Titanium(IV) chloride-mediated ring cleavage and Michael addition of 3,3-dialkylcyclobutanones and 3-[(trimethylsilyl)methyl]-cyclobutanones

Article abstract of DOI:10.1248/cpb.60.793

β′-Chloro and β′,γ′-unsaturated trichlorotitanium enolates, which were formed in situ by titanium(IV) chloride-mediated ring cleavage of 3,3-dialkylcyclobutanones and 3-[(trimethylsilyl)methyl]cyclobutanones, reacted with enones to give Michael adducts wi

Full text of DOI:10.1248/cpb.60.793

June 2012
Note
Chem. Pharm. Bull. 60(6) 793–797 (2012)
793
Titanium(IV) Chloride-Mediated Ring Cleavage and Michael
Addition of 3,3-Dialkylcyclobutanones and 3-[(Trimethylsilyl)methyl]-
cyclobutanones
Ryosuke Okuno, Jun-ichi Matsuo,* and Hiroyuki Ishibashi
School of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University;
Kakuma-machi, Kanazawa 920–1192, Japan. Received February 20, 2012; accepted March 19, 2012
βꢀ-Chloro and βꢀ,γꢀ-unsaturated trichlorotitanium enolates, which were formed in situ by titanium(IV)
chloride-mediated ring cleavage of 3,3-dialkylcyclobutanones and 3-[(trimethylsilyl)methyl]cyclobutanones,
reacted with enones to give Michael adducts with keeping a labile βꢀ-chloro or βꢀ,γꢀ-unsaturated group.
Key words cyclobutanone; Michael addition; enone; ring cleavage
Facile ring expansion, ring contraction and ring cleav- group at the β′-position (like 2) and an easily isomerizable
age of cyclobutanones have been utilized in the synthesis of β′,γ′-unsaturated bond7,8) (like 5) has been unknown except for
target molecules.1–4) We recently found a new synthetic util- aldol reactions5,6) because such enolates are difficult to prepare
ity of cyclobutanones: β′-chloro or β′,γ′-unsaturated enolates from the parent carbonyl compounds. To investigate the ver-
were readily prepared by titanium(IV) chloride-mediated ring satility of these functionalized titanium enolates, we studied
cleavage of cyclobutanones. Thus, the four-membered ring their Michael addition9–11) with enones, and we report here the
of 3,3-dialkylcyclobutanone 1 was cleaved by treatment with results we obtained.
titanium(IV) chloride to form trichlorotitanium enolate 2 hav-
First, ring cleavage of 3,3-dialkylcyclobutanones followed
ing a tert-alkyl chloride group. The enolate 2 reacted with by Michael addition to enones was investigated (Table 1). Ad-
aldehyde to afford the corresponding aldol product 35) (Eq. dition of titanium(IV) chloride to a mixture of methyl vinyl
1). Also, ring cleavage of 3-[(trimethylsilyl)(TMS)methyl]- ketone (MVK) and 3,3-dimethylcyclobutanone 7 bearing a
cyclobutanone
4 with titanium(IV) chloride gave β′,γ′- (tert-butyldimethylsilyl)(TBS)methyl group at the 2-posi-
unsaturated titanium enolate 5, which reacted with aldehyde tion gave an expected Michael adduct 8a having a tert-alkyl
to give a β′,γ′-unsaturated aldol product 66) (Eq. 2). The re- chloride group in 69% yield (entry 1). Cyclobutanone 7 was
activity of an enolate bearing an easily eliminative chloride preferentially activated with titanium(IV) chloride in the pres-
ence of MVK though it was reported that enones reacted with
titanium(IV) chloride to form β-chloro enolate in the Michael-
aldol and the Morita–Baylis–Hillman reaction.12,13) The use of
two equivalents of MVK was required to obtain 8a efficiently
because
1-tert-butyldimethylsilyl-5-chloro-5-methylhexan-
3-one, which was formed by ring-cleavage of 7, was obtained
along with 8a in the case of using less than two equivalents
of enones. A similar reaction of 7 with pent-1-en-3-one (entry
2) and 5-phenylpent-1-en-3-one (entry 3) gave the correspond-
ing adducts 8b and 8c in 68% and 39% yields, respectively.
