Paper
Organic & Biomolecular Chemistry
1
1
0
2
3
2
.40 (s, 1.4H), 1.34 (s, 1.6H), 1.21 (1.6H), 1.15 (1.4H), 0.93 (s, 1.09 (s, 3H), 0.93 (s, 3H), 0.91 (s, 12H), 0.91–0.88 (m, 1H) ppm;
1
3
.6H), 0.91 (s, 1.4H), 0.90 (s, 1.4H), 0.88 (s, 1.6H), 0.87 (m, 9H),
C-NMR (CDCl , 101 MHz): δ 208.4, 206.2, 76.0, 50.3, 44.7,
3
1
3
.02–0.04 (m, 6H) ppm; C-NMR (CDCl
3
, 101 MHz): δ 218.8, 41.0, 38.8, 30.1, 28.9, 26.1 (3C), 25.8, 24.7, 22.6, 20.9, 18.4,
+
18.1, 76.0, 76.0, 75.9, 74.4, 48.0, 47.4, 47.0, 41.7, 40.5, 39.5, 15.0, −4.2, −4.7 ppm; HRMS (ESI) m/z: [M + H] calcd for
9.4, 34.5, 29.2, 28.8, 28.3, 27.8, 27.6, 27.3, 26.1 (3C), 26.1 (3C), C H O Si 351.2714, found 351.2712; [α] −84.7 (c 0.251,
2
4
2
1
39
2
D
3
5.4, 25.3, 22.4, 22.0, 19.9, 19.0, 18.6, 18.3, 18.3, 16.7, −4.2 CHCl ).
(
1
2C), −4.8, −4.8 ppm; IR (thin film): ν 3427, 2927, 2856, 1692,
460, 1253, 1083 cm− ; HRMS (ESI) m/z: [M + Na] calcd for
1
+
4-((1R,3R,6S)-3-((tert-Butyldimethylsilyl)oxy)-6-ethynyl-2,2,6-
trimethylcyclohexyl)butan-2-one (37)
20 3
C H38NaO Si 377.2482, found 377.2488.
To a suspension of KOtBu (467 mg, 4.17 mmol) in THF
(
4aS,6R,8aS)-6-((tert-Butyldimethylsilyl)oxy)-2,5,5,8a-
(
10 mL) at −78 °C was added a solution of dimethyl(diazo-
tetramethyldecahydro-naphthalene-1,2-diol (70)
methyl)phosphonate (781 mg, 5.20 mmol) in THF (10 mL).
NaBH (561 mg, 14.8 mmol) was added portionwise to a solu- The mixture was stirred for 10 min; then a solution of 36
4
tion of 35 (2.63 g, 7.42 mmol) in MeOH (37 mL) at 0 °C. The (1.23 g, 3.47 mmol) in THF (23 mL) was added dropwise. The
slurry was stirred at 0 °C for 30 min. MeOH was removed mixture was stirred at −78 °C for 12 h, then warmed up to rt.
2
under reduced pressure, and the residue was diluted with sat. Water and Et O were added. The aqueous layer was extracted
aq. NaHCO and DCM. The aqueous layer was extracted three three times with Et O. The organic phase was washed with
3
2
times with DCM. The organic phase was washed with brine, brine, dried over Na
dried over Na SO , filtered and concentrated under reduced reduced pressure. The residue was purified by column
pressure to afford 70 (2.56 g, 97%) as an inconsequential chromatography (SiO ; hexane/EtOAc, 20 : 1) to give alkyne 37
2 4
SO , filtered and concentrated under
2
4
2
1
mixture of 3 diastereoisomers, which were not separated (dr = (906 mg, 74%). R
.8 : 2 : 1.4 : 1). R = 0.13 and 0.18 (hexane/EtOAc, 8 : 1); (CDCl , 400 MHz): δ 3.37–3.35 (m, 1H), 2.88–2.79 (m,
H-NMR (CDCl , 400 MHz): δ 3.36–3.34 (m, 1H), 3.18 (d, J = 1H), 2.55–2.47 (m, 1H), 2.21–2.14 (m, 1H), 2.14 (s, 3H), 2.08
f
= 0.32 (hexane/EtOAc, 12 : 1); H-NMR
4
f
3
1
3
3
.0 Hz, 0.45H), 2.93 (d, J = 5.9 Hz, 0.30H), 2.87 (d, J = 5.3 Hz, (s, 1H), 1.83–1.74 (m, 1H), 1.73–1.40 (m, 6H), 1.22 (s, 3H), 0.92
.25H), 2.15 (td, J = 13.0, 3.7 Hz, 0.25H), 2.01–1.75 (m, 3H), (s, 9H), 0.87 (s, 3H), 0.85 (s, 3H), 0.05 (s, 3H), 0.04 (s, 3H) ppm;
0
1
1
1
0
1
3
.73 (dd, J = 12.6, 2.6 Hz, 0.35H), 1.67–1.62 (m, 0.75H),
C-NMR (CDCl3, 101 MHz): δ 209.6, 94.9, 75.9, 67.2,
.57–1.39 (m, 5H), 1.36–1.31 (m, 1H), 1.29–1.25 (m, 1.35H), 47.5, 46.4, 39.8, 35.4, 33.8, 30.1, 29.1, 26.1 (3C), 25.4, 22.3,
.23 (s, 0.9H), 1.21 (s, 1.35H), 1.16 (s, 0.75H), 1.01 (s, 0.9H), 21.7 (2C), 18.4, −4.2, −4.7 ppm; IR (thin film): ν 3257,
.91–0.90 (m, 9H), 0.87 (br s, 1.35H), 0.86 (br s, 0.75H), 0.86 2954, 2885, 2857, 1709, 1471, 1357, 1256, 1075, 1029,
br s, 0.9H), 0.84 (br s, 0.9H), 0.83 (br s, 0.75H), 0.81 (br s, 1007, 833, 778 cm− ; HRMS (ESI) m/z: [M + H] calcd for
1
+
(
1
3
21 39 2
C H O
Si 351.2714, found 351.2712; [α] 2D 3 −29.5 (c 0.520,
1
.35H), 0.05–0.02 (m, 6H) ppm; C-NMR (CDCl
3
, 101 MHz):
δ 87.0, 84.3, 83.6, 76.9, 76.5, 76.5, 74.0, 73.9, 72.7, 46.1, 46.0, CHCl3).
