Diels-Alder reactions of acyclic α-cyano α,β-alkenones: a new approach to highly substituted cyclohexene system

Article abstract of DOI:10.1016/j.tet.2009.11.105

The Diels-Alder reactions of a variety of acyclic α-cyano α,β-unsaturated ketones 8 have been investigated. With the assistance of boron trichloride, these compounds were found to undergo the cycloaddition readily with dienes to give the corresponding add

Full text of DOI:10.1016/j.tet.2009.11.105

Tetrahedron 66 (2010) 871–877
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Diels–Alder reactions of acyclic
a-cyano a,b-alkenones: a new approach to highly
substituted cyclohexene system
,
c,
*
Prashanth K. Amancha a, Yi-Chun Lai a, I-Chia Chen b, Hsing-Jang Liu a , Jia-Liang Zhu
*
a Department of Chemistry, National Tsing Hua University, Hsinchu 300013, Taiwan
b Department of Cosmetic Applications and Management, Cardinal Tien College of Healthcare and Management, Taipei, Taiwan
c Department of Chemistry, National Dong Hwa University, No. 1. Sec. 2, Da Hsueh Rd., Shoufeng, Hualien 974, Taiwan
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 6 July 2009
Received in revised form 26 November 2009
Accepted 26 November 2009
Available online 3 December 2009
The Diels–Alder reactions of a variety of acyclic
a-cyano a,b-unsaturated ketones 8 have been
investigated. With the assistance of boron trichloride, these compounds were found to undergo the
cycloaddition readily with dienes to give the corresponding adducts 9 in good to high yields. In addition,
some of 9 could be further subjected to the reductive alkylation reactions using lithium naphthalenide
(LN) and an appropriate alkylating agent, thus allowing for the generation of highly substituted cyclo-
hexenes 10 with the replacement of the cyano group with an alkyl substituent.
Keywords:
Diels–Alder reactions
Ó 2009 Elsevier Ltd. All rights reserved.
a
-Cyano a,b-unsaturated ketones
Boron trichloride
Lithium naphthalenide
Reductive alkylation
1. Introduction
agent (RX), thereafter tactically allowing for the installation of an
alkyl group to the ring junction position in providing 5 and 6. The
The Diels–Alder cycloaddition of
a
,
b
-unsaturated ketones with
combination of cycloaddition with reductive alkylation had there-
fore practically turned 1 and 2 into the synthetic equivalents of
their 2-alkyl substituted counterparts, which always show to be
less reactive in Diels–Alder reactions. So far, we have successfully
applied this strategy into the total syntheses of a few clerodane
diterpenoid natural products.5,6
dienes is a very useful method for forming substituted cyclo-
hexenes.1,2 For these substrates, it is well known that their re-
activity toward electron-rich dienes could be enhanced with the aid
of an
a electron-withdrawing activating group. Predictably, the
synthetic utility of the Diels–Alder reactions will be expanded if
those activating groups are amendable to further elaboration after
the cycloadditions. In our long-term research efforts directed to the
Diels–Alder chemistry, we have recently developed an efficient and
versatile synthetic route leading to the fused bicyclic ring systems
bearing an angular alkyl group based on the Diels–Alder reactions
of 2-cyano 2-cycloalkenones 1 and 2-cyano-2,5-cyclohexa-dien-
ones 2. It was found that with the activation by a nitrile function-
ality, the cycloadditions of 1 and 2 with various dienes took place
smoothly in a highly regio- and/or stereoselective manner to pro-
duce bicycles 3 and 4 possessing up to four stereogenic centers
(Scheme 1).3,4 Moreover, the angular cyano group of the resulting
adducts could be reductively cleaved by using lithium naph-
thalenide (LN) as a reducing reagent, and subsequently, the in situ
generated enolates were able to be trapped with an alkylating
Scheme 1. Diels–Alder reactions of 1 and 2 and reductive alkylation of the resulting
adducts.
Following the studies of 1 and 2, we were continuously in-
terested in applying the strategy to their acyclic analogs for pre-
paring substituted mono cyclohexenes. Herein we wish to report
* Corresponding authors. Tel.: þ886 3 8633583; fax: þ886 3 8633570.
E-mail addresses: hjliu@mx.nthu.edu.tw (H.-J. Liu), jlzhu@mail.ndhu.edu.tw
(J.-L. Zhu).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.11.105

872
P.K. Amancha et al. / Tetrahedron 66 (2010) 871–877
our findings on the Diels–Alder reactions of acyclic
unsaturated ketones as well as the reductive alkylation reactions of
the resulting adducts. Although there are numerous examples
a
-cyano
a
,
b
-
(TiCl4), the desired cycloaddition did not occur in CH2Cl2 at 0 ꢀC or
under refluxing conditions (Table 1, entries 1 and 2). Still with TiCl4,
the adduct 9a was formed in 50% yield only when the reaction was
carried out in refluxing benzene (entry 3). Similarly, the use of tin
reported on the Diels–Alder reactions of acyclic
ketones bearing an
activating substituent, such as ester,7 chloro,8
sulfonyl,9 bromo,10 or fluoro11 functional groups, to our knowledge,
a,b-unsaturated
a
Table 2
BCl3-mediated Diels–Alder reactions of 8 with dienes
the detailed studies on the acyclic
have never been reported before.
a-cyano a,b-unsaturated ketones
2. Results and discussion
The
studies were easily prepared by the Knoevenagel condensation
between aldehydes or ketones and -ketonitriles 7a–e, which were
a-cyano a,b-unsaturated ketones used for the current
Entry
1d
Substrate
Diene
Adduct
Yield (%)a
b
either commercially available (7d and 7e) or synthesized by the
base-mediated acylation of acetonitrile with the corresponding
esters (7a–c).12 As shown in Scheme 2, the condensation reactions
were all carried out in alcoholic solution under the catalysis of
8a
75
L
-proline for 24 h, to yield 8a–h in high yields (82–99%).13 For those
reactions with aldehydes, only the single E-isomers were produced
(8a–d, 8f, and 8h) and their stereogeometries were confirmed ei-
ther by NOE experiments (8a–c, 8f) or by X-ray analysis (8d and
8h). We thus obtained the dienophilic substrates with considerable
structural diversity and used them for the following study.
2
3
8b
8c
86
82
4b
8d
62
Scheme 2. Preparation of a-cyano a,b-unsaturated ketones.
