cotton wool plug. The solution was then added to a solution
of tetrakis(triphenylphosphine) Pd (0) (13.86 mg, 0.012 mmol)
and bis-diphenylphosphine ethylene (9.5 mg, 0.024 mmol) in dry
degassed THF (2.3 mL) under reflux at a rate of 1.50 mL h-1
via syringe pump. The reaction mixture was maintained under
reflux for further 2 h, after which the reaction was cooled to
room temperature and filtered through a plug of silica and washed
with diethyl ether. Filtrate was concentrated in vacuo leaving a
yellow oil. The oil was purified by flash column chromatog-
raphy on silver nitrate impregnated silica (TLC grade) using
1 : 12 diethyl ether–hexane elution giving nine-membered ring 15
(40 mg, 42%) as a diastereomeric mixture and seven-membered
ring 18 (27 mg, 28%). (2R*, 8S,9R)-2-(tert-Butoxycarbonyl)-8-
(tert-butyl,dimethylsilanyloxy)-5,9 dimethyl-cyclonon-4-enone (15)
(15b = d1, 15a = d2) nmax(film) 2955, 2926, 2857, 1740, 1706, 1624,
1459, 1252, 1144, 1078, 1067, 838 cm-1. dH(400 MHz, CDCl3) 5.37
(1H, t, J = 8.3 Hz, d2), 5.32 (1H, dt, J = 8.3, 1.2 Hz, d1), 4.05 (1H,
dt, J = 8.6, 4.3 Hz, d1), 3.69 (1H, dt, J = 8.6, 3.0 Hz, d1), 3.61 (1H,
dd, J = 9.4, 3.3 Hz, d2), 3.42 (1H, dd, J = 11.2, 2.1 Hz, d1), 2.87
(1H, dq, J = 8.6, 7.1 Hz, d2), 2.82 (1H, dq, J = 8.6, 7.0 Hz, d1), 2.71
(1H, ddd, J = 14.6, 11.2, 8.3 Hz, d1), 2.52 (1H, dd, J = 8.3, 3.3 Hz,
d2), 2.49 (1H, app dd, J = 9.4, 8.3 Hz, d2), 2.47 (1H, ddd, J = 14.6,
8.3, 2.1 Hz, d1), 2.23 (1H, m, d1), 1.98–1.88 (3H, m, d2), 1.78–1.68
(3H, m, d1), 1.68 (3H, d, J = 1.2 Hz, d1), 1.68 (3H, s, d2), 1.58 (1H,
m, d2), 1.43 (9H, s, d1), 1.42 (9H, s, d2), 1.20 (3H, d, J = 7.0 Hz,
d1), 1.10 (3H, d, J = 7.1 Hz, d2), 0.89 (18H, s), 0.08 (3H, s), 0.07
(3H, s), 0.07 (3H, s), 0.06 (3H, s) ppm. dC(100 MHz; CDCl3) 213.3
(s, d2), 212.1 (s, d1), 168.6 (s, d2), 168.5 (s, d1), 141.3 (s, d2), 139.6
(s, d1), 121.0 (d, d1), 120.4 (d, d2), 81.9 (s, d1), 81.1 (s, d2), 73.6 (d,
d2), 71.0 (d, d1), 58.4 (d, d1), 57.7 (d, d2), 53.5 (d, d1), 52.7 (d, d2),
35.1 (t, d1), 34.2 (t, d2), 28.3 (t, d1), 28.0 (s, d1 and d2), 27.4 (t,
d2), 26.6 (t, d1), 25.9 (q), 25.9 (q), 25.8 (t, d2), 23.4 (q, d2), 22.8 (q,
d1), 18.1 (s), 18.0 (s), 16.2 (q, d1), 15.0 (q, d2), -4.2 (q), -4.3 (q),
-4.4 (q), -4.7 (q) ppm. LRMS (ESI+) m/z 341 (M+NH4-Ot-Bu),
397 (M+H)+, 419 (M+Na)+. HRMS (ESI+) m/z found
419.2584 (M+Na)+, C22H40NaO4Si requires 419.2588 (M+Na)+.
