V. Gembus et al.
Bull. Chem. Soc. Jpn. Vol. 82, No. 7 (2009)
839
preceding 1l/1m mixture (235.7 mg, 0.77 mmol) was diluted
with CH2Cl2 (1.5 mL). With cooling (ice bath), Ac2O (0.78 mL,
8.2 mmol) and pyridine (1.5 mL) were added sequentially and the
resulting mixture was stirred overnight at rt before being poured
into a mixture of ether (10 mL) and 1 M HCl (5 mL). The aqueous
layer was extracted with ether (4 © 5 mL) and the pooled organic
phases were washed with 1 M HCl (2 © 7 mL), brine (2 © 10 mL),
and dried (MgSO4). The solvents were evaporated in vacuo and
the residual oil was filtered on a short column of silica gel
(EtOAc:hexane = 95:5) to give, after evaporation of the solvents,
a mixture of the diacetates 1nOAc and 1oOAc as a viscous
colorless oil (281 mg, 93%). TLC (hexane:EtOAc = 3:1) Rf =
0.52; IR (neat, cm¹1): 2933, 1760, 1731, 1652, 1455, 1372, 1205,
1047, 901; 1H NMR (CDCl3): ¤ 1.23 (s, 3H, CCH3), 1.53-1.88
(m, 8.8H), 1.98/2.02/2.09 (3 s, 9H, CH3Carom), 2.04 (s, 3H,
CH3CO), 2.32/2.33 (2 s, 3H, CH3CO), 2.60 (t, J = 6.5 Hz, 2H,
CH2Carom), 4.90/4.95/5.00/5.04 (4 s, 2H, CH2=C), 5.13-5.22
(m, 1.2H, CHOAc/CH2OAc); 13C NMR (CDCl3): ¤ 11.8/12.0/
12.9 (CH3Carom), 18.0/20.5/21.1 (CH3), 20.5 (CH2), 22.6 (CH3),
26.4/29.0/31.2/33.4/41.3 (CH2), 66.8 (CH2OAc), 74.4 (C-O),
77.3 (CHOAc), 112.9/113.0 (CH2=C), 117.1/123.0/124.9/126.7/
126.8/140.7 (Carom), 142.8 (CH2=C), 149.1 (Carom), 169.6/170.3
(C=O); MS (CI-NH3) m/z 407 (M + NH4+), 389 (M + H+), 346
(M ¹ Ac), 329, 286, 247, 203, 165, 121.
2-(3-Pivalyloxy-4-methylpent-4-enyl)-2,5,7,8-tetramethylchro-
man-6-yl Pivalate (1pOPiv) and 2-[4-(Pivalyloxymethyl)pent-4-
enyl]-2,5,7,8-tetramethylchroman-6-yl Pivalate (1qOPiv). Pyr-
idine (1.75 mL) and pivaloyl chloride (0.61 mL, 5 mmol) were
added sequentially to a cooled (ice bath) solution of the preceding
1l/1m mixture (506 mg, 1.66 mmol) in CH2Cl2 (5 mL). After 24 h
stirring at rt, the reaction mixture was diluted with ether (10 mL)
and washed with 1 M HCl (5 mL). The aqueous layer was extracted
with ether (4 © 5 mL) and the pooled organic extracts were washed
with 1 M HCl (2 © 7 mL), brine (2 © 10 mL), and dried (MgSO4).