5b,c
8e
8f
64
68
65
Our previous studies on 1 and 2 revealed that their Diels–Alder
reactivity as well as the regio- and/or stereoselectivity of the re-
actions could be greatly enhanced by the assistance of the Lewis
acid.3,4 Therefore, in the current investigation, several Lewis acids
traditionally used for the activation of dienophiles were initially
screened by the reaction of 8f with 2,3-dimethyl-1,3-butadien
(Table 1). It was found that with the use of titanium (IV) chloride
6d
Table 1
Optimization of Lewis acid-mediated reaction conditions
7c
8g
Entry
Reaction conditions
TiCl4/CH2Cl2/0 ꢀ
TiCl4/CH2Cl2/reflux
TiCl4/benzene/reflux
SnCl4/CH2Cl2/reflux
SnCl4/benzene/reflux
ZnCl2/benzene/reflux
Time (h)
Yielda (%)
1
2
3
4
5
6
7
8
9
C
56
56
48
56
48
48
36
24
24
d
d
50
d
65
68
78
80
81
8d
8h
88
BF3$OEt2/CH2Cl2/25 ꢀ
BCl3/CH2Cl2/25 ꢀ
BCl3/benzene/25 ꢀ
C
a
Yield refers to purified product.
Only single diastereoisomer was formed.
The regiochemistry (ortho-like for 9f and para-like for 9h) was determined by
b
c
C
C
1H–1H COSY experiment.
a
Isolated yield.
d
The structure was confirmed by X-ray analysis.

P.K. Amancha et al. / Tetrahedron 66 (2010) 871–877
873
Table 3
(IV) chloride (SnCl4) gave no detectable formation of the product in
LN-Induced reductive alkylation reactions of 9a, 9h, and 9i
CH2Cl2 (entry 4) and 65% of 9a in refluxing benzene (entry 5). It was
also noted that in refluxing benzene, zinc chloride (ZnCl2) displayed
a comparable capability in promoting the reaction as TiCl4 and
SnCl4 to afford 9a in 68% yield (entry 6). We further discovered that
the use of boron-containing Lewis acids, i.e., boron trifluoride
etherate (BF3$OEt2) and boron trichloride (BCl3) in CH2Cl2 could
result in the formation of 9a in much higher yields under the rel-
atively milder reaction conditions (entries 7 and 8) and moreover,
BCl3 appeared to be even better than BF3$OEt2 in term of permitting
a shorter time for the reaction to attain the completion. With BCl3,
we also observed that the replacement of CH2Cl2 with benzene
almost caused no improvement on the yield of 9a (entry 9). Con-
sidering the higher toxicity of benzene than CH2Cl2, we therefore
applied the reaction conditions indicated in entry 8 to the sub-
strates 8a–h (Table 2).
Entry
1b
Substrate
Product
Yielda (%)
9a
80
72
Under the standard reaction conditions (Table 1, entry 8), the
cyclization reactions of 8a–h with a range of dienes including 2,3-
dimethyl-1,3-butadiene (Table 2, entries 1 and 3), cyclohexa-1,3-
diene (entry 2), 2,4-hexadiene (entry 4), trans-1,3-pentadiene
(entry 5) or isoprene (entries 6–8) occurred smoothly in giving the
formation of the corresponding adducts 9b–i in good to high yields
(62–88%). From the results in Table 2, it seems to be difficult to
reach the formidable conclusion on the correlation between the
2b
9a
9h
3
68
88
b
substitution of 8 and their reactivity. Even though, the results in
entries 1 and 3 (2,3-dimethyl-1,3-butadiene) as well as entries 6–8
(isoprene) may imply that the 2-furyl group is more effective than
phenyl and cyclohexyl groups at strengthening the reactivity of the
dienophile. Besides, the generation of the single diastereomers 9e
and 9f in entries 4 and 5 suggests that the cycloadditions should
proceed in a stereo-controlled fashion. The NOE experiments of 9e
confirmed that it was produced in an endo-to-keto route as evi-
denced by the correlations between the methine protons at the C-2,
C-5, and C-6 positions (Fig. 1). Based on this and previous experi-
ences,3,4 we envisioned that adduct 9f should also be produced in
the same endo transition state, albeit its NOE and NOESY spectra
failed to show any diagnostic signals. It is also worthy to note that
the cycloaddition reactions strictly followed the para- or ortho-like
rule as indicated by the exclusive formation of 9f–i as the single
regioisomers. In this manner, we were thus able to achieve a series
of cyclohexene derivatives with high functionalities.
4c
9i
a
Yield refers to purified product.
b
Only single diastereoisomer was formed. The stereochemistry was determined
by NOE experiments.
c
The structure was confirmed by X-ray analysis.
While compounds 9b–f failed for the reductive methylation, the
reductive decyanation of 9d could occur upon the sequential
treatment with LN and an aqueous ammonium chloride solution, to
give compound 1115 in 70% yield (Scheme 3). We thus speculated
that interference of
a acidic proton(s) of the carbonyl group to the
initially formed enolate intermediates might account for the failure
of 9b–f. To prove this, we further performed a deuterium in-
corporation experiment with 9b by treating it with LN (ꢁ45 ꢀC,
45 min) and then D2O. However, the reaction only produced
a complex mixture and the 13C NMR spectra of the major compo-
nent did not display any carbonyl carbon signal, implying that the
carbonyl group might be reduced. Currently, the exploration for the
true reason is still underway in our group.
Figure 1. NOE correlations of 9e.
After completing the investigation on the Diels–Alder reactions,
we further surveyed the possibility of applying the resulting ad-
ducts into the reductive alkylation process according to the estab-
lished protocol.3,4 It was found that the subjection of 9b–f to the
reduction alkylation conditions with lithium naphthalenide (LN)14
and methyl iodide gave no desired methylated products but only
complex mixtures, whereas 9a, 9h, and 9i could undergo the re-
ductive methylation and allylation reactions easily. As shown in
Table 3, treatment of 9a, 9h and 9i with LN in THF at ꢁ45 ꢀC for
45 min followed by the addition of methyl iodide or allyl bromide
to the reaction mixtures led to the generation of alkylated products
10a–d in fairly good yields (68–88%).
Scheme 3. Reductive decyanation of 9d.
3. Conclusion
In conclusion, we have demonstrated that with the assistance of
BCl3, 8 could undergo the Diels–Alder reactions easily with the
electron-rich dienes to provide the adducts with wide structural
diversity in good yields. Besides, the high regio- and/or stereo-
selectivity were observed for these reactions. In regards of these, as

874
P.K. Amancha et al. / Tetrahedron 66 (2010) 871–877
well as the convenient access to the starting materials and the great
potential in the elaboration of cyano and keto functionalities, it is
reasonable to believe that this protocol will be of considerable use
in synthetic chemistry. In addition, we have further proved that the
cyano group of the products with t-butyl and phenyl keto moieties
could be replaced by an alkyl group through a simple reductive
alkylation operation, to result in the generation of a few com-
pounds, which are otherwise difficult to be achieved. Currently, the
application of this method into the syntheses of more complex
molecules is being explored by us.
(0.60 g, 5.20 mmol, 0.2 equiv), and 2-furfural (2.5 g, 26.02 mmol,
1.0 equiv). Flash chromatography on silica gel (hexane–EtOAc 8:2)
gave 8c as a yellow solid (3.92 g, 86%).
