242 JOURNAL OF CHEMICAL RESEARCH 2007
O
O
O
I
I
I
I
O
O
23e
23x
WM
WM
+
I
+
+
+
HO
+
OH
HO
HO
OH
17
19
20
Scheme 4
M+– I: 253.14204. C14H21O4 - I requires M, 253.14398); [α]D
21
18
22
=
(23x), 2,3-endo-methyl (23e) and 6,2-hydride (62) shifts.
These pathways for achieving the transformation 17→18 are
summarised in Scheme 3, while the shorter, 4-step pathway is
detailed in Scheme 4.
The shorter pathway (Scheme 4) involves rearrangements
common to norbornane systems, whereas the longer pathway
requires the unusual 6,2-hydride shifts. Moreover, coset
analysis of the analogous C-3 carbocation failed to afford a
feasible rearrangement pathway. Consequently, we tentatively
attribute formation of the 9-iodo diketal 16 to acid-catalysed,
skeletal rearrangement of 8-iodocamphorquinone during the
ketalisation process via the shorter mechanistic sequence
detailed in Scheme 4.
+15.8°(c1.00,CHCl3);δH0.82(3H,s,10-CH3),1.10(3H,d,J=1.1Hz,
9-CH3), 1.56 (2H, m, 5Ha and 6-Ha), 1.78 (1H, m, 6-Hb), 1.98 (1H, d,
J = 4.2 Hz, 4-H), 2.20 (1H, m, 5-Hb), 3.13 (1H, d, J = 9.7 Hz, 8-Ha),
3.92 (8H, m, 2xOCH2CH2O) and 4.33 (1H, dd, J = 9.7 and 1.2 Hz,
8-Hb); δC 9.9, 19.5, 19.8, 20.7, 31.9, 48.5, 51.9, 53.2, 64.2, 64.6, 65.2,
66.1, 113.0 and 113.5; m/z 380 (M+, 9.2%) and 253 (100);
The residual material from flash chromatography was
chromatographed further [HPLC on Partisil 10; elution hexane–
EtOAc (4:1)] to afford four fractions.
(i) (1R,4S,7R)-(+)-9-Iodocamphorquinone bis(ethylene ketal)
16 as white crystals (102 mg, 6%), m.p. 57–60°C; [α]D = + 6.4°
22
(c 1.00, CHCl3); δH 0.83 (3H, s, 10-CH3), 1.34 (3H, s, 8-CH3), 1.46
(2H, m, 5Ha and 6-Ha), 1.83 (1H, m, 6-Hb), 1.87 (1H, d, J = 4.0 Hz,
4-H), 2.06 (1H, m, 5-Hb), 2.96 (1H, d, J = 9.7 Hz, 9-Ha), 3.42 (1H,
dd, J = 9.7 and 1.3 Hz, 9-Hb) and 3.92 (8H, m, 2xOCH2CH2O); δC
10.1, 18.5, 18.8, 20.6, 29.1, 48.5, 52.6, 53.7, 64.4, 64.6, 65.0, 66.0,
113.0 and 115.6; m/z 380 (M+, 17.6%) and 253 (100).
Experimental
NMR spectra were recorded on a Bruker AVANCE 400 MHz
spectrometer at 303 K in CDCl3, and calibrated using solvent signals.
IR spectra were recorded on a Perkin Elmer FT-IR Spectrum 2000
spectrometer. Low-resolution (EI) mass spectra were obtained on a
Finnigan-Mat GCQ mass spectrometer and high-resolution (EI) mass
spectraonaVG70-SEQdouble-focusingmagneticsectorspectrometer
(Department of Chemistry, University of the Witwatersrand). Optical
rotations were measured on a Perkin Elmer 141 polarimeter using
a 1 dm cell, with concentrations cited in g/100 ml. Optically pure
compounds were derived from commercially available, homochiral,
(1R)-(+)-camphor.
