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OH
–2
d5
d5
d5
d5
THF, 25 ºC
2Li+
ii. Et2CO, –78
iii. H2O
ºC
I-d10
Scheme 4.
10f-d10
60%
15. Representative example: preparation of compound 10a.
To a deeply colored solution of biphenyl (3 mmol) and
lithium powder (Li(s), 12 mmol) in dry THF (10 ml) at
25 ꢁC with vigorous stirring under Ar, propene was
delivered using a balloon (approx. 3 l, 1 atm). Proper
evacuation of Ar is critical for the reaction with gaseous
alkenes in order to not lengthen unnecessarily the reaction
times. After ca. 1 h, the initial greenish-blue color of I
turned brown. The reaction was then cooled down to
ꢀ78 ꢁC. THF was chosen as solvent instead of THP (of
improved stability towards reductive cleavage, see Ref. 2)
to prevent freezing at this point. 3-Pentanone (8, 6 mmol)
was then added. After 15 min the reaction was hydrolyzed
(H2O) and worked up as usual (3 · 20 ml diethyl ether,
Na2SO4, 15 Torr), purifying 10a by flash chromatography
(silica gel, Hx/EtOAc). A 0.5 wt % of hydroquinone was
added for storage (see Ref. 2). 3-[(1RS,6SR)-6-Isopropyl-
3-phenylcyclohexa-2,4-dienyl]pentan-3-ol (10a): Rf = 0036
(9:1 hexane/ethyl acetate); IR (film): m (cmꢀ1) = 3583,
3486, 3032, 2963, 2879, 1599, 1494, 1461, 1447, 1384,
alkenes, in particular before propene an isobutene,
which only very seldom undergo nucleophilic substitu-
tion processes. Mechanistic considerations and further
theoretical studies to shed light onto the principles driv-
ing this reaction will be further explored.
Acknowledgements
This work was generously supported by the Spanish
´
Ministerio de Educacion
y Ciencia (Grant No.
CTQ2004-01261) and the Generalitat Valenciana (Grant
No. GRUPOS03/135 and GV05/52). C.M. thanks the
University of Alicante for financial support. We also
thank MEDALCHEMY S.L. for a gift of chemicals,
especially lithium powder.
1
References and notes
1367, 1123, 948, 917, 771, 750, 697; H NMR (300 MHz,
CDCl3): dH = 0088 (t, 3H, J = 7.6, CH3CH2), 0092 (d, 3H,
J = 6.6, CH3CH), 0093 (d, 3H, J = 6.9, CH3CH), 0095 (t,
3H, J = 7.7, CH3CH2), 1.49 (br s, 1H, OH), 1.51–1.70 (m,
5H, 2 · CH2CH3, CH3CHCH3), 2.42–2.48 (2m, 2 · 1H,
C@CHCHCOH and CH@CHCHiPr), 5.82 (app. d,
J = 6.4 Hz, 1H, C@CHCHCOH), 5.88 (app. dd, J =
10.0 Hz, J = 6.2 Hz, 1H, CH@CHCHiPr), 6.28 (app. d,
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J = 9.8 Hz, 1H, CH@CHCPh), 7.24–7.42 (m, 5H, Ph); 13
C
NMR: dC = 7.6, 7.9 (2 · CH3CH2), 18.45, 19.45 (CH3-
CHCH3), 27.1, 28.0 (2 · CH2CH3), 34.7 (CH3CHCH3),
38.4 (CH@CHCHiPr), 43.1 (C@CHCHCOH), 78.8
(COH), 122.55 (C@CHCHCOH), 124.35 (CCH@
CHCHiPr), 125.5 (2C, PhCo), 127.0 (PhCp), 128.4 (2C,
PhCm), 130.7(CH@CHCHiPr), 136.1 [CH@C(Ph)CH],
140.8 (PhCi); MS: m/z (%): 266 (<1%, M+ꢀ18), 198 (34),
155 (100), 154 (32), 87 (34). HRMS: calcd for C20H28O:
284.2140; found 284.2092.
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