1H NMR (400 MHz, CDCl3):
d
7.94 (d, J¼2.4 Hz, 1H), 7.74 (d,
J¼2.0 Hz, 1H), 7.94 (d, J¼3.2 Hz, 1H), 6.65 (dd, J¼3.6, 3.6 Hz, 1H),
2.91 (q, J¼7.2 Hz, 2H), 1.18 (t, J¼7.2 Hz, 3H); 13C NMR (100 MHz,
CDCl3):
d 193.6 (CO), 148.9 (C), 148.3 (CH), 136.8 (CH), 122.3 (CH),
116.9 (CN), 113.9 (CH), 104.7 (C), 33.6 (CH2), 7.6(CH3); IR (neat):
3133, 3037, 2978, 2212, 1695, 1608, 1534, 1167 cmꢁ1; HRMS (EI)
calcd for C10H9NO2: 175.0633; found: 175.0633.
4. Experimental
4.1. General
4.2.4. (E)-2-(Cyclopropanecarbonyl)-3-(naphthalen-2-yl)-acryloni-
trile (8d). The typical procedure for the preparation of 8a was fol-
lowed using 3-cyclopropyl-3-oxopropanenitrile (1.75 g,16.00 mmol,
1.0 equiv), L-proline (0.37 g, 3.20 mmol, 0.2 equiv), and 2-naphthal
All of starting materials were obtained from commercial sup-
pliers and used without further purification. Diels–Alder and re-
ductive alkylation reactions were all performed under an
atmosphere of argon. Tetrahydrofuran was distilled from sodium–
benzophenone, and dichloromethane and benzene were distilled
from calcium hydride before use. TLC analysis was performed on
Merck 25 DC-Alufolien Kieselgel 60F254 aluminum-backed plates
and visualized by UV or permanganate treatment. All of the com-
pounds were purified by flash chromatography on Merck Art.9385
Kieselgel 60 silica gel (230–400 mesh). NMR spectra (1H, 13C, DEPT,
COSY) were recorded on a Varian Unity 400 or a Bruker DMX-600
spectrometer using deuterio-chloroform (CDCl3) as solvent. High-
resolution mass spectra (HRMS) were determined by using a JEOL
JMS-HX110 high-resolution mass spectrometer in an electron im-
pact (EI, 70 eV) mode. The X-ray analyses were carried out on
a Bruker SMART APEX instrument.
(2.5 g, 16.00 mmol, 1.0 equiv). Flash chromatography on silica gel
(hexane–EtOAc 9.5:0.5) gave 8d as a yellow crystal (3.76 g, 95%).
1H NMR (400 MHz, CDCl3):
d
8.39 (s, 1H), 8.30 (s, 1H), 8.20 (d,
J¼8.8 Hz, 1H), 7.94–7.85 (m, 3H), 7.63–7.53 (m, 2H), 2.76–2.69 (m,
1H), 1.30–1.10 (m, 4H); 13C NMR (100 MHz, CDCl3):
193.4 (CO),
d
152.2 (CH), 135.2 (C), 134.4 (CH), 132.6 (C), 129.2 (CH), 129.0 (CH),
128.9 (CH), 127.7 (CH), 127.0 (CH), 125.1 (CH), 117.8 (CN), 109.3 (C),
18.5 (CH), 13.2 (CH2), 13.2 (CH2); IR (neat): 3057, 3010, 2212, 1678,
1578, 1384, 1146 cmꢁ1; HRMS (EI) calcd for C17H13NO: 247.0997;
found: 247.1002.
4.2.5. 2-(Cyclopropanecarbonyl)-3-methylbut-2-enenitrile (8e). The
typical procedure for the preparation of 8a was followed using
3-cyclopropyl-3-oxopropanenitrile (2.0 g, 18.33 mmol, 1.0 equiv),
L-proline (0.42 g, 3.67 mmol, 0.2 equiv), and acetone (1.35 mL,
18.4 mmol, 1.0 equiv). Flash chromatography on silica gel (hexane–
EtOAc 9:1) gave 8e as a yellow oil (2.46 g, 90%).
4.2. General procedure for Knoevenagel condensation for the
preparation of 8
1H NMR (400 MHz, CDCl3):
d
2.47–2.44 (m, 1H), 2.25 (s, 3H), 2.24
(s, 3H), 1.07–0.96 (m, 4H); 13C NMR (100 MHz, CDCl3):
d
194.9 (CO),
170.7 (C), 117.3 (CN), 112.3 (C), 27.1 (CH3), 22.9 (CH3), 20.2 (CH), 12.4
(CH2); IR (KBr): 3012, 2214, 1685, 1586, 1384, 1164 cmꢁ1; HRMS (EI)
calcd for C9H11NO: 149.0841; found: 149.0849.
4.2.1. (E)-2-Benzylidene-3-oxobutanenitrile (8a). To a solution of 3-
oxobutanenitrile (1.96 g, 23.56 mmol, 1.0 equiv) in 30 mL of absolute
ethanol, L-proline (0.54 g, 4.71 mmol, 0.2 equiv) and benzaldehyde
(2.5 g, 23.56 mmol, 1.0 equiv) were successively added. The resulting
reaction mixture was stirred at room temperature for 24 h and then
concentrated in vacuo. The crude residue was subjected to chro-
matographic purification on silica gel (hexane–EtOAc 9.5:0.5) to give
3.63 g of 8a as a white solid (90%).
4.2.6. (E)-2-Benzylidene-4,4-dimethyl-3-oxopentanenitrile (8f). The
typical procedure for the preparation of 8a was followed using 4,4-
dimethyl-3-oxopentanenitrile (2.95 g, 23.56 mmol, 1.0 equiv),
L-proline (0.54 g, 4.71 mmol, 0.2 equiv), and benzaldehyde (2.5 g,
23.56 mmol,1.0 equiv) Flash chromatography on silica gel (hexane–
1H NMR (400 MHz, CDCl3):
d
8.12 (s, 1H), 7.99 (d, J¼8.0 Hz, 2H),
EtOAc 9:1) gave 8f as a white solid (4.97 g, 99%).
7.57–7.47 (m, 3H), 2.56 (d, J¼1.2 Hz, 2H); 13C NMR (100 MHz,
1H NMR (400 MHz, CDCl3):
d
8.18 (s, 1H), 7.96–7.93 (m, 2H),
CDCl3):
d
190.9 (CO), 152.7 (CH), 133.1 (CH), 131.1 (C), 130.9 (CH),
7.50–7.41 (m, 3H), 1.38 (s, 9H); 13C NMR (100 MHz, CDCl3):
d
197.9
128.9 (CH), 116.7 (CN), 109.6 (C), 27.3 (CH3); IR (neat): 2925, 2854,
(CO), 156.0 (CH), 132.8 (CH), 131.9 (C), 131.0 (CH), 129.0 (CH), 118.1
(CN), 107.2 (C), 44.5 (C), 26.3 (CH3); IR (neat): 2973, 2232, 1704,
1583, 1456 cmꢁ1; HRMS (EI) calcd for C14H15NO: 213.1154; found:
213.1161.