(2R,3S,6S,7R)-2-(tert-Butoxycarbonyl)-6-(tert-butyl, dimethylsi-
lanyloxy)-3,7-dimethyl-3-ethenyl-cycloheptanone (18) (minor = d1,
major = d2) nmax (film) 2931, 2857, 1744, 1699, 1639, 1462, 1369,
1129, 1078, 995 cm-1. dH (400 MHz, CDCl3) 6.22 (1H, dd, J = 17.7,
11.0 Hz, d1), 5.85 (1H, dd, J = 17.4, 10.7 Hz, d2), 5.03 (1H, dd, J =
11.0, 1.1 Hz, d1), 5.02 (1H, dd, J = 17.4, 0.6 Hz, d2), 4.99 (1H, dd,
J = 17.7, 1.1 Hz, d1), 4.98 (1H, dd, J = 10.7, 0.6 Hz, d2), 4.04 (1H,
s, d1), 4.01 (1H, s, d2), 3.67 (1H, ddd, J = 8.1, 4.4, 1.9 Hz, d1), 3.52
(1H, dt, J = 8.7, 3.1 Hz, d1), 2.76 (1H, dq, J = 8.7, 7.0 Hz, d2), 2.61
(1H, dq, J = 7.1, 4.4 Hz, d1), 2.09 (1H, ddd, J = 14.3, 11.9, 2.3 Hz,
d2), 1.91 (1H, ddd, J = 14.7, 7.0, 2.1 Hz, d1), 1.78 (1H, m, d2),
1.75 (1H, app ddd, J = 12.2, 3.1, 2.1 Hz, d1), 1.67 (1H, app ddd,
J = 7.0, 3.1, 2.1 Hz, d1), 1.64 (1H, m, d2), 1.49 (1H, ddd, J = 14.7,
12.2, 2.1 Hz, d1), 1.40 (9H, s, d1), 1.39 (9H, s, d2), 1.22 (1H, m,
d2), 1.20 (3H, s, d1), 1.18 (3H, d, J = 7.0 Hz, d2), 1.07 (3H, s, d2),
1.09 (3H, d, J = 7.1 Hz, d1), 0.93 (9H, s), 0.87 (9H, s), 0.08 (3H,
s), 0.07 (3H, s), 0.04 (6H, s) ppm. dC (100 MHz, CDCl3) 208.3 (s,
d1), 207.4 (s, d2), 167.6 (s, d2), 167.6 (s, d1), 146.5 (d, d2), 142.7
(d, d1), 113.5 (t, d1), 112.1 (t, d2), 81.6 (s, d1), 80.9 (s, d2), 75.7 (d,
d1), 73.2 (d, d2), 66.3 (d, d1), 64.6 (d, d2), 56.1 (d, d1), 56.0 (d, d2),
41.0 (s, d1), 40.5 (s, d2), 38.6 (t, d1), 35.1 (t, d2), 34.1 (t, d1), 28.9
(q, d2), 28.0 (t, d2), 28.1 (q, d1), 27.2 (q, d2), 25.9 (q), 25.8 (q),
20.3 (q, d1), 18.1 (s), 17.9 (s), 15.8 (q, d1), 14.5 (q, d2), -4.2 (q),
-4.6 (q), -4.9 (q) ppm. LRMS (ESI+) m/z 341 (M+NH4-Ot-Bu),
397 (M+H)+, 419 (M+Na). HRMS (ESI+) m/z found 397.2759
(M+H)+, C22H41O4Si requires 397.2769 (M+H)+.
(4R,5S)-tert-Butyl-10-hydroxy-5-(tert-butyl,dimethylsilany-
loxy)-4,8-dimethyl-3-oxodec-8-enoate (16). To a solution of 14
(1.10 g, 2.40 mmol, 1 equiv) in MeOH : H2O (30 mL, 4 : 1) at rt was
added potassium carbonate (662 mg, 4.80 mmol, 2.0 equivs). The
reaction was stirred for 1 h at rt before a saturated aqueous NH4Cl
solution (20 mL) was added and the mixture diluted with EtOAc
(100 mL). After separation of the biphasic mixture, the aqueous
phase was extracted with EtOAc (3 ¥ 50 mL), and the combined
organics were washed with a saturated aqueous NH4Cl solution
(10 mL) and brine (10 mL), dried over mgSO4. The extracts were
filtered and concentrated in vacuo to give the crude as a bright
yellow oil. The oil was purified via flash column chromatography
eluting with petrol : EtOAc, 3 : 1 then 2 : 1, to afford alcohol 16
as a colourless oil (790 mg, 79%). [a]2D4 -46.1 (c 0.84, CHCl3).
