New synthetic route to ketones from camphene and β-pinene

Article abstract of DOI:10.1023/B:CONC.0000018108.77705.0c

Camphene or β-pinene was treated with Cp₂Zr(H)Cl (Cp = h⁵-C₅H₅) in THF to give organozirconium (IV) complexes, which were trapped with acetyl chloride or benzoyl chloride in the presence of CuI to afford ketones

Full text of DOI:10.1023/B:CONC.0000018108.77705.0c

Chemistry of Natural Compounds, Vol. 39, No. 6, 2003
NEW SYNTHETIC ROUTE TO KETONES
FROM CAMPHENE AND
β-PINENE
P. Zhong, J. Ding, and X. Zhang
UDC 547.598.5
Camphene or β-pinene was treated with Cp2Zr(H)Cl (Cp = h5–C5H5) in THF to give organozirconium (IV)
complexes, which were trapped with acetyl chloride or benzoyl chloride in the presence of CuI to afford
ketones in yields of 63% to 74%.
Key words: ketones, regioselectivity, camphene, β-pinene, hydrozirconation, synthesis.
Ketones made from terpene, such as camphene or β-pinene, usually have a pleasant odor [1]. It was reported [2] that
Vismeir-Haack reaction of camphene gave ω-formylcamphene, which treated with Grignard reagents followed by hydrolysis
and oxidation to give ω-acylcamphene compounds [3]. But the yields were not high and the reaction process was complex.
Recently an organometallic reagent was used for the preparation of ketones from terpene. For example, the reaction
of a diorganozinc compound, prepared from β-pinene, with acid chlorides in the presence of CoBr2 [4] or CuCl×2LiCl [5]
afforded (–)-(1S, 2S)-6,6-dimethyl-2-(2-oxo-2-phenylethyl)-bicyclo[3.1.1]heptane. The same ketone was also prepared by
reaction of the appropriate 8-(acyloxy)quinoline with an organoaluminum reagent [6]. But the organozinc reagent and the
organoaluminum reagent are not easily available.
Hydrozirconation has recently been developed as a procedure for functionalizing alkenes and alkynes via
organozirconium (IV) intermediates. These intermediates react with a varietyof electrophilic reagents to give organic products
in high yield [7–9].
Cp Zr(H)Cl
2
RCOCl, CuI
50 C, 5 - 8h
R
THF, rt
°
ZrCp Cl
H
2
H
O
5
3
1
O
ZrCp Cl
2
R
Cp Zr(H)Cl
RCOCl, CuI
50°C, 5 - 8h
2
THF, rt
2
4
6
Now we report a new synthetic route to the ketones from camphene or β-pinene. Camphene (1) or β-pinene (2) was
treated with Cp2Zr(H)Cl (Cp = h5-C5H5) in THF to give organozirconium (IV) complexes 3 or 4, which were trapped
respectively with acetyl chloride or benzoyl chloride in the presence of CuI to afford ketones 5 or 6 (Table 1).
Department ofChemistry, Wenzhou Normal College, Wenzhou 325027, P. R. China, fax (086-577) 88373091, e-mail:
zhongp0512@sina.com.cn. Pablished in Khimiya Prirodnykh Soedinenii, No. 6, pp. 455-456, November-December, 2003.
Original article submitted July 18, 2003.
0009-3130/03/3906-0549$25.00 ©2003 Plenum Publishing Corporation
549