2218, 1777, 1382, 1598 cmꢁ1
171.0684; found: 171.0678.
; HRMS (EI) calcd for C11H9NO:
4.2.2. (E)-2-Benzylidene-3-oxopentanenitrile (8b). The typical pro-
cedure for the preparation of 8a was followed using 3-oxopenta-
4.2.7. 2-Cyclohexylidene-4,4-dimethyl-3-oxopentanenitrile
(8g). The typical procedure for the preparation of 8a was followed
using 4,4-dimethyl-3-oxopentanenitrile (1.96 g, 19.97 mmol,
1.0 equiv), L-proline (0.46 g, 3.99 mmol, 0.2 equiv), and cyclohexa-
none (2.5 g, 19.97 mmol, 1.0 equiv). Flash chromatography on silica
nenitrile (2.29 g, 23.56 mmol, 1.0 equiv),
L-proline (0.54 g,
4.71 mmol, 0.2 equiv), and benzaldehyde (2.5 g, 23.56 mmol,
1.0 equiv). Flash chromatography on silica gel (hexane–EtOAc 8:2)
gave 8b as a white solid (4.27 g, 98%).
1H NMR (400 MHz, CDCl3):
d
8.17 (s, 1H), 7.99 (d, J¼7.6 Hz, 2H),
gel (hexane–EtOAc 9.5:0.5) gave 8g as a colorless oil (3.36 g, 82%).
7.55–7.24 (m, 3H), 2.96 (q, J¼7.2 Hz, 2H), 1.22 (t, J¼7.2 Hz, 3H); 13C
1H NMR (400 MHz, CDCl3):
d
2.56 (t, J¼6.2 Hz, 2H), 2.27 (t,
NMR (100 MHz, CDCl3):
d
193.8 (CO), 152.7 (CH), 133.2 (CH), 131.5
J¼5.8 Hz, 2H), 1.76–1.61 (m, 6H), 1.26 (s, 9H); 13C NMR (100 MHz,
(C),131.2 (CH), 129.2 (CH), 117.1 (CN),109.1 (C), 33.8 (CH2), 7.7 (CH3);
IR (neat): 3060, 2982, 2224, 1682, 1601, 1571, 1450 cmꢁ1; HRMS (EI)
calcd for C12H11NO: 185.0841; found: 185.0839.
CDCl3): d 204.1 (CO), 170.3 (C), 115.7 (CN), 107.8 (C), 45.3 (C), 34.8
(CH2), 32.3 (CH2), 28.1 (CH2), 27.9 (CH2), 26.7 (CH3), 25.4 (CH2); IR
(neat): 2938, 2862, 2212, 1697, 1609, 1478, 1450 cmꢁ1; HRMS (EI)
calcd for C13H19NO: 205.1467; found: 205.1465.
4.2.3. (E)-2-(Furan-2-ylmethylene)-3-oxopentanenitrile
typical procedure for the preparation of 8a was followed using
3-oxopentanenitrile (2.52 g, 26.02 mmol, 1.0 equiv), -proline
(8c). The
4.2.8. (E)-2-Benzoyl-3-(furan-2-yl)acrylonitrile (8h). The typical
procedure for the preparation of 8a was followed using 3-oxo-3-
L

P.K. Amancha et al. / Tetrahedron 66 (2010) 871–877
875
phenylpropanenitrile (3.78 g, 26.02 mmol, 1.0 equiv),
L-proline
CDCl3): d 202.6 (CO), 139.0 (C), 138.1 (CH), 128.6 (CH), 128.6 (CH),
(0.60 g, 5.20 mmol, 0.2 equiv), and 2-furfural (2.5 g, 26.02 mmol,
1.0 equiv). Flash chromatography on silica gel (hexane–EtOAc 7:3)
gave 8h as a yellow crystal (5.52 g, 95%).
128.4 (CH), 127.2 (CH), 120.1 (CN), 57.5 (C), 45.6 (CH), 37.8 (CH), 33.5
(CH), 32.0 (CH2), 22.8 (CH2), 17.8 (CH2), 8.5 (CH3); IR (neat): 3055,
2945, 2231, 1727, 1498, 1451, 1127 cmꢁ1; HRMS (EI) calcd for
C18H19NO: 265.1467; found: 265.1469.
1H NMR (400 MHz, CDCl3):
d
7.89 (s, 1H), 7.84–7.82 (m, 2H), 7.42
(d, J¼1.6 Hz, 1H), 7.60–7.55 (m, 1H), 7.48–7.45 (m, 3H), 6.66–6.65
(m, 1H); 13C NMR (100 MHz, CDCl3):
188.2 (CO), 148.9 (C), 148.5
d
4.3.4. 6-(Furan-2-yl)-3,4-dimethyl-1-propionylcyclohex-3-enecarbo-
nitrile (9d). The typical procedure for the preparation of 9a was
followed using 8c (1.2 g, 6.85 mmol, 1.0 equiv), boron trichloride
(5.14 mL, 5.14 mmol, 0.75 equiv), and 2,3-dimethyl-1,3-butadiene
(3.1 mL, 27.40 mmol, 4.0 equiv). Chromatographic purification on
silica gel (hexane–EtOAc 0.5:9.5) gave 9d as a colorless oil (1.44 g,
82%).
(CH), 140.2 (CH), 135.9 (C), 133.1 (CH), 128.9 (CH), 128.5 (CH), 122.2
(CH), 116.8 (CN), 114.0 (CH), 105.2 (C); IR (neat): 3149, 3115, 3032,
2208, 1664, 1582, 1461, 1278 cmꢁ1; HRMS (EI) calcd for C14H9NO2:
223.0633; found: 223.0633.