Though 3-methylpent-3-en-2-one also reacted with 7 to afford
8d in 53% yield (entry 4), cyclic enones such as cyclopente-
none and cyclohexenone did not give Michael adduct 8. These
Table 1. Titanium(IV) Chloride-Mediated Reaction of 7 and Enones to 8a)
Entry
R
R′
Conditions
8
Yield/%b)
°
1
2
3
4
Me
Et
H
H
−78 to −40 C, 2h
8a
8b
8c
8d
69
68
39
53
°
−40 to −18 C, 2h
°
−78 to −40 C, 1h
°
−78 to −40 C, 1h
(CH2)2Ph
Me
H
Me
a) Cyclobutanone 7 (1.0eq), enone (2.0eq), and TiCl4 (1.5eq) were used. b) Isolated yield.
The authors declare no conflict of interest.
*To whom correspondence should be addressed. e-mail: jimatsuo@p.kanazawa-u.ac.jp
© 2012 The Pharmaceutical Society of Japan

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Vol. 60, No. 6
Table 2. Titanium(IV) Chloride-Mediated Reaction of Various 3,3-Dialkylcyclobutanone 9 and MVKa)
Entry
1
9
Conditions
Yield/%b)
°
R=Me 9a
R=Et 9b
R=i-Pr 9c
−78 to 0 C, 3h
33
45
30
°
2
3
−40 to 0 C, 2h
−40 to rt, 4h
°
4
9d
−78 to −18 C, 2.5h
47
55
°
−78 to −40 C, 1.5h
5
9e
a) For conditions, see Table 1. b) Isolated yield.
Table 3. Titanium(IV) Chloride-Mediated Reaction of 3-[(Trimethylsilyl)-
results suggested that β-alkyl substituents of enones retarded
Michael addition of trichlorotitanium enolate.
methyl]cyclobutanones 11 with MVK to 12a)
3,3-Dimethylcyclobutanones 9a–c having
a monoalkyl
group such as a methyl, ethyl, or isopropyl group at the
2-position reacted with MVK to afford the corresponding β′-
chloro adducts 10a–c (Table 2, entries 1–3). The present ring
cleavage and Michael addition of 3,3-dialkylcyclobutanones
proceeded in the absence of the TBS group of 7, but Michael
adducts 10a–c were obtained in lower yields. Ring cleavage
of monoalkylcyclobutanones 9a–c required higher reaction
Entry
1
11
12
Yield/%b)
64
°
temperatures (0 C to rt) than in the case of 2-(TBSmethyl)-
cyclobutanone 7. The higher reaction temperatures might
cause side reactions (e.g., further Michael addition of 10 to
MVK). The cyclobutanone ring was cleaved regioselectively at
the more substituted C2–C3 bond,5,6,14,15) and the TBSmethyl
group at the 2-position of cyclobutanone facilitated ring cleav-
age of the cyclobutanone ring5) by stabilizing a bicyclobuto-
nium ion16) intermediate. In addition to 3,3-dimethylcyclobu-
tanones, 3,3-diethylcyclobutanone 9d also reacted with MVK
to give 10d with a hindered tert-alkyl chloride group (entry 4).
Ring cleavage of 2,2,3,3-tetramethylcyclobutanone (9e) took
2
3
58
44
°
place at a low temperature (−40 C) and the desired adduct
10e was obtained in 55% yield (entry 5).
Next, titanium(IV) chloride-mediated Michael addition
of 3-(TMSmethyl)cyclobutanone 11 with enones was inves-
tigated (Table 3). Treatment of a mixture of 11a and MVK
4
5
50
°
with titanium(IV) chloride at −78 C gave a Michael adduct
12a having a β′,γ′-unsaturated bond in 64% yield (entry 1).