TABLE 1. Synthesis of Ketones 5 and 6
Product
R
Yield*, %
5a
5b
CH3
Ph
63
72
70
68
74
5c
6a
6b
4-ClC6H4
CH3
Ph
______
*Isolated yield based on camphene or β-pinene.
TABLE 2. Synthesis of Ketones 5 and Thioesters 8
Product*
R (Ar)
Temperature, °C
Time, h
Yield,* %
5b
5d
8a
8b
Ph
PhCH2
Ph
40
40
0
8
8
1
1
38
29
54
61
4-MeC6H4
0
______
*Isolated yield based on camphene.
1. Cp Zr(H)Cl
2
ZrCp Cl
2
2. CO
H
O
1
7
RX
PdCl (PPh )
ArSCl
2
3 2
S
R
Ar
H
H
O
O
5
8
5b: R = C H , 5d: R = C H CH ;
6
5
6
5
2
8a: R = C H S, 8b: R = 4-MeC H S
6
5
6 4
All the compounds 5 and 6 were purified by preparative TLC on silica gel and fully characterized by NMR
spectroscopy. The 1H NMR spectra of 5a [10], 6a [6], and 6b [5] were identical to those reported in the references cited. The
endo configuration was confirmed by 1H NMR.
The method has some attractive advantages such as mild reaction conditions, simple procedure, shorter reaction time,
and high regio- and stereoselectivity.
The ketones 5 and thioesters 8 could also be obtained given as follows. Camphene 1 reacted with Cp2Zr(H)Cl and CO
to give acylzirconocene chloride derivative 7, which was trapped with aryl halides and arylsulfenyl chlorides to afford ketones
5 and thioesters 8 [11] (Table 2).
550