4.3. General procedure for BCl3-catalyzed Diels–Alder
reactions
1H NMR (600 MHz, CDCl3):
d
7.31 (d, J¼1.8 Hz, 1H), 6.30 (dd,
J¼3.3, 1.9 Hz, 1H), 6.21 (d, J¼3.3 Hz, 1H), 3.34 (dd, J¼12.3, 5.3 Hz,
1H), 2.79 (dd, J¼17.1, 1.9 Hz, 1H), 2.68–2.61 (m, 2H), 2.28–2.16 (m,
3H), 1.69 (s, 3H), 1.66 (s, 3H), 0.93 (t, J¼1.5 Hz, 3H); 13C NMR
4.3.1. 3,4-Dimethyl-6-phenyl-1-pivaloylcyclohex-3-ene carbonitrile
(9a). To a solution of 8f (1.2 g, 5.63 mmol, 1.0 equiv) in anhydrous
CH2Cl2 (50 mL), boron trichloride (1 M in hexane, 4.22 mL,
4.22 mmol, 0.75 equiv) was added slowly via a syringe at room
temperature under an atmosphere of argon and the resulting re-
action mixture was stirred for 30–45 min at room temperature. The
2,3-dimethyl-1,3-butadiene (2.55 mL, 22.51 mmol, 4.0 equiv) was
then introduced to the reaction mixture and the resulting solution
was stirred for 24 h at room temperature. The reaction mixture was
slowly poured into ice-cooled water (50 mL) and extracted with
CH2Cl2 (4ꢂ25 mL) and the combined organic layers were dried over
Na2SO4, filtered and then concentrated in vacuo. The crude products
were purified by flash chromatography on silica gel (hexane–EtOAc
9.5:0.5) to afford 9a as a colorless crystal (1.33 g, 80%).
(150 MHz, CDCl3): d 205.4 (CO),152.8 (C), 142.0 (CH), 125.1 (C), 121.4
(C), 119.8 (CN), 110.6 (CH), 107.2 (CH), 53.9 (C), 39.9 (CH), 39.4 (CH2),
35.1 (CH2), 33.9 (CH2), 18.6 (CH3), 18.5 (CH3), 7.4 (CH3); IR (KBr):
2981, 2941, 2240, 1723, 1455, 1380, 1149, 1111 cmꢁ1; HRMS (EI)
calcd for C16H19NO2: 257.1416; found: 257.1410.
4.3.5. 1-(Cyclopropanecarbonyl)-2,5-dimethyl-6-(naphthalene-2-
yl)cyclohex-3-ene carbonitrile (9e). The typical procedure for the
preparation of 9a was followed using 8d (1.2 g, 4.85 mmol,
1.0 equiv), boron trichloride (3.64 mL, 3.64 mmol, 0.75 equiv), and
2,4-hexadiene (2.21 mL, 19.41 mmol, 4.0 equiv). Chromatographic
purification on silica gel (hexane–EtOAc 0.5:9.5) gave 9e as a white
solid (1.01 g, 62%).
1H NMR (600 MHz, CDCl3):
d
7.33–7.22 (m, 5H), 3.44 (dd, J¼12.5,
5.2 Hz, 1H), 2.82 (dd, J¼15.2, 15.3 Hz, 1H), 2.68 (d, J¼16.8 Hz, 1H),
1H NMR (600 MHz, CDCl3):
d 7.90 (s,1H), 7.82–7.78 (m, 3H), 7.60–
2.35 (d, J¼16.8 Hz,1H), 2.23 (dd, J¼17.9, 4.9 Hz,1H), 1.72 (s, 3H), 1.67
7.43 (m, 3H), 5.94 (dt, J¼10.1, 3.4 Hz,1H), 5.57 (dt, J¼10.1,1.9 Hz,1H),
3.75 (d, J¼6.7 Hz, 1H), 3.03–2.99 (m, 1H), 2.75–2.71 (m, 1H), 2.56–
2.54 (m, 1H), 1.25 (d, J¼7.2 Hz, 3H), 1.14 (d, J¼7.6 Hz, 3H), 0.89–0.86
(m,1H), 0.80–0.78 (m,1H), 0.62–0.60 (m,1H), 0.36–0.35 (m,1H); 13C
(s, 3H), 0.91 (s, 9H); 13C NMR (150 MHz, CDCl3):
d 208.6 (CO), 139.5
(C), 129.0 (CH), 128.4 (CH), 127.8 (CH), 126.3 (C), 121.3 (C), 120.9
(CN), 52.0 (C), 46.5 (C), 45.8 (CH), 44.1 (CH2), 35.4 (CH2), 25.2 (CH3),
18.8 (CH3), 18.5 (CH3); IR (neat): 2973, 2913, 2232, 1702, 1477, 1453,
1078 cmꢁ1; HRMS (EI) calcd for C20H25NO: 295.1936; found:
295.1929.
NMR (150 MHz, CDCl3): d 205.3 (CO), 136.2 (C), 133.1 (CH), 132.3 (C),
127.9 (CH), 127.7 (CH), 127.7 (CH), 127.5 (CH), 127.4 (CH), 127.0 (CH),
126.1 (CH),125.8 (CH),121.3 (CN), 56.5 (C), 50.4 (CH), 39.9 (CH), 35.6
(CH), 20.1 (CH), 17.1 (CH3), 15.7 (CH3), 13.7 (CH2), 12.7 (CH2); IR
(neat): 3020, 2970, 2235, 1699, 1453, 1380, 1132 cmꢁ1; HRMS (EI)
calcd for C23H23NO: 329.1780; found: 329.1770.
4.3.2. 1-Acetyl-3,4-dimethyl-6-phenylcyclohex-3-enecarbonitrile
(9b). The typical procedure for the preparation of 9a was followed
using 8a (1.2 g, 7.01 mmol, 1.0 equiv), boron trichloride (BCl3)
(5.26 mL, 5.26 mmol, 0.75 equiv), and 2,3-dimethyl-1,3-butadiene
(3.17 mL, 28.04 mmol, 4.0 equiv). Chromatographic purification on
silica gel (hexane–EtOAc 0.5:9.5) afforded 9b as a white solid
(1.34 g, 75%).
4.3.6. 1-(Cyclopropanecarbonyl)-2,6,6-trimethylcyclohex-3-ene-
carbonitrile (9f). The typical procedure for the preparation of 9a
was followed using 8e (1.2 g, 8.04 mmol, 1.0 equiv), boron tri-
chloride (6.03 mL, 6.03 mmol, 0.75 equiv), and trans-1,3-penta-
1H NMR (600 MHz, CDCl3):
d
7.32–7.24 (m, 5H), 3.12 (dd, J¼12.2,
diene
(3.2 mL,
32.17 mmol,
4.0 equiv).
Chromatographic
5.2 Hz, 1H), 2.82 (d, J¼17.1 Hz, 1H), 2.75–2.70 (m, 1H), 2.26 (d,
J¼17.1 Hz, 1H), 2.21 (dd, J¼17.9, 4.7 Hz, 1H), 1.85 (s, 3H), 1.69 (s, 3H),
purification on silica gel (hexane–EtOAc 0.5:9.5) gave 9f as a col-
orless oil (1.12 g, 64%).