42c)
°
Thus, ring cleavage of 11a took place at −78 C, and formed
trichlorotitanium enolate (like 5) smoothly reacted with
MVK at the same temperature. Isomerization of the double
bond of 12a to the more stable α′,β′-unsaturated one was not
observed. 2,2-Diethylcyclobutanone 11b, spirocyclobutanone
11c,d, and 2-monomethylcyclobutanone 11e also reacted with
°
a) Compound 11 (1.0eq), MVK (2.0eq), and TiCl4 (2.0eq) were used. b) Isolated
yield unless otherwise mentioned. c) Determined by 1H-NMR analysis.
titanium(IV) chloride and MVK at −78 C to afford the cor- and β′,γ′-unsaturated18) acyclic 1,5-diketones by using
responding Michael adducts 12b–e in 42–58% yields (entries titanium(IV) chloride. It is expected that the β′-chloro and
2–5).
β′,γ′-unsaturated trichlorotitanium enolates generated by the
In conclusion, 3,3-dialkylcyclobutanones and 3-(TMS- present method will react with other electrophilic compo-
methyl)cyclobutanones reacted with enones to give β′-chloro17) nents, and they offer a unique method for the synthesis of

June 2012
795
functionalized carbonyl compounds.
22.6, 26.2, 29.8, 30.5, 57.8, 74.4, 209.5; IR (CHCl3, cm−1) 1758;
high resolution (HR)-MS (FAB+) Calcd for C9H17O (m/z)
141.1279, Found 141.1269.
Experimental
General All melting points were determined on Yanagi-
3,3-Diethyl-2-methylcylobutanone (9d) Pale yellow oil:
moto micro melting point apparatus and are uncorrected. In- 1H-NMR (600MHz, CDCl3) δ 0.88 (t, J=7.6Hz, 3H), 0.91
1
frared spectra (IR) were recorded on Horiba IR-710. H-NMR (t, J=7.6Hz, 3H), 1.05 (d, J=7.6Hz, 3H), 1.27 (dq, J=14.3,
spectra were recorded on a JEOL JNM ECA600 (600MHz) or 7.6Hz, 1H), 1.54–1.66 (m, 2H), 1.82 (dq, J=14.3, 7.6Hz,
a JEOL JNM ECS400 (400MHz) spectrometer at room tem- 1H), 2.58 (dd, J=16.4, 2.1Hz, 1H), 2.67 (dd, J=16.4, 2.7Hz,
perature; chemical shifts (δ) are reported in parts per million 1H), 2.99 (qdd, J=7.6, 2.7, 2.1Hz, 1H); 13C-NMR (150MHz,
relative to tetramethylsilane. Splitting pattern are designated CDCl3) δ 8.6, 8.7, 9.3, 23.6, 31.4, 36.3, 54.6, 61.3, 211.3; IR
as s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet; (CHCl3, cm−1) 1770; HR-MS (FAB+) Calcd for C9H17O (m/z)
br, broad. 13C-NMR spectra were recorded on a JOEL JNM 141.1279, Found 141.1291.