The residue left by evaporation of the solvents was filtered on a
short column of silica gel (hexane:EtOAc = 9:1) to give, after
evaporation of the solvents, a mixture of the dipivalates 1pOPiv
and 1qOPiv as a colorless viscous oil (752 mg, 96%). TLC
(hexane:EtOAc = 3:1) Rf = 0.68; IR (neat, cm¹1): 2932, 1755,
1576, 1455, 1368, 1210, 1080, 917, 737; 1H NMR (CDCl3): ¤ 1.23
(s, 3H, CCH3), 1.27/1.40 (2 s, 18H, CH3Piv), 1.53-1.88 (m, 6H, 3
CH2), 1.71 (s, 3H, CH3C=), 1.94/1.97/2.07 (3 s, 9H, CH3Carom),
2.60 (t, J = 6.4 Hz, 2H, CH2Carom), 4.87/4.94 (2 s, 2H, CH2=),
5.08-5.15 (m, 1H, CHOPiv); 13C NMR (CDCl3): ¤ 11.8/11.9/12.7
(CH3Carom), 18.2 (CH3C=), 20.5 (CH2Carom), 23.9 (CCH3), 27.1/
27.7 (CH3Piv), 26.6/31.0/31.4/39.2 (4 CH2), 34.7/35.8 (CPiv),
74.3 (CCH3), 76.7/76.8 (CHOPiv), 112.4 (CH2=C), 117.1/122.9/
124.9/126.8/140.6 (Carom), 143.2 (C=CH2), 148.9 (Carom), 177.5/
177.6 (C=O); MS (CI-NH3) m/z 473 (M + H+), 472 (M), 388,
371, 289, 249, 205, 165, 121.
TLC (hexane:ether = 3:1) Rf = 0.27; 1H NMR (CDCl3): ¤ 0.88
(d, J = 6.3 Hz, 6H, 2 CH3CH), 1.14 (s, 3H, CH3COH), 1.18-1.50
(m, 14H, 6 CH2, 2 CH), 1.60/1.68 (2 s, 12H, 4 CH3C=), 1.88-2.06
(m, 4H, 2 CH2CH=), 5.09 (m, 2H, 2 CH=C); 13C NMR (CDCl3):
¤ 17.6/19.6/25.7 (6 CH3), 27.0/27.1 (CH3COH), 25.5/30.8 (4
CH2), 32.9 (2 CH), 37.0/37.1/39.0/39.1 (4 CH2), 72.9 (COH),
124.9 (2 CH=C), 131.1 (2 C=CH);
2-(3-Hydroxy-4-methylpent-4-enyl)-2,5,7,8-tetramethylchro-
man-6-yl Acetate (1lOAc): TLC (hexane:ether = 3:1) Rf = 0.05;
1H NMR (CDCl3): ¤ 1.23 (s, 3H), 1.50-1.88 (m, 6H), 1.71 (2 s,
3H), 1.98/2.02/2.09 (3 s, 9H), 2.33 (s, 3H), 2.61 (t, J = 6.6 Hz,
2H), 4.03-4.08 (m, 1H), 4.31 (s, 1H, OH), 4.84/4.94 (2 m, 2H);
13C NMR (CDCl3): ¤ 11.8/12.0/12.9 (CH3), 17.4/17.5 (CH3), 20.5
(CH3), 20.6 (CH2), 24.2 (CH3), 28.4/28.5 (CH2), 31.5/31.6 (CH2),
35.6/35.8 (CH2), 74.3 (C), 77.3 (CH-O), 111.2/111.4 (C=CH2),
117.1/117.2 (Carom), 123.0 (Carom), 124.9 (Carom), 126.7/126.8
(Carom), 140.7 (Carom), 147.2/147.5 (C), 149.1 (Carom), 169.6/170.3
(C).
6-Chloro-3,7-dimethylocta-1,7-dien-3-ol (3c). Linalool 3b
(500 mg, 3.24 mmol) was chlorinated with Ca(OCl)2 (363.6 mg,
1.65 mmol) as described above for the 1bOAc/1cOAc chlorina-
tion.21 The oily residue left by evaporation of the solvents was
chromatographed on silica gel (hexane/ether) to give 3c as a
yellow oil (360.4 mg, 59%). TLC (hexane:ether = 2:1) Rf = 0.66;
IR (neat, cm¹1): 3419, 2970, 1645, 1452, 1375, 1113, 996, 920;
1H NMR (CDCl3) ¤ 1.28/1.29 (2 s, 3H, CH3COH), 1.40-1.96 (m,
4H, CH2), 1.78 (s, 3H, CH3C=CH2), 4.35 (t, J = 7.3 Hz, 1H,
CHCl), 4.91 (m, 2H, CH2=C), 5.07 (dd, J = 10.7, 1.2 Hz, 1H,
CHH=CH), 5.21 (dd, J = 17.3, 1.2 Hz, 1H, CHH=CH), 5.87 (dd,
J = 17.3, 10.7 Hz, 1H, CH2=CH); 13C NMR (CDCl3): ¤ 16.9/17.0
(CH3C=CH2), 28.0/28.2 (CH3COH), 31.0/31.1 (CH2), 39.1/39.2
(CH2), 67.0/67.1 (CHCl), 72.7/72.8 (COH), 112.1/112.2 (CH2=
CH), 114.1/114.2 (CH2=C), 144.0/144.3 (C=CH2), 144.5/144.6
(CH=CH2); MS (CI-NH3) m/z 137 (M ¹ Cl), 130, 107, 90, 70, 61.
