80 bar and 100 °C for 20 h. Workup as described above resulted
in 4a (310.0 mg, 2.5 mmol) in 50% yield as a near-colourless oil.
All spectra matched those present in the literature.14 1H-NMR
(400 MHz, CDCl3) d 1.08 (s, 6H, 2 × CH3); 1.80 (t, J = 6.1 Hz,
2H, CH2); 2.35 (ddt, J = 2.0, 4.0, 6.1 Hz, 2H, CH2); 5.88 (dt,
J = 2.0, 10.0 Hz, 1H, RHCCHR); 6.84 (dt, 4.0, 10.0 Hz, 1H,
RHCCHR). 13C-NMR (100 MHz, CDCl3) d 23.2, 24.0, 36.1,
41.3, 128.2, 148.6, 204.5. FTIR (CDCl3): 3033, 2964, 2925, 2870,
1682, 1450, 1131. GC-MS (EI, 70 eV): m/z (%) = 125 (M+ + 1,
45); 108 (3); 95 (5); 68 (100); 53 (5).
tert-Butyl-(1-ethylidene-2,2-dimethyl–but-3-enyloxy)-
dimethylsilane 7
To a stirred prepared solution of LDA (8.0 mmol) under argon
in THF at −78 °C was added 4,4-dimethyl-hex-5-en-3-one (6)
(500.0 mg, 4.0 mmol) in 1 mL THF. This solution was stirred
for 30 min before HMPA (2 mL) and TBSCl (4.1 mmol) were
added. After 10 min the cooling bath was removed and the re-
action was allowed to warm with stirring to RT. After stirring
an additional 2 h, the solvent was removed and the residue
was filtered through a small plug of neutral alumina with n-
hexane to give 7 as a transparent light yellow oil in 38% yield
5-Hydroxy-2,2-dimethyl-cyclohexanone 4c
1
(376 mg, 1.5 mmol). H-NMR (400 MHz, CDCl3) d −0.15 (s,
6H, 2 × CH3); 0.96 (s, 9H, t-Bu); 1.14 (s, 6H, 2 × CH3); 1.52 (d,
J = 8 Hz, 3H, CH3); 4.60 (q, J = 8 Hz, 1H, R2CCHCH3); 4.95
(dd, J = 20, 24 Hz, 2H, RHCCH2); 5.89 (dd, J = 12, 20 Hz,
1H, RHCCH2). 13C-NMR (100 MHz, CDCl3) d −2.81, 11.76,
19.11, 26.08, 26.44, 42.89, 98.94, 111.00, 146.88, 156.73. FTIR
(neat): 2960, 2930, 2858, 1662, 1472, 1320, 1076, 837. HR-EIMS
anal. calc. for C14H28OSi [M]+: 240.1909; anal. found: 240.1900.
Obtained from 4 (200 mg, 1.8 mmol) using method C with
4.0 mg [Rh(cod)Cl]2, 0.26 mL (1.9 mmol) Et3N and 1.89 mL
(1.9 mmol) (cy-hex)2BCl solution in CH2Cl2 at 60 bar and
90 °C for 16 h. Workup as described above resulted in 4b
(148 mg, 1.04 mmol) in 58% yield as a pale-yellow oil. 1H-NMR
(500 MHz, CDCl3) d 1.24 (s, 3H, CH3); 1.56 (s, 3H, CH3); 1.69
(m, 4H, 2 × CH2); 2.10 (d, J = 5 Hz, 2H, a-CH2); 3.58 (m, 1H,
R2CH(OH)). 13C-NMR (125 MHz, CDCl3) d 24.0, 24.1, 25.3,
26.5, 36.6, 47.2, 70.2, 214.4. FTIR (CDCl3): 3466 (broad), 2933,
1702, 1451, 1097, 909. Anal. calc. for C8H14O2: C, 67.6; H, 9.9;
anal. found: C, 67.8; H, 10.1.
5-(tert-Butyl–dimethyl–silanyloxy)-2,2,6-trimethyl-
cyclohexanone 7a
Obtained from tert-butyl-(1-ethylidene-2,2-dimethyl-but-3-
enyloxy)-dimethylsilane (7) (100.0 mg, 0.4 mmol) and method B
using 3 mg Rh(CO)2acac, 40 bar CO/H2 and 80 °C for 24 h in
59% yield (66.0 mg, 0.2 mmol) as a 4:1 mixture of diastereo-
isomers.
4,4-Dimethyl-hex-5-en-3-one 6
A two-necked 250 mL round-bottom flask containing a stirring
mixture of 40 mL sat. aq. NH4Cl solution and 8 mL of THF
was maintained at RT using a water bath as prenyl bromide
(5.8 g, 38.9 mmol) and propionaldehyde (3.0 mL, 52.0 mmol)
were added to the mixture. With continued vigorous stirring,
Zn powder (4.0 g, 62.0 mmol) was slowly added portion-wise
to the mixture. The mixture heated up considerably upon
addition of the metal, and after addition was complete the
reaction was stirred for an additional 2 h, upon which the mix-
ture was extracted with ether, dried and concentrated to give
the crude 4,4-dimethyl-hex-5-en-3-ol, which was taken up in
ether and stirred at RT as 30 mL of Jones reagent was dropped
to the mixture over 30 min. After addition, the mixture was
stirred for an additional 2 h before being extracted with ether
and washed repeatedly with sat. aq. NaHCO3 solution. The
organic layer was separated, dried and concentrated to give
3.5 g (28 mmol) 4,4-dimethyl-hex-5-en-3-one (6) in 72% yield
as a pale yellow oil which was used in future reactions without
further purification. All spectra matched those reported in the
literature.9
cis-Diastereoisomer.