ECA600 (150MHz) spectrometer with complete proton decou-
Typical Experimental Procedure for Titanium(IV)
pling. Chemical shifts are reported in parts per million relative Chloride-Mediated Reaction of 3,3-Dialkylcyclobutanones
to tetramethylsilane with the solvent resonance as the internal and Enones: Preparation of 5-{[(tert-Butyldimethyl)silyl]-
standard CDCl3. Analytical TLC was performed on Merck methyl}-8-chloro-8-methylnona-2,6-dione (8a) To a stirred
precoated TLC plates (silica gel 60 GF254, 0.25mm). Silica- solution of 3,3-dialkylcyclobutanone 7 (50.0mg, 0.221mmol,
gel column chromatography was carried out on silica gel 1.0eq) and methyl vinyl ketone (31.0mg, 0.442mmol, 2.0eq)
°
60N (Kanto Kagaku Co., Ltd., spherical, neutral, 63–210µm). in dry dichloromethane (4mL) was added at −78 C a 1.0M
Preparative thin-layer chromatography (PTLC) was carried solution of TiCl4 in dichloromethane (0.33mL, 1.5eq). The
°
°
out on silica gel Wakogel B-5F. All reactions were carried resulting mixture was stirred at −78 C for 1.0h and at −40 C
out under nitrogen in dried glassware with magnetic stirring. for 1.0h. The reaction was quenched by adding saturated so-
°
A solution of titanium(IV) chloride in dichloromethane (1M) dium hydrogen carbonate solution at −40 C, and the mixture
was purchased from Aldrich. 3,3-Dialkylcyclobutanones 7 was extracted with dichloromethane. The combined organic
and 9a–e were synthesized by cycloaddition of dichloroketene extracts were dried over anhydrous sodium sulfate, filtered,
with olefins, followed by reductive dechlorination of the di- and concentrated. The crude product was purified by column
chlorocyclobutanone according to the literature procedures.5,19) chromatography on silica gel (eluted with hexane/ether) to
1
3-[(Trimethylsilyl)methyl]cyclobutanones 11a–e were prepared afford 8a (50.7mg, 0.152mmol, 69%) as a colorless oil: H-
according to the literature procedures.6)
NMR (400MHz, CDCl3) δ −0.02 (s, 3H), −0.01 (s, 3H), 0.46
2,3,3-Trimethylcyclobutanone (9a) To a suspension of (dd, J=14.7, 7.3Hz, 1H), 0.87 (s, 9H), 0.93 (dd, J=14.7, 6.0Hz,
2-methyl-but-2-ene (492mg, 7.01mmol) and zinc–copper cou- 1H), 1.72 (s, 3H), 1.73 (s, 3H), 1.69–1.78 (m, 1H), 1.85 (dtd,
ple (1.37g) in dry ether (25mL) was added dropwise a solution J=16.0, 8.2, 6.0Hz, 1H), 2.12 (s, 3H), 2.35 (ddd, J=17.9, 8.2,
of trichloroacetyl chloride (0.71mL, 6.36mmol) in dry ether 6.9Hz, 1H), 2.44 (ddd, J=17.9, 8.2, 6.0Hz, 1H), 2.56–2.62 (m,
(10mL) for 1h, and the reaction mixture was refluxed for 18h. 1H), 2.90 (d, J=16.5Hz, 1H), 3.03 (d, J=16.5Hz, 1H); 13C-
The mixture was filtered through Celite pad and the filtrate NMR (150MHz, CDCl3) δ −5.9, −5.3, 13.4, 16.6, 26.4, 27.0,
was concentrated. The residue was diluted with ether, and the 30.0, 32.2, 32.7, 40.6, 47.6, 54.7, 67.4, 207.9, 210.0; IR (CHCl3,
ether solution was washed with brine, dried over anhydrous cm−1) 1710; HR-MS (electron ionization (EI)+) Calcd for
sodium sulfate, filtered, and concentrated. The crude product C17H33ClO2Si (m/z) 332.19384, Found 332.19328.