(ii) (1R,4S,7S)-(+)-2,2-(Ethylenedioxy)-8-iodocamphorquinone 12
as a yellow oil (19.4 mg, 1.4%), (Found M+– CH2O: 307.02175.
C11H16O2I – CH2O requires M, 307.01951); νmax(thin film)/cm-1 1749
(C=O); [α]D22 = + 137° (c 1.9, CHCl3); δH 0.92 (3H, s, 10-CH3), 1.16
(3H, d, J = 1.0 Hz, 9-CH3), 1.90 (4H, m, 5-CH2 and 6-CH2), 2.23
(1H, d, J = 3.9 Hz, 4-H), 3.07 (1H, d, J = 9.9 Hz, 8-Ha), 3.43 (1H,
dd, J = 9.9 and 1.1 Hz, 8-Hb) and 4.16 (4H, m, OCH2CH2O); δC 9.2,
16.5, 18.2, 20.3, 33.7, 47.8, 50.9, 58.2, 64.7, 66.3, 106.4 and 215.9.
(iii) (1R,4S,7S)-(–)-3,3-(Ethylenedioxy)-8-iodocamphorquinone 13
(trace amount) as a pale yellow oil; νmax (thin film)/cm-1 1757 (C=O);
[α]D22 = –16.0 (c 0.12 CHCl3); δH 1.07 (3H, s, 10-CH3), 1.08 (3H, s,
9-CH3), 1.76–2.06 (5H, series of overlapping multiplets, 4-H, 5-CH2
and 6-CH2), 3.05 (1H, d, J = 10.5 Hz, 8-Ha), 3.25 (1H, d, J = 10.5 Hz,
8-Hb), 4.17 (4H, m, OCH2CH2O); δC 11.4 (C-8), 18.7 (C-10), 19.4
(C-9) 20.0 (C-6), 31.5 (C-5), 45.1 (C-7), 52.7 (C-4), 59.7 (C-1), 64.5
and 66.3 (OCH2CH2O), 106.4 (C-2) and 213.3 (C=O).
(1R,4S,7S)-(–)-8-Iodocamphorquinone 9
A solution of 8-bromocamphorquinone 64 (4.00 g, 16.3 mmol)
and KI (13.5 g) in DMF (50 ml) was stirred under argon at 110°C
overnight. The mixture was then cooled to room temperature, diluted
with water (200 ml) and extracted with diethyl ether (2 × 100 ml).
The organic extracts were combined, washed with water (3 × 100 ml),
dried (anhydrous Na2SO4) and concentrated in vacuo. The
residue was chromatographed [flash chromatography on silica;
elution with hexane–ethyl acetate (3:1)] to afford (1R,4S,7S)-8-
iodocamphorquinone 9, as yellow crystals (1.50 g, 27.3%), m.p.
78–85°C (Found M+: 291.99603. C10H13O2I requires M, 291.99603);
(iv) Camphorquinone bis(ethylene ketal) 14, as colourless crystals
(trace amount), m.p. 59–63°C (lit.6 58–59°C); δH 0.80, 0.87 and 1.18
(9H, 3xs, 8-, 9- and 10-CH3), 1.31–2.00 (4H, series of multiplets,
5- and 6-CH2), 1.68 (1H, d, J = 4.6, 4-H), 3.74–4.00 (8H, m,
2xOCH2CH2O); δC 9.9, 20.7, 21.0, 21.1, 29.3, 44.5, 52.7, 53.3, 64.2,
64.5, 65.0, 65.9, 113.5 and 114.7.