1.67 (s, 3H); 13C NMR (150 MHz, CDCl3):
d
202.8 (CO), 138.7 (C),
1H NMR (600 MHz, CDCl3):
d
5.65 (dt, J¼7.6, 2.5 Hz,1H), 5.42 (dd,
128.6 (CH), 128.0 (CH), 127.8 (CH), 125.8 (C), 121.2 (C), 120.4 (CN),
54.8 (C), 46.3 (CH), 39.8 (CH2), 36.2 (CH2), 29.4 (CH3), 18.5 (CH3),
J¼11.8, 1.2 Hz, 1H), 2.98–2.96 (m, 1H), 2.63–2.60 (m, 1H), 2.46–2.42
(m, 1H), 1.82–1.78 (m, 1H), 1.24 (s, 3H), 1.22–1.20 (m, 1H), 1.06–1.03
(m, 3H), 1.03 (d, J¼7.1, 3H), 0.90 (s, 3H); 13C NMR (150 MHz, CDCl3):
18.4 (CH3); IR (neat): 2915, 2862, 2236, 1721, 1455, 1358,1197 cmꢁ1
HRMS (EI) calcd for C17H19NO: 253.1467; found: 253.1461.
;
d
204.1 (CO), 128.8 (CH), 124.5 (CH), 120.0 (CN), 63.9 (C), 39.1 (CH2),
37.0 (C), 33.1 (CH), 27.6 (CH3), 21.8 (CH), 21.3 (CH3), 17.2 (CH3), 14.7
4.3.3. 3-Phenyl-2-propionylbicyclo[2.2.2]oct-5-ene-2-carbonitrile
(9c). The typical procedure for the preparation of 9a was followed
using 8b (1.2 g, 6.48 mmol, 1.0 equiv), boron trichloride (4.86 mL,
4.86 mmol, 0.75 equiv), and 1,3-cyclohexadiene (2.47 mL,
25.91 mmol, 4.0 equiv). Chromatographic purification on silica gel
(hexane–EtOAc 0.3:9.7) yielded 9c as a white solid (1.87 g, 86%).
(CH2),12.7 (CH2); IR (neat): 2969, 2232,1701,1458,1378,1127 cmꢁ1
HRMS (EI) calcd for C14H19NO: 217.1467; found: 217.1466.
;
4.3.7. 4-Methyl-6-phenyl-1-pivaloylcyclohex-3-enecarbonitrile
(9g). The typical procedure for the preparation of 9a was followed
using 8f (1.2 g, 5.63 mmol, 1.0 equiv), boron trichloride (4.22 mL,
4.22 mmol, 0.75 equiv), and isoprene (2.25 mL, 22.51 mmol,
4.0 equiv). Chromatographic purification on silica gel (hexane–
EtOAc 0.5:9.5) provided 9g as a colorless crystal (1.07 g, 68%).
1H NMR (600 MHz, CDCl3):
d 7.35–7.32 (m, 2H), 7.28–7.25 (m,
3H), 6.56 (dd, J¼8.0, 7.0 Hz, 1H), 6.04 (dd, J¼7.8, 6.7 Hz, 1H), 3.65 (s,
1H), 3.13–3.11 (m, 1H), 2.91–2.90 (m, 1H), 2.90–2.83 (m, 1H), 2.78–
2.75 (m, 1H), 2.38–2.34 (m, 1H), 2.23–2.18 (m, 1H), 1.51–1.46 (m,
1H), 1.33–1.30 (m, 1H), 1.14 (t, J¼7.4 Hz, 3H); 13C NMR (100 MHz,
1H NMR (600 MHz, CDCl3):
3H), 5.40 (dd, J¼3.5, 1.3 Hz, 1H), 3.48 (dd, J¼12.4, 5.1 Hz, 1H), 2.78 (t,
d
7.34 (d, J¼7.2 Hz, 2H), 7.26–7.20 (m,

876
P.K. Amancha et al. / Tetrahedron 66 (2010) 871–877
J¼15.3 Hz, 1H), 2.66–2.63 (m, 1H), 2.53 (dd, J¼17.0, 5.5 Hz, 1H), 2.34
(dd, J¼18.0, 4.9 Hz,1H),1.77 (s, 6H), 0.89 (s, 9H); 13C NMR (150 MHz,
4.4.2. 1-(1-Allyl-3,4-dimethyl-6-phenylcyclohex-3-enyl)-2,2-dime-
thylpropan-1-one (10b). The typical procedure for preparing 10a
was employed using 9a (0.1 g, 0.34 mmol, 1.0 equiv), lithium
naphthalenide (3.5 mL, 1.19 mmol, 3.5 equiv), and allyl bromide
(0.1 mL, 1.18 mmol, 3.5 equiv). Flash chromatography on silica gel
(hexane–EtOAc 0.2:9.8) afforded 10b as a colorless oil (80 mg, 72%).
CDCl3):
d 208.7 (CO), 139.5 (C), 134.8 (C), 129.1 (CH), 128.4 (CH),
127.8 (CH), 121.1 (CN), 115.9 (CH), 51.0 (C), 46.0 (C), 45.6 (CH), 38.5
(CH2), 34.1 (CH2), 25.2 (CH3), 23.1 (CH3); IR (neat): 2983, 2972,
2232, 1704,1397, 1368 cmꢁ1
281.1780; found: 281.1783.
; HRMS (EI) calcd for C19H23NO:
1H NMR (600 MHz, CDCl3):
d 7.16–7.06 (m, 5H), 5.67–5.63 (m,
1H), 5.01–4.93 (m, 2H), 3.29 (dd, J¼12.3, 5.3 Hz, 1H), 2.77 (d,
J¼16.6 Hz, 1H), 2.60–2.57 (m, 1H), 2.54 (dd, J¼13.2, 6.9 Hz, 1H), 2.38
(d, J¼16.6 Hz, 1H), 2.33 (dd, J¼13.1, 8.2 Hz, 1H), 2.04 (d, J¼18.0 Hz,
1H), 1.76 (s, 3H), 1.69 (s, 3H), 0.69 (s, 9H); 13C NMR (150 MHz,
4.3.8. 4-Methyl-1-pivaloylspiro[5.5]undec-3-ene-1-carbonitrile
(9h). The typical procedure for the preparation of 9a was followed
using 8g (1.2 g, 5.85 mmol, 1.0 equiv), boron trichloride (4.38 mL,
4.38 mmol, 0.75 equiv), and isoprene (2.34 mL, 23.38 mmol,
4.0 equiv). Chromatographic purification on silica gel (hexane–
EtOAc 0.5:9.5) yielded 9h as a colorless oil (1.04 g, 65%).
CDCl3):
d 217.2 (CO), 145.1 (C), 135.3 (CH), 129.3 (CH), 128.1 (CH),
126.3 (CH), 124.4 (C), 123.9 (C), 117.8 (CH2), 57.2 (C), 46.7 (CH), 46.1
(C), 43.4 (CH2), 35.6 (CH2), 33.3 (CH2), 26.8 (CH3), 19.9 (CH3), 18.6
(CH3); IR (neat): 3062, 3029, 2972, 2926, 1676, 1453, 1365,
1H NMR (600 MHz, CDCl3):
d
5.22 (dd, J¼7.3, 1.5 Hz, 1H), 2.54–
2.51 (m, 1H), 2.38–2.31 (m, 2H), 2.14–2.11 (m, 1H), 1.77–1.71 (m,
2H), 1.69 (s, 3H), 1.63–1.60 (m, 1H), 1.55–1.52 (m, 2H), 1.45–1.35 (m,
2H), 1.34 (s, 9H), 1.29–1.24 (m, 2H), 1.10–1.05 (m, 1H); 13C NMR
1056 cmꢁ1
310.2296.