n
max (NaCl) 3420, 2930, 2857, 1734, 1717, 1645, 1472, 1456, 1318,
1253, 1152, 1027, 836, 775 cm-1. dH (500 MHz, CDCl3) 5.41 (1H,
t, J = 7.0 Hz), 4.08 (2H, m), 3.87 (1H, dd, J = 11.1, 4.7 Hz), 3.52
(1H, d, J = 15.7 Hz), 3.46 (1H, d, J = 15.7 Hz), 2.83 (1H, dq,
J = 7.1, 4.7 Hz), 2.18 (1H, dt, J = 12.4, 5.4 Hz), 1.94 (1H, dt,
J = 12.4, 4.7 Hz), 1.71 (3H, s), 1.60 – 1.50 (1H, m), 1.45 (9H,
s), 1.43 –1.34 (1H, m), 1.09 (3H, d, J = 7.1 Hz), 0.90 (9H, s),
0.07 (6H, s) ppm. dC (125 MHz, CDCl3) 205.8 (s), 166.7 (s), 139.4
(s), 124.5 (d), 81.7 (s), 73.7 (d), 58.8 (t), 51.5 (d), 50.5 (t), 33.0
(t), 28.3 (t), 28.1 (q), 25.8 (s), 23.3 (q), 11.9 (q), -4.4 (q), -4.4 (q),
-4.9 (q) ppm. LRMS (ESI+) m/z 437 (M+Na)+, 432 (M+NH4)+,
415 (M+H)+, 323 (M-TBS). HRMS (ESI+) m/z found 437.2690
(M+Na)+ C22H42NaO5Si requires 437.2694 (M+Na)+.
(2R,8S,9R)-2-(tert-Butoxycarbonyl)-8-(tert-butyl,dimethylsi-
lanyloxy)-5,9-dimethyl-cyclonon-4-enone (15). To a solution of
16 (755 mg, 1.8 mmol) in CH2Cl2 (25 mL) was added triph-
enylphosphine (699 mg, 2.55 mmol) and N-bromosuccinimide
(454 mg, 2.55 mmol) at -30 ◦C and stirred for 1 h. The flask
was covered by aluminium foil. Once the starting material was
consumed (TLC) the solvents were removed in vacuo at room
temperature and crude was triturated using hot petrol. The solvent
was removed in vacuo and the allylic bromide 17 as crude yellow
oil (721 mg) was submitted to the cyclisation reaction.
To the solution of bromide 17 (721 mg) in DMF (15 mL)
in a flask wrapped with aluminium foil at -50 ◦C was added
caesium carbonate (739 mg, 2.2 mmol) and stirred for 16 h from
-50 ◦C to room temperature. The reaction mixture was diluted
with Et2O (100 mL) and washed with water (3 ¥ 15 mL). The
aqueous layer was extracted with Et2O (3 ¥ 50 mL) and combined
organics were washed with brine (50 mL), dried (MgSO4), filtered
and concentrated in vacuo to yield a brown oil. A flash column
chromatography furnished the product 15 as a colourless oil
(381 mg, 64%) The data is identical to that stated previously.
(1S,2R,4S,6R,7R)-4-(tert-Butoxycarbonyl)-2,7-dimethyl-6-
iodo-10-oxa-bicyclo[5.2.1]decan-3-one (19). Acetic acid (1.90 ml)
was added to a flask containing iodine (65 mg, 0.26 mmol) and
silver(I) acetate (43 mg, 0.26 mmol) at room temperature. The
◦
resulting mixture was stirred rapidly at 35 C for 30 min during
which time a white suspension in a dark orange solution had
formed. The dark orange solution was transferred via syringe to a
This journal is
The Royal Society of Chemistry 2011
Org. Biomol. Chem., 2011, 9, 5062–5078 | 5071
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