was purified by column chromatography on silica gel (silica
gel (30g), hexane) to afford 2,2-dichloro-3,3,4-trimethylcy- methyldeca-3,7-dione (8b) Colorless oil: 1H-NMR (600
clobutanone (610mg, 48%). MHz, CDCl3) δ −0.02 (s, 3H), −0.01 (s, 3H), 0.46 (dd,
6-{[(tert-Butyldimethyl)silyl]methyl}-9-chloro-9-
To a stirred mixture of the above mentioned 2,2-dichloro- J=14.8, 7.6Hz, 1H), 0.87 (s, 9H), 0.93 (dd, J=14.8, 6.2Hz,
cyclobutanone (587mg, 3.24mmol) and zinc–copper couple 1H), 1.04 (t, J=7.6Hz, 3H), 1.72 (s, 3H), 1.73 (s, 3H), 1.72–
(1.06g) in methanol (20mL) was added ammonium chloride 1.78 (m, 1H), 1.86 (dtd, J=14.1, 8.2, 5.8Hz, 1H), 2.33 (ddd,
°
(1.21g, 22.7mmol) at room temperature. After stirred at 45 C J=17.5, 8.2, 6.9Hz, 1H), 2.40 (q, J=7.6Hz, 2H), 2.38–2.44
for 4h, the reaction mixture was filtered through Celite pad, (m, 1H), 2.57–2.61 (m, 1H), 2.90 (d, J=16.5Hz, 1H), 3.04 (d,
and the filtrate was concentrated. The residue was diluted with J=16.5Hz, 1H); 13C-NMR (150MHz, CDCl3) δ −5.9, −5.3,
ether, and the ether solution was washed with brine, dried 7.7, 13.4, 16.5, 26.3, 27.0, 32.1, 32.6, 35.9, 39.2, 47.6, 54.6,
over anhydrous sodium sulfate, filtered, and concentrated. The 67.4, 210.0, 210.7; IR (CHCl3, cm−1) 2954, 2929, 1712; HR-MS
crude product was purified by column chromatography on direct analysis in real time (DART+) Calcd for C18H36ClO2Si
silica gel (silica gel (15g), pentane/ether=20:1) to afford 9a19) (m/z) 347.21731, Found 347.21802.
1
(134mg, 37%) as a colorless oil: H-NMR (600MHz, CDCl3)
6-{[(tert-Butyldimethyl)silyl]methyl}-9-chloro-9-methyl-
δ 1.01 (t, J=7.2Hz, 3H), 1.10 (s, 3H), 1.39 (s, 3H), 2.57 (dd, 1-phenyldeca-3,7-dione (8c) Colorless oil: 1H-NMR (600
J=16.5, 1.7Hz, 1H), 2.88 (dd, J=16.5, 2.7Hz, 1H), 2.98 (qdd, MHz, CDCl3) δ −0.03 (s, 3H), −0.02 (s, 3H), 0.43 (dd,
J=7.2, 2.7, 1.7Hz, 1H); 13C-NMR (150MHz, CDCl3) δ 8.1, J=14.8, 7.6Hz, 1H), 0.86 (s, 9H), 0.91 (dd, J=14.8, 6.2Hz,
22.6, 29.2, 29.3, 57.9, 69.4, 211.0; IR (CHCl3, cm−1) 1776.
1H), 1.71 (s, 3H), 1.71 (s, 3H), 1.71–1.76 (m, 1H), 1.83 (dtd,
2-Isopropyl-3,3-dimethylcyclobutanone (9c) Colorless J=14.1, 8.2, 6.2Hz, 1H), 2.30 (ddd, J=17.5, 8.2, 6.9Hz, 1H),
oil: 1H-NMR (600MHz, CDCl3) δ 0.87 (d, J=6.6Hz, 3H), 2.39 (ddd, J=17.5, 8.2, 6.2Hz, 1H), 2.54–2.59 (m, 1H), 2.70
1.10 (d, J=6.6Hz, 3H), 1.18 (s, 3H), 1.44 (s, 3H), 1.87−1.95 (t, J=7.6Hz, 2H), 2.88 (t, J=7.6Hz, 2H), 2.88 (d, J=16.8Hz,
(m, 1H), 2.43 (d, J=15.8Hz, 1H), 2.54 (d, J=11.0Hz, 1H), 2.78 1H), 3.00 (d, J=16.8Hz, 1H), 7.16–7.20 (m, 3H), 7.26–7.29 (m,
(d, J=15.8Hz, 1H); 13C-NMR (150MHz, CDCl3) δ 21.0, 21.2, 2H); 13C-NMR (150MHz, CDCl3) δ −5.9, −5.3, 13.4, 16.6,

796
Vol. 60, No. 6
26.4, 26.9, 29.7, 32.1, 32.7, 39.9, 44.3, 47.6, 54.6, 67.4, 126.1, 2H), 3.02 (s, 2H); 13C-NMR (150MHz, CDCl3) δ 24.1, 29.9,
128.3, 128.5, 140.9, 209.2, 210.0; IR (CHCl3, cm−1) 1712; HR- 32.2, 32.7, 38.8, 47.2, 50.5, 67.8, 207.9, 211.3; IR (CHCl3,
MS (DART+) Calcd for C24H40ClO2Si (m/z) 423.24861, Found cm−1) 1720, 1702; HR-MS (EI+) Calcd for C12H21ClO2 (m/z)
423.24921.