; HRMS (EI) calcd for C22H30O: 310.2297; found:
(150 MHz, CDCl3):
d
208.9 (CO), 133.9 (C), 122.8 (CN), 115.1 (CH),
4.4.3. 1-(1,4-Dimethylspiro[5.5]undec-3-en-1-yl)-2,2-dimethylpro-
pan-1-one (10c). The typical procedure for preparing 10a was
employed using 9h (0.1 g, 0.37 mmol, 1.0 equiv), lithium naph-
thalenide (3.8 mL, 1.30 mmol, 3.5 equiv), and allyl bromide
(0.14 mL, 1.30 mmol, 3.5 equiv). Flash chromatography on silica
53.4 (C), 47.7 (C), 40.5 (C), 35.3 (CH2), 34.2 (CH2), 33.9 (CH2), 28.8
(CH2), 27.0 (CH3), 25.3 (CH2), 23.6 (CH3), 21.8 (CH2), 21.3 (CH2); IR
(neat): 2250, 1722, 1380, 1360 cmꢁ1; HRMS (EI) calcd for C18H27NO:
273.2093; found: 273.2089.
gel (hexane–EtOAc 0.2:9.8) afforded 10c as
a colorless oil
4.3.9. 1-Benzoyl-6-(furan-2-yl)-4-methylcyclohex-3-enecarbonitrile
(9i). The typical procedure for the preparation of 9a was followed
using 8h (1.2 g, 5.38 mmol, 1.0 equiv), boron trichloride (4.03 mL,
4.03 mmol, 0.75 equiv), and isoprene (2.15 mL, 21.5 mmol,
4.0 equiv). Chromatographic purification on silica gel (hexane–
EtOAc 0.5:9.5) offered 9i as a colorless crystal (1.38 g, 88%).
(65 mg, 68%).
1H NMR (600 MHz, CDCl3):
d
5.22 (dd, J¼2.9, 1.4 Hz, 1H), 2.70 (d,
J¼17.7 Hz, 1H), 2.23 (d, J¼18.0 Hz, 1H), 1.79–1.78 (m, 1H), 1.71 (d,
J¼18.0 Hz, 1H), 1.62 (s, 3H), 1.58–1.56 (m, 3H), 1.47–1.46 (m, 2H),
1.38–1.33 (m, 3H), 1.27 (s, 3H), 1.21 (s, 9H), 1.15–1.11 (m, 1H), 1.04–
0.98 (m, 1H); 13C NMR (150 MHz, CDCl3):
d 219.1 (CO), 132.0 (C),
1H NMR (600 MHz, CDCl3):
d
7.66–7.65 (m, 2H), 7.49 (dd, J¼7.3,
118.7 (CH), 54.6 (C), 47.3 (C), 39.2 (C), 35.2 (CH2), 34.6 (CH2), 33.0
(CH2), 29.4 (CH3), 29.1 (CH2), 26.0 (CH2), 23.6 (CH3), 22.1 (CH2), 21.8
1.0 Hz, 1H), 7.37–7.35 (m, 2H), 7.23 (dd, J¼1.7, 1.0 Hz, 1H), 6.24–6.22
(m, 2H), 5.46 (dd, J¼3.5, 1.9 Hz, 1H), 3.76 (dd, J¼11.7, 5.4 Hz, 1H),
2.92–2.88 (m, 1H), 2.75–2.67 (m, 2H), 2.40 (dd, J¼17.9, 5.1 Hz, 1H),
(CH2), 18.5 (CH3); IR (neat): 2929, 2867, 1682, 1454, 1366, 982 cmꢁ1
HRMS (EI) calcd for C18H30O: 262.2297; found: 262.2294.
;
1.79 (s, 3H); 13C NMR (150 MHz, CDCl3):
d 196.7 (CO),153.1 (C),141.9
(CH), 136.0 (C), 133.8 (C), 132.9 (CH), 128.3 (CH), 128.2 (CH), 119.9
(CN), 116.0 (CH), 110.4 (CH), 107.5 (CH), 51.2 (C), 39.8 (CH), 36.0
(CH2), 32.6 (CH2), 23.0 (CH3); IR (neat): 2969, 2914, 2855, 2237,
1686, 1597, 1236 cmꢁ1; HRMS (EI) calcd for C19H17NO2: 291.1259;
found: 291.1252.
4.4.4. 6-(Furan-2-yl-1,4-dimethylcyclohex-3-enyl)-phenyl-methanone
(10d). The typical procedure for preparing 10a was employed using
9i (0.1 g, 0.34 mmol, 1.0 equiv), lithium naphthalenide (3.5 mL,
1.19 mmol, 3.5 equiv) and methyl iodide (0.08 mL, 1.20 mmol,
3.5 equiv). Flash chromatography on silica gel (hexane–EtOAc
0.2:9.8) afforded 10d as a colorless crystal (85 mg, 88%).
1H NMR (600 MHz, CDCl3):
d
7.49–7.47 (m, 2H), 7.40 (t, J¼7.4 Hz,
4.4. General procedure for the reductive alkylation reactions
1H), 7.35–7.32 (m, 2H), 7.15 (d, J¼1.8 Hz, 1H), 6.19 (dd, J¼3.2, 1.8 Hz,
1H), 5.95 (d, J¼3.2 Hz 1H), 5.35 (t, J¼1.5 Hz, 1H), 3.60 (dd, J¼6.0,
2.9 Hz,1H), 2.52–2.47 (m, 2H), 2.29 (d, J¼18.6 Hz,1H), 2.03–1.99 (m,
4.4.1. 2,2-Dimethyl-1-(1,3,4-trimethyl-6-phenylcyclohex-3-enyl)pro-
pan-1-one (10a). To a solution of 9a (0.1 g, 0.34 mmol, 1.0 equiv) in
THF (5 mL) pre-cooled at ꢁ45 ꢀC, lithium naphthalenide THF so-
lution14 (0.34 M, 3.5 mL, 1.19 mmol, 3.5 equiv) was added via
a syringe under the protection of an argon atmosphere. The
resulting dark green solution was continued to stir at ꢁ45 ꢀC for
45 min and added with methyl iodide (0.07 mL, 1.19 mmol,
3.5 equiv). The reaction mixture was stirred at room temperature
for 12 h then poured into saturated NH4Cl aqueous solution
(10 mL) and extracted with EtOAc (2ꢂ20 mL). The combined or-
ganic extract was washed with saturated NaCl aqueous solution
(10 mL) and then concentrated. Chromatographic purification on
silica gel (hexane–EtOAc 0.2:9.8) afforded 10a as a colorless oil
(770 mg, 80%).
