 (s, 6 H).
To a mixture of methyltriphenylphosphonium bromide (64a, 1.70 g,
4.80 mmol) in THF (100 mL) at 0°C was added BuLi (1.92 mL,
2.5 M in hexanes). After 1h, a solution of aldehyde 24a (1.19 g, 4.90
mmol) in THF (5 mL) was slowly added. The mixture was warmed to
r.t. over 24 h and H2O (50 mL) was added. The aqueous layer was ex-
tracted with Et2O (3 × 20 mL) and the combined organic layers were
washed with brine, dried (MgSO4) and concentrated in vacuo. The
crude product was purified by flash chromatography eluting with
30% EtOAc/hexanes to give alkene 65a (850 mg, 72%) as an oil.
1H NMR (200 MHz, CDCl3): δ = 7.75–7.69 (m, 2 H), 7.54–7.47 (m,
3 H), 6.03–5.90 (m, 1 H), 5.24 (dt, J = 2.0, 3.6 Hz, 1 H), 5.21–5.10
(m, 2 H), 5.01 (q, J = 4.0 Hz, 1 H), 2.30–2.12 (m, 4 H), 1.71–1.60 (m,
2 H), 0.56 (s, 6 H).
13C NMR (75 MHz, CDCl3): δ = 137.5, 133.6, 129.3, 127.9, 111.5,
86.9, 76.3, 41.2, 38.3, 32.6, 26.6, 24.8, 22.5, –0.5.
IR (neat): ν = 3455, 2932, 2162, 1448, 1115 cm–1.
EIMS m/z (%) = 272 (M+, 5), 257 (16), 135 (100).
HRMS m/z calcd. for C17H24Si 272.1596 (M+), found 272.1614.
Formation of α,â-Unsaturated Esters, Typical Procedure:
A solution of aldehyde 24a (137 mg, 0.56 mmol) and phosphonium
ylid 61a (386 mg, 1.12 mmol) in CH2Cl2 (10 mL) was refluxed for
17 h and concentrated in vacuo. The crude product was purified by
preparative TLC (eluting with 25% EtOAc/hexanes) to give 60 mg
(58%) of pure oily ester 62a.
13C NMR (90 MHz, CDCl3): δ = 211.2, 138.5, 133.8, 133.6, 129.0,
127.7, 114.5, 83.7, 81.1, 32.2, 28.8, 27.2, –2.2.