232.12301, Found 232.12322.
5-{[(tert-Butyldimethyl)silyl]methyl}-8-chloro-3,8-
Typical Experimental Procedure for Titanium(IV)
dimethylnona-2,6-dione (8d) Pale yellow oil: 1H-NMR Chloride-Mediated Reaction of 3-[(Trimethylsilyl)methyl]-
(600MHz, CDCl3) δ −0.04 (s, 3H), −0.03 (s, 3H), 0.47 (dd, cyclobutanones and MVK: Preparation of 5,5-Dimethyl
J=14.8, 7.6Hz, 1H), 0.87 (s, 9H), 0.91 (dd, J=14.8, 5.8Hz, nona-8-ene-2,6-dione (12a) To a stirred solution of cy-
1H), 1.09 (d, J=6.9Hz, 3H), 1.20 (ddd, J=14.0, 7.9, 5.8Hz, clobutanone 11 (81.3mg, 0.441mmol, 1.0eq) and methyl vinyl
1H), 1.74 (s, 6H), 2.10 (ddd, J=14.0, 7.9, 5.8Hz, 1H), 2.17 ketone (61.8mg, 0.882mmol, 2.0eq) in dry dichloromethane
°
(s, 3H), 2.49 (dq, J=14.0, 6.9Hz, 1H), 2.52−2.57 (m, 1H), (4mL) was added at −78 C a 1.0M solution of TiCl4 in di-
2.92 (d, J=16.8Hz, 1H), 3.08 (d, J=16.8Hz, 1H); 13C-NMR chloromethane (0.88mL, 2.0eq), and the reaction mixture was
(150MHz, CDCl3) δ −5.8, −5.2, 13.9, 16.4, 16.6, 26.3, 28.2, stirred at the same temperature for 15min. The reaction was
32.1, 32.7, 36.0, 45.1, 46.4, 54.6, 67.4, 209.6, 211.8; IR (CHCl3, quenched with saturated aqueous sodium hydrogen carbon-
cm−1) 1710; HR-MS (DART+) Calcd for C18H36ClO2Si (m/z) ate solution at −78 C, and the mixture was extracted with
°
347.21731, Found 347.21758.
dichloromethane. The combined organic extracts were dried
8-Chloro-5,8-dimethylnona-2,6-dione
(10a) Colorless over anhydrous sodium sulfate, filtered, and concentrated.
1
oil: H-NMR (600MHz, CDCl3) δ 1.08 (d, J=7.2Hz, 3H), 1.62 The crude product was purified by column chromatography
(dtd, J=14.4, 8.2, 6.5Hz, 1H), 1.71 (s, 3H), 1.72 (s, 3H), 1.92 on silica gel (eluted with hexane/ether) to afford 12a (51.7mg,
(dtd, J=14.4, 8.2, 6.5Hz, 1H), 2.13 (s, 3H), 2.41 (ddd, J=17.5, 0.284mmol, 64%) as a colorless oil: 1H-NMR (600MHz,
8.2, 6.5Hz, 1H), 2.46 (ddd, J=17.5, 8.2, 6.5Hz, 1H), 2.62–2.68 CDCl3) δ 1.14 (s, 6H), 1.81 (t, J=7.6Hz, 2H), 2.13 (s, 3H),
(m, 1H), 2.94 (d, J=15.8Hz, 1H), 2.98 (d, J=15.8Hz, 1H); 2.33 (t, J=7.6Hz, 2H), 3.25 (dd, J=6.9, 1.4Hz, 2H), 5.10 (dd,
13C-NMR (150MHz, CDCl3) δ 16.1, 25.9, 29.9, 32.3, 32.6, 40.7, J=17.2, 1.4Hz, 1H), 5.16 (dd, J=10.3, 1.4Hz, 1H), 5.91 (ddt,
46.3, 54.7, 67.3, 208.2, 210.5; IR (CHCl3, cm−1) 1712; HR- J=17.2, 10.3, 6.9Hz, 1H); 13C-NMR (150MHz, CDCl3) δ
MS (DART+) Calcd for C11H20ClO2 (m/z) 219.11518, Found 24.2, 29.9, 32.8, 39.0, 41.6, 47.0, 118.1, 131.3, 208.1, 212.8; IR
219.11036.