4
3
0.4, 39.6, 39.2, 39.2, 39.1, 39.0, 38.1, 38.1, 38.0, 36.4,
2.0, 31.8, 30.3, 29.6, 29.5, 29.4, 29.3, 28.5, 26.2 (3C), 26.2
2
2
-((1R,3R,6S)-3-((tert-Butyldimethylsilyl)oxy)-6-ethynyl-
,2,6-trimethylcyclohexyl)ethyl acetate (38)
(3C), 26.1 (3C), 25.6, 25.4, 25.4, 22.4, 22.3, 22.2, 22.1, 20.7,
1
−
1
9.6, 18.4, 18.4, 17.9, 17.5, 13.9, 13.8, −4.2, −4.3, −4.3, −4.7, m-CPBA (108 mg, 0.626 mmol) was added to a solution of 37
4.7, −4.7 ppm; IR (thin film): ν 3431, 2931, 2857, 1461, 1386, (209 mg, 0.596 mmol) in DCM (6.0 mL) at 0 °C. The white
363, 1252, 1079, 1014, 934, 833, 771, 670 cm ; HRMS (ESI) slurry was allowed to warm up to rt and stirred for 48 h. The
−
1
+
m/z: [M + Na] calcd for C20
79.2638.
H
40NaO
3
Si 379.2639, found mixture was cooled to 0 °C, diluted with DCM, and sat. aq.
NaHCO and sat. aq. Na were added. The aqueous layer
was extracted three times with DCM. The organic phase was
washed with sat. aq. NaHCO and brine, dried over Na SO , fil-
tered and concentrated under reduced pressure. The residue
3
3
2 2 3
S O
(1S,2S,4R)-4-((tert-Butyldimethylsilyl)oxy)-1,3,3-trimethyl-
3
2
4
2
-(3-oxobutyl)cyclo-hexanecarbaldehyde (36)
Pb(OAc) (2.72 g, 5.83 mmol) was added in one portion to a was purified by column chromatography (SiO ; hexane/EtOAc,
4
2
solution of 70 (1.60 g, 4.49 mmol) in DCM (56 mL). The slurry 20 : 1) to give 38 (120 mg, 55%). R
f
= 0.44 (hexane/EtOAc,
1
was stirred at rt for 40 min, before being filtered through a pad 10 : 1); H-NMR (CDCl
3
, 400 MHz): δ 4.25–4.13 (m, 2H),
of silica gel, washing Et O. The filtrate was washed with 5% 3.38 (br s, 1H), 2.22–2.15 (m, 1H), 2.10 (s, 1H), 2.04 (s, 3H),
2
NaHSO
3
, sat. aq. NaHCO
3
and brine, dried over Na
2
SO
4
,
1.84–1.75 (m, 1H), 1.74–1.63 (m, 1H), 1.52–1.42 (m, 2H),
filtered and concentrated under reduced pressure. The residue 1.22 (s, 3H), 0.92 (s, 9H), 0.90 (s, 3H), 0.84 (s, 3H), 0.05 (s, 3H),
1
3
was purified by column chromatography (SiO ; hexane/EtOAc, 0.04 (s, 3H) ppm; C-NMR (CDCl , 101 MHz): δ 171.2,
2
3
1
0
0 : 1) to give 36 (1.23 g, 77%) as a single diastereoisomer. R
f
=
94.3, 75.7, 67.4, 66.6, 43.0, 39.4, 35.4, 33.6, 29.1, 26.8, 26.1
1
.15 (hexane/EtOAc, 15 : 1); H-NMR (CDCl
3
, 400 MHz): δ 9.28 (3C), 25.4, 22.4, 21.7, 21.2, 18.4, −4.2, −4.7 ppm; IR (thin
(
s, 1H), 3.42 (dd, J = 4.1, 1.9 Hz, 1H), 2.37 (app ddd, J = 17.1, film): ν 3308, 2930, 2858, 1773, 1739, 1462, 1243, 1079,
1.3, 5.7 Hz, 1H), 2.31–2.22 (m, 1H), 2.09 (s, 3H), 1.97 (td, J = 1028, 834, 772 cm− ; HRMS (ESI) m/z: [M + H] calcd for
1
+
1
1
4
3
2.9, 3.8 Hz, 1H), 1.90–1.81 (m, 2H), 1.68 (ddt, J = 15.7, 11.2,
C
21
H
39
O
3
Si 367.2663, found 367.2661; [α]2 −25.1 (c 0.675,
D
.7 Hz, 1H), 1.52 (dq, J = 13.8, 3.8 Hz, 1H), 1.37–1.27 (m, 2H), CHCl3).
Org. Biomol. Chem.
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