EXPERIMENTAL
1HNMRspectra were recorded on a Brucker AC-300MHz in CDCl3 with TMS as internal standard. Mass spectra were
determined using a Finrigan 8230 mass spectrometer. IR spectra were obtained in neat capillary cells on a Shimadzu IR-408
instrument. Microanalyses were performed using a Yamaco MT-3 CHN micro-elemental analyzer. The reaction were carried
out in pre-dried glassware (150°C, 4 h) and cooled under a stream of dry nitrogen. All solvents were dried, deoxygenated, and
redistilled before use. Analytical data of all compounds corresponded to those calculated.
General Procedure for the Synthesis of 5a–c and 6a–b. A mixture of Cp2Zr(H)Cl [8] (2 mmol) and camphene (1)
or β-pinene (2) (2 mmol) in THF (8 mL) was stirred at room temperature for 40 min. The resulting solution was injected into
a reaction vessel which contained acyl halide (2.5 mmol), CuI (1.0 mmol) and 6 ml THF. The reaction mixture was stirred at
50°C for 8 h. Then it was treated with a saturated aqueous solution of ammonium chloride and extracted with Et O (3 ×10 mL).
2
The residue was purified by preparative TLC on silica gel using hexane as eluent to afford 5 and 6.
General Procedure for the Synthesis of 5b and 5d. A mixture of Cp2Zr(H)Cl [8] (1.5 mmol) and camphene (1)
(3 mmol) in THF (10 mL) was stirred at room temperature for 30 min to yield a clear solution. After the mixture had been
stirred under an atmosphere of CO for 3 h, C6H5I or C6H5CH2Br (1 mmol), PdCl2(PPh3)3 (0.1 mmol) was added at 40°C, and
the mixture was stirred for 8 h. After removal of solvent, the residue was purified by preparative TLC on silica gel eluting with
hexane to afford 5b and 5d.
General Procedure for the Synthesis of 8a–b. A mixture of Cp2Zr(H)Cl [8] (1.5 mmol) and camphene (1) (3 mmol)
in THF (10 mL) was stirred at room temperature for 30 min to yield a clear solution. After the mixture had been stirred under
an atmosphere of CO for 3 h, C6H5SCl or 4-MeC6H4SCl (1 mmol) was added at 0°C, and the mixture was stirred for 1 h. After
removal of solvent, the residue was purified by preparative TLC on silica gel eluting with hexane to afford 8a and 8b.
5a: [10] C12H20O, oil. IR (film, ν, cm-1) 2980, 2920, 2850, 1740, 1440, 1370, 1235, 1040; 1H NMR: 4.05–3.90 (m,
1 H, CHR ), 3.55 (s, 3H, COCH ), 3.50–3.40 (m, 2H, CH CO). 2.00–1.55 (m, 8 H, CH and CH), 1.16 (s, 3H, CH ), 0.95 (s,
2
3
3
2
3
3H, CH3); MS: m/z 165 (M-15, 5.33), 91 (88.60), 43 (100%).
5b: C17H22O, oil. IR (film, ν, cm-1) 3020, 2920, 2850, 1740, 1440, 1370, 1235, 1040; 1HNMR: 8.25–7.90 (m, 2H, Ph),
7.55–7.40 (m, 3H, Ph), 4.35–4.20 (m, 1H, CHR3), 3.60–3.45 (m, 2H, CH2CO), 2.00–1.55 (m, 8H, CH2 and CH), 1.18 (s, 3H,
CH3), 0.90 (s, 3H, CH3); MS: m/z 226 (M-16, 0.40), 122 (53.27), 105 (100), 77 (38.96%).
5c: C17H21ClO, oil. IR (film, ν, cm-1) 3015, 29150, 2855, 1730, 1440, 1375, 1240, 1040; 1H NMR: 8.10, 7.50 (4H, AB-
system, J = 7.4 Hz, Ph), 4.30–4.15 (m, 1H, CHR3), 3.65–3.50 (m, 2H, CH2CO), 2.00–1.50 (m, 8H, CH2 and CH), 1.20 (s, 3H,
CH3), 0.95 (s, 3H, CH3); MS: m/z 260 (M-16, 2.60), 139 (100), 111 (45.32%).
5d: C18H24O, oil. IR (film, ν, cm-1) 3020, 1720, 1508; 1H NMR: 7.30–7.00 (m.5H), 3.95 (s, 2H, CH2Ph), 3.15 (m, 1H),
+
2.15 (m, 2H, CH2CO), 2.00–0.80 (m, 8H), 0.92 (s, 3H), 0.85 (s, 3H); MS: m/z 256 (M , 4.0), 226 (M-30, 100), 165 (M-91, 20),
135 (18), 91 (16%).
6a [6]: C12H20O, oil. IR (film, ν, cm-1) 2940, 2850, 1735, 1440, 1375, 1230, 1100, 1020; 1H NMR: 4.05–3.95 (m, 2
H, CH2CO), 3.30 (s, 3H, COCH3), 2.05–1.35 (m, 9H, CH2 and CH), 1.20 (s, 3H, CH3), 0.84 (s, 3H, CH3); MS: m/z 165 (M-15,
6.14), 91 (100), 43 (96.47%).
6b [5]: C17H22O, oil. IR (film, ν, cm-1) 3030, 2920, 2860, 1785, 1720, 1595, 1455, 1280, 1210, 1100, 1020; 1H NMR:
8.10–7.95 (m, 2H, Ph), 7.50–7.35 (m, 3H, Ph), 4.50–4.35 (m, 2H, CH2CO), 2.50–1.35 (m, 9H CH2 and CH), 1.15 (s, 3H, CH3),
0.65 (s, 3H, CH3); MS: m/z 226 (M-16, 0.77), 122 (37.91), 105 (100), 77 (54.45%).
8a: C17H22OS, oil. IR (film, ν, cm-1) 3020, 1720, 1510; 1H NMR: 7.20–6.80 (m, 5H, Ph), 3.15 (m, 1H,), 2.30 (m, 2H,
+
CH2CO), 2.00–0.85 (m, 8H), 0.93 (s, 3H), 0.86 (s, 3H); MS: m/z 274 (M , 1.5), 244 (M-30, 100), 165 (M-SPh, 4), 135 (25),
77 (6.5%).
8b: C18H24OS, oil. IR (film, ν, cm-1) 3025, 1725, 1500; 1H NMR: 7.15–6.75 (dd, J = 7Hz, 4H, Ph), 3.10 (m; 1H), 2.30
(m, 2H, CH2CO), 2.21 (3H, s, CH3Ph), 0.80–2.00 (m, 8H), 0.92 (s, 3H), 0.86 (s, 3H); MS: m/z 287 (M-1, 1.0), 258 (M-30, 100),
165 (M-SC6H4Me, 2), 135 (31), 91(4.3 %).
551

ACKNOWLEDGMENT
This work was supported by the National Natural Science Foundation of China (No. 20272043) and the Natural
Science Foundation of Zhejiang Province (No. 201015).
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