(CHCl3, cm−1) 1708; HR-MS (EI+) Calcd for C11H18O2 (m/z)
8-Chloro-5-ethyl-8-methylnona-2,6-dione (10b) Color- 182.13068, Found 182.13048.
1
1
less oil: H-NMR (600MHz, CDCl3) δ 0.89 (t, J=7.2Hz, 3H),
5,5-Diethylnona-8-ene-2,6-dione (12b) Colorless oil: H-
1.44 (dtd, J=13.7, 7.6, 6.2Hz, 1H), 1.68 (dq, J=14.1, 7.2Hz, NMR (600MHz, CDCl3) δ 0.74 (t, J=7.6Hz, 6H), 1.54–1.65
2H), 1.72 (s, 3H), 1.73 (s, 3H), 1.87 (dtd, J=14.1, 8.2, 6.2Hz, (m, 4H), 1.82 (t, J=8.2Hz, 2H), 2.13 (s, 3H), 2.23 (t, J=8.2Hz,
1H), 2.12 (s, 3H), 2.37 (ddd, J=17.5, 8.6, 6.5Hz, 1H), 2.43 2H), 3.21 (dt, J=6.9, 1.4Hz, 2H), 5.08 (dd, J=17.2, 1.4Hz,
(ddd, J=17.5, 8.6, 6.2Hz, 1H), 2.48–2.52 (m, 1H), 2.92 (d, 1H), 5.14 (dd, J=10.3, 1.4Hz, 1H), 5.93 (ddt, J=17.2, 10.3,
J=16.5Hz, 1H), 2.99 (d, J=16.5Hz, 1H); 13C-NMR (150MHz, 6.9Hz, 1H); 13C-NMR (150MHz, CDCl3) δ 8.0, 25.4, 26.2,
CDCl3) δ 11.5, 23.8, 24.2, 29.9, 32.2, 32.6, 40.8, 53.3, 55.7, 26.3, 29.9, 38.2, 42.0, 54.0, 117.9, 131.5, 208.1, 212.9; IR
67.4, 208.2, 210.3; IR (CHCl3, cm−1) 1720, 1704; HR-MS (CHCl3, cm−1) 1710; HR-MS (DART+) Calcd for C13H23O2
(DART+) Calcd for C12H22ClO2 (m/z) 233.13083, Found (m/z) 211.16980, Found 211.16488.
233.12664.