1H-NMR (500 MHz, CDCl3) d 0.05 (s, 6H, 2 × CH3); 0.89 (s,
9H, t-Bu); 1.05 (d, J = 4 Hz, 3H, CH3); 1.13 (s, 3H, CH3); 1.18
(s, 3H, CH3); 1.74–1.81 (m, 2H, CH2); 1.98–2.08 (m, 2H, CH2);
2.78 (dq, J = 3, 5 Hz, 1H, a-CH); 3.45 (dt, J = 3, 7 Hz, 1H,
R2CH(OTBS)). 13C-NMR (125 MHz, CDCl3) d 0.9, 11.3, 16.4,
23.0, 24.3, 25.3, 25.8, 26.5, 27.3, 27.6, 27.7, 32.1, 51.2, 81.4,
212.7. FTIR (CDCl3 film): 2977, 2932, 2872, 1712, 1383, 1111,
909, 734. HR-EIMS anal. calc. for C15H30O2Si: 270.2015; anal.
found: 270.2020.
Acknowledgements
We thank Bayer AG, Leverkusen and Degussa AG, Düsseldorf
for the donation of chemicals, and M.D.K and K.K. thank
the Deutsche Forschungsgemeinschaft (DFG) for financial
support.
References
2,2,6-Trimethylcyclohexanone 6a
1 K. R. Hornberger, C. L. Hamblett and J. L. Leighton, J. Am.
Chem. Soc., 2000, 122, 12894; S. D. Dreher and J. L. Leighton, J.
Am. Chem. Soc., 2001, 123, 341; R. W. Hoffmann and D. Brükner,
New J. Chem., 2001, 25, 369; P. Sun, C. Sun and S. M. Weinreb, J.
Org. Chem., 2003, 67, 4337; S. K. Zahn and B. Breit, J. Org. Chem.,
2001, 66, 4870; P. Liu and E. N. Jacobsen, J. Am. Chem. Soc., 2001,
123, 10772; B. Schmidt, B. Costisella, R. Roggenbuck, M. Westhus,
H. Wildemann and P. Eilbracht, J. Org. Chem., 2001, 66, 7658;
R. Roggenbuck, A. Schmidt and P. Eilbracht, Org. Lett., 2002, 4,
289; I. Ojima, A. C. Moralee and V. C. Vassar, Top. Catal., 2002,
19, 89; E. Teoh, E. M. Campi, W. R. Jackson and A. J. Robinson,
New J. Chem., 2003, 27, 387.
2 Tandem C–C bond formation/hydroformylation: L. Bärfacker,
C. Buss, C. Hollmann, B. E. Kitsos-Rzychon, C. L. Kranemann,
T. Rische, R. Roggenbuck, A. Schmidt and P. Eilbracht, Chem. Rev.,
1999, 99, 3329; M. J. Zacuto, S. J. O’Malley and J. L. Leighton, J.
Am. Chem. Soc., 2002, 124, 7894; B. Breit, Acc. Chem. Res., 2003,
36, 264; P. Köhling, A. M. Schmidt and P. Eilbracht, Org. Lett.,
2003, 5, 3213.
Obtained from 4,4-dimethyl-hex-5-en-3-one (6) (630.0 mg,
5.0 mmol) and method A using 12 mg (0.5 mol%) [Rh(cod)Cl]2
and 95.0 mg (10 mol%) p-TsOH affording 6a in 89%
(620.0 mg, 4.5 mmol) after column chromatography (20:1
n-hexane–MTBE). All spectra matched those reported in the
literature.17
5-Hydroxy-2,2,6-trimethyl-cyclohexanone 6b
Obtained from 4,4-dimethyl-hex-5-en-3-one (6) (202.0 mg,
1.6 mmol) using method C with 4 mg [Rh(cod)Cl]2, 0.23 mL
(1.7 mmol) Et3N and 1.7 mL (1.7 mmol) (cy-hex)2BCl solution
in CH2Cl2 at 60 bar and 90 °C for 16 h. Workup as described
above resulted in 86% yield of 6b (215.0 mg, 1.37 mmol) in up
1
to 20:1 dr as a pale yellow oil. H-NMR (500 MHz, CDCl3) d
1.07 (d, J = 8 Hz, 3H, CH3); 1.18–1.27 (m, 6H, 2 × CH3); 1.53
(m, 2H, CH2); 1.85 (m, 2H, CH2); 2.45 (dq, J = 3.5, 8 Hz, 1H,
a-CH); 3.57 (m, 1H, R2CH(OH)). 13C-NMR (125 MHz, CDCl3)
d 8.0, 24.0, 24.2, 24.4, 29.9, 43.7, 46.0, 70.3, 216.7. FTIR (neat):
3399 (broad), 2934, 1704, 1452, 1100, 972. ESI-MS [M + H]+:
157.1. HR-FABMS anal. calc. for C9H16O2 [M]+: 156.1150;
anal. found: 157.1220.
3 R. L. Funk, J. F. Fitzgerald, T. A. Olmstead, K. S. Para and J. A.
Wos, J. Am. Chem. Soc., 1993, 115, 8849.
4 C. Hollmann and P. Eilbracht, Tetrahedron Lett., 1999, 40, 4313;
C. Hollmann and P. Eilbracht, Tetrahedron, 2000, 56, 1685.
5 M. D. Keränen and P. Eilbracht, Org. Biomol. Chem., 2004, 2, 1688.
6 Y. Hiyashi, S. Orikasa, K. Tanaka, K. Kanoch and Y. Kiso, J. Org.
Chem., 2000, 65, 8402.
O r g . B i o m o l . C h e m . , 2 0 0 4 , 2 , 3 3 7 9 – 3 3 8 4
3 3 8 3