22
[α]D = –76.5° (c 1.1, CHCl3); νmax(thin film)/cm-1 1754 (C=O);
X-ray analysis of (1R,4S,7S)-(+)-8-iodocamphorquinone bis(ethylene
ketal) 10 and (1R,4S,7R)-(+)-9-iodocamphorquinone bis(ethylene
ketal) 16
δH 1.13 (3H, s, 10-CH3), 1.23 (3H, d, J = 1.0 Hz, 9-CH3), 1.66 (1H,
m, 5-Ha), 1.87 (1H, m, 6-Ha), 2.10 (2H, m, 5-Hb and 6-Hb), 2.76 (1H,
dd, J = 11.1 and 1.0 Hz, 8-Ha), 2.89 (1H, d, J = 5.1 Hz, 4-H), 3.14
(1H, d, J = 11.1 Hz, 8-Hb); δC 9.02, 11.9, 16.3, 21.5, 32.7, 46.8, 58.3,
58.6, 201.2 and 203.3 (C=O); m/z 292 (100%).
Crystal data 10: C14H21IO4, Mr
= 380.21, monoclinic, C2,
a = 16.3127(4), b = 7.1753(2), c = 12.5202(4) Å, b = 97.618(1)°,
V = 1452.54(7) Å3, Dx = 1.739 g cm-3, Z = 4, m = 2.212 mm-1, T = 113K.
The final refinement was based on 2643 reflections and 174 variable
parameters and converged at R1 = 0.0204 (2586 reflections with I >
2s(I)), wR2 = 0.0503 and S = 1.112. The final maximum difference
electron density peak (1.27 eÅ-3, not modelled) was attributed to
an alternative, minor site for atom C17, the two disordered
components giving rise to two slightly different ring conformations.
The correct assignment of absolute structure was indicated by the
Flack parameter value of –0.02(2). Full crystallographic details
have been deposited at the Cambridge Crystallographic Data Centre
(CCDC 639803).
Crystal data 16: C14H21IO4, Mr = 380.21, monoclinic, P21,
a = 7.227(1), b = 22.840(5), c = 13.149(3) Å, b = 92.18(3)°,
V = 2168.9(8) Å3, Dx = 1.747 g cm-3, Z = 6, m = 2.223 mm-1,
T = 113K. Final refinement was based on 7847 reflections and 520
variables and converged at R1 = 0.0343 (6459 reflections with I >
2s(I)), wR2 = 0.0566 and S = 0.973. The final difference electron
density was 0.59 eÅ-3. The Flack parameter value –0.04(1) indicated
the correct assignment of absolute structure. Full crystallographic
details have been deposited at the Cambridge Crystallographic Data
Centre (CCDC 639804).
(1R,4S,7S)-(+)-8-Iodocamphorquinone bis(ethylene ketal) 10, (1R,
4S,7R)-(+)-9-iodocamphorquinone bis(ethylene ketal) 16, (1R,4S,
7S)-(–)-2,2-(ethylenedioxy)-8-iodocamphorquinone 12, (1R,4S,7S)-
(+)-3,3-(ethylenedioxy)-8-iodocamphorquinone13andcamphorquin-
one bis(ethylene ketal) 14
A mixture of 8-iodocamphorquinone 9 (1.30 g, 4.44 mmol), ethylene
glycol (13.4 ml), p-toluene-sulfonic acid (1.40 g, 6.83 mmol) and
benzene (42 ml) was boiled under reflux under nitrogen in a flask
fitted with a Dean-Stark trap containing 5Å molecular sieves.
After 5 days, the mixture was cooled to room temperature, diluted
with diethyl ether (100 ml), washed sequentially with brine (100 ml)
and water (3 × 100 ml), and dried (anhydrous Na2SO4). The solvent
was removed in vacuo, and the crude product was chromatographed
[flash chromatography on silica; elution with hexane–ethyl acetate
(3:1)] to afford (1R,4S,7S)-(+)-8-iodocamphorquinone bis(ethylene
ketal) 10 (400 mg, 24%) as white crystals. An analytical sample
was prepared by further chromatography [HPLC on Partsil 10;
elution with hexane–ethyl acetate 4:1] to give (1R,4S,7S)-(+)-8-
iodocamphorquinone bis(ethylene ketal) 10, m.p. 98–104°C (Found
PAPER: 07/4560