5-Cyclopentyl-8-ene-2,6-dione (12c) Colorless oil: 1H-
8-Chloro-5-isopropyl-8-methylnona-2,6-dione
(10c) NMR (600MHz, CDCl3) δ 1.40–1.45 (m, 2H), 1.54–1.60 (m,
1
Colorless oil: H-NMR (600MHz, CDCl3) δ 0.86 (d, J=6.9Hz, 2H), 1.62–1.69 (m, 2H), 1.91 (t, J=8.2Hz, 2H), 2.04–2.09
3H), 0.97 (d, J=6.9Hz, 3H), 1.72 (s, 3H), 1.73 (s, 3H), (m, 2H), 2.11 (s, 3H), 2.28 (t, J=8.2Hz, 2H), 3.25 (dt, J=6.9,
1.73–1.77 (m, 1H), 1.83 (dtd, J=14.1, 8.9, 5.5Hz, 1H), 1.97 1.4Hz, 2H), 5.10 (dd, J=17.2, 1.4Hz, 1H), 5.14 (dd, J=10.3,
(qd, J=13.4, 6.9Hz, 1H), 2.11 (s, 3H), 2.29 (ddd, J=17.5, 8.9, 1.4Hz, 1H), 5.92 (ddt, J=17.2, 10.3, 6.9Hz, 1H); 13C-NMR
6.5Hz, 1H), 2.36–2.39 (m, 1H), 2.42 (ddd, J=17.5, 8.9, 5.5Hz, (150MHz, CDCl3) δ 24.9, 30.0, 31.2, 34.1, 39.7, 42.2, 59.5,
1H), 2.89 (d, J=16.8Hz, 1H), 3.00 (d, J=16.8Hz, 1H); 13C- 117.9, 131.6, 208.0, 211.8; IR (CHCl3, cm−1) 1708; HR-
NMR (150MHz, CDCl3) δ 18.8, 20.6, 21.7, 29.3, 29.9, 32.0, MS (DART+) Calcd for C13H21O2 (m/z) 209.15415, Found
32.7, 41.1, 56.7, 58.2, 67.4, 208.3, 210.2; IR (CHCl3, cm−1) 209.14967.
1712; HR-MS (DART+) Calcd for C13H24ClO2 (m/z) 247.14648,
Found 247.14192.
5-Cyclohexyl-8-ene-2,6-dione (12d) Colorless oil: 1H-
NMR (600MHz, CDCl3) δ 1.21–1.33 (m, 6H), 1.53–1.61 (m,
8-Chloro-8-ethyl-5-methyldeca-2,6-dione (10d) Color- 2H), 1.79 (t, J=7.9Hz, 2H), 1.98–2.05 (m, 2H), 2.10 (s, 3H),
less oil: 1H-NMR (600MHz, CDCl3) δ 0.98 (t, J=6.9Hz, 2.23 (t, J=7.9Hz, 2H), 3.24 (dd, J=6.9, 1.4Hz, 2H), 5.08 (dd,
3H), 0.98 (t, J=6.9Hz, 3H), 1.09 (d, J=6.9Hz, 3H), 1.61 (dtd, J=17.2, 1.4Hz, 1H), 5.15 (dd, J=10.3, 1.4Hz, 1H), 5.92 (ddt,
J=14.4, 8.2, 6.2Hz, 1H), 1.88–2.05 (m, 5H), 2.13 (s, 3H), 2.39 J=17.2, 10.3, 6.9Hz, 1H); 13C-NMR (150MHz, CDCl3) δ
(ddd, J=17.2, 8.2, 6.2Hz, 1H), 2.44 (ddd, J=17.2, 8.2, 6.2Hz, 22.8, 25.8, 30.0, 31.5, 33.0, 37.8, 41.6, 51.3, 118.0, 131.5, 208.0,
1H), 2.64 (qt, J=6.9, 6.2Hz, 1H), 2.67 (s, 2H); 13C-NMR 212.8; IR (CHCl3, cm−1) 1710; HR-MS (DART+) Calcd for
(150MHz, CDCl3) δ 8.8, 8.9, 16.4, 26.0, 29.9, 33.6, 33.8, 40.8, C14H23O2 (m/z) 223.16980, Found 223.16527.
46.3, 49.4, 76.5, 208.2, 210.7; IR (CHCl3, cm−1) 1720, 1704;
HR-MS (DART+) Calcd for C13H24ClO2 (m/z) 247.14648,
Found 247.14258.
Acknowledgment This work was supported in part by
a Grant-in-Aid for Scientific Research from the Ministry of
8-Chloro-5,5,8-trimethylnona-2,6-dione
less oil: H-NMR (600MHz, CDCl3) δ 1.13 (s, 6H), 1.73 (s,
6H), 1.79 (t, J=7.9Hz, 2H), 2.13 (s, 3H), 2.35 (t, J=7.9Hz,
(10e) Color- Education, Culture, Sports, Science and Technology of Japan.
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