3,7,11,15-Tetramethylhexadeca-1,6,14-trien-3-ol
(3d).
Chlorolinalool 3c (943 mg, 5 mmol) was reacted with 12a
(11 mmol) in THF with added CuI (0.25 mmol) as described
above. The product isolated after hydrolysis was purified by
column chromatography (hexane/ether) to give, successively, the
dehydroisophytol 3d as a colorless oil (310 mg, 21%), and
unreacted 3c (530 mg, 56%). TLC (hexane:ether = 3:1) Rf = 0.29;
IR (neat, cm¹1): 3401, 2970, 1644, 1452, 1376, 1113, 995, 920;
1H NMR (CDCl3): ¤ 0.85/0.87 (2 d, J = 6.4 Hz, 3H, CH3CH),
1.06-1.48 (m, 9H, 4 CH2/CHCH3), 1.28 (s, 3H, CH3COH), 1.58/
1.66 (2 s, 3H, CH3C=), 1.60/1.68 (2 s, 6H, 2 CH3C=), 1.88-2.08
(m, 6H, 3 CH2), 5.12 (m, 2H, 2 C=CH), 5.06 (2 d, J = 10.8 Hz,
1H, CHH=CH), 5.22 (2 d, J = 17.6 Hz, 1H, CHH=CH), 5.86-
5.98 (2 dd, J = 17.5, 10.8 Hz, 1H, CH=CH2); 13C NMR (CDCl3):
¤ 15.9/17.6/19.5/25.5 (CH3), 22.5/22.7 (CH2), 27.4 (CH3COH),
25.3/25.4 (2 CH2), 32.3 (CHCH3), 36.5/36.8/36.9/37.1/39.9/
42.1/42.3 (4 CH2), 73.5 (COH), 111.6/111.7 (CH2=CH), 123.9/
124.6/125.0/125.1 (2 C=CH), 130.9 (C=CH), 136.0/136.1
(C=CH), 145.0 (CH=CH2); MS (CI-NH3) m/z 293 (M + H+),
275 (M ¹ OH), 177, 163, 149, 135, 121, 109, 93, 80, 69, 55.
(E,Z)-2,5,7,8-Tetramethyl-2-(4,8,12-trimethyltrideca-3,11-di-
General Protocol for Catalyst Screening Experiments
(Table 2). The diester (1 mmol) diluted with THF (or ether)
(1.4 mL) was added to the catalyst (0.05 mmol). The resulting
mixture was thoroughly degassed, then cooled to ¹5 °C (ice/
methanol bath) before adding a solution of 12a (1 mmol) in THF
(or ether) with a syringe. The reaction was monitored by TLC
(hexane:ether = 3:1). After 1 h stirring, an excess of 12a was
added portionwise (0.5 mmol each). In each case the reaction
mixture was processed as described above for the Wurtz-coupling
experiment with 1fOAc/1gOAc and the residue left by evaporation
of the solvents was chromatographed on silica gel (hexane/ether);
enyl)chroman-6-ol (1h).
A mixture of TMHQ 2 (50 mg,
0.33 mmol) and CSA (8 mg, 0.03 mmol) was diluted with xylene
(0.8 mL) in a flask equipped with a condenser connected to an
argon/vacuum line. The resulting mixture was thoroughly de-
gassed and the flask was immersed in a thermostated bath (165-
180 °C). After 15 min stirring, the dehydroisophytol 3d (144.4 mg,
0.49 mmol) diluted with xylene (0.4 mL) was added with a syringe
2,6,9,12,16-Pentamethylheptadeca-2,15-dien-9-ol
(13):