1H), 1.70 (s, 3H), 1.42 (s, 3H); 13C NMR (150 MHz, CDCl3):
d 208.8
(CO), 157.0 (C), 140.5 (CH), 139.7 (C), 131.0 (C), 130.4 (CH), 127.9 (CH),
127.3 (CH), 119.2 (CH), 110.1 (CH), 105.9 (CH), 48.8 (C), 39.9 (CH),
32.6 (CH2), 32.1 (CH2), 23.9 (CH3), 23.2 (CH3); IR (neat): 2960, 2911,
2846, 1672, 1500, 1441, 1274, 1169 cmꢁ1; HRMS (EI) calcd for
C19H20O2: 280.1463; found: 280.1467.
4.4.5. 1-[6-(Furan-2-yl)-3,4-dimethylcyclohex-3-enyl]-propan-1-one
(11). To a solution of 9d (0.16 g, 0.62 mmol, 1.0 equiv) in THF (8 mL)
pre-cooled at ꢁ45 ꢀC, lithium naphthalenide THF solution (0.34 M,
6.4 mL, 2.17 mmol, 3.5 equiv) was added via a syringe under the
protection of an argon atmosphere. The resulting dark green solu-
tion was continued to stir at ꢁ45 ꢀC for 45 min and quenched with
10% aqueous NH4Cl solution (20 mL). After the extraction with
EtOAc (2ꢂ25 mL), The combined organic extract was washed with
saturated NaCl aqueous solution (15 mL) and then concentrated.
Chromatographic purification on silica gel (hexane–EtOAc 0.5:9.5)
afforded 11 as a colorless oil (101 mg, 70%).
1H NMR (600 MHz, CDCl3):
d
7.16–7.08 (m, 5H), 3.32 (d, J¼6.9 Hz,
1H), 2.83 (d, J¼16.8 Hz, 1H), 2.57 (d, J¼18.4 Hz, 1H), 2.13 (d,
J¼8.4 Hz, 1H), 2.10 (d, J¼9.8 Hz, 1H), 1.72 (s, 3H), 1.68 (s, 3H), 1.25 (s,
3H), 0.87 (s, 9H); 13C NMR (150 MHz, CDCl3):
d 217.7 (CO), 145.0 (C),
129.0 (CH), 127.9 (CH), 126.2 (CH), 124.3 (C), 123.8 (C), 52.8 (C), 46.4
(CH), 46.1 (C), 37.2 (CH2), 35.5 (CH2), 27.3 (CH3), 26.1 (CH3), 19.8
(CH3), 18.6 (CH3); IR (neat): 2966, 2929, 1678, 1478, 1453, 1365,
988 cmꢁ1; HRMS (EI) calcd for C20H28O: 284.2140; found: 284.2146.
1H NMR (600 MHz, CDCl3):
J¼3.1, 1.9 Hz, 1H), 5.91 (d, J¼3.1 Hz, 1H), 3.55–3.53 (m, 1H), 2.90–
2.87 (m, 1H), 2.47–2.41 (m, 2H), 2.35–2.28 (m, 2H), 2.14 (dd, J¼17.5,
d
7.22 (d, J¼1.4 Hz, 1H), 6.22 (dd,

P.K. Amancha et al. / Tetrahedron 66 (2010) 871–877
877
4.3, 1H), 2.05 (dd, J¼7.5, 4.3, 1H), 1.65 (s, 3H), 1.62 (s, 3H), 1.0 (t,
References and notes
J¼7.1 Hz, 3H); 13C NMR (150 MHz, CDCl3):
d 212.4 (CO), 153.3 (C),
1. (a) Fringuelli, F.; Taticchi, A. Dienes in the Diels–Alder Reaction; Wiley: New York,
NY, 1990; (b) Paquette, L. A. Comprehensive Organic Synthesis; Pergamon: Ox-
ford, 1991; Vol. 5.
2. For recent examples, see: (a) Kraft, P.; Popaj, K. Eur. J. Org. Chem. 2008, 2, 261;
(b) Rickerby, J.; Vallet, M.; Bernardinelli, G.; Viton, F.; Ku¨ndig, E. P. Chem.d Eur. J.
2007, 13, 3354 and references cited therein.
140.7 (CH), 124.1 (C), 123.3 (C), 110.1 (CH), 105.3 (CH), 49.3 (CH),
35.2 (CH2), 35.0 (CH), 33.9 (CH2), 30.2 (CH2), 19.0 (CH3), 18.9 (CH3),
7.8 (CH3); IR (neat): 2976, 2916, 1710, 1672, 1450, 1337, 1009 cmꢁ1
HRMS (EI) calcd for C15H20O2: 232.1463; found: 232.1461.
;
3. Zhu, J. L.; Shia, K. S.; Liu, H. J. Chem. Commun. 2000, 1599.
4. Liu, H. J.; Yip, J. Synlett 2000, 1119.
Acknowledgements
5. Wu, J. D.; Shia, K. S.; Liu, H. J. Tetrahedron Lett. 2001, 42, 4207.
6. Liu, H. J.; Ho, Y. L.; Wu, J. D.; Shia, K. S. Synlett 2001, 1805.
7. (a) Kraus, G. A.; Roth, B. J. Org. Chem. 1980, 45, 4825; (b) Aguilar, R.; Reyes, A.;
Tamariz, J. Tetrahedron Lett. 1987, 28, 865; (c) Inokuchi, T.; Okano, M.; Miyamoto,
T. J. Org. Chem. 2001, 66, 8059.
8. Stork, G.; Borowitz, I. J. J. Am. Chem. Soc. 1960, 82, 4307.
9. Weichert, A.; Hoffmann, H.; Martin, H. R. J. Org. Chem. 1991, 56, 4098.
10. Bella, M.; Cianflone, M.; Montemurro, G.; Passacantilli, P.; Piancatelli, G. Tetra-
hedron 2004, 60, 4821.
11. Essers, M.; Ernet, T.; Haufe, G. J. Fluorine Chem. 2003, 121, 163.
12. Ji, Y.; Trenkle, W. C.; Vowles, J. V. Org. Lett. 2006, 8, 1161.
13. Hayashi, Y.; Yamaguchi, J.; Shoji, M. Tetrahedron 2002, 58, 9839.
14. For preparing a stock solution of LN, see: Liu, H. J.; Yip, J.; Shia, K. S. Tetrahedron
Lett. 1997, 38, 2253.
We are grateful to the National Science Council of Republic of
China (Taiwan), National Tsing Hua University and National Dong–
Hwa University for financial support.
Supplementary data
Crystallographic diagrams of compounds 8d, 8h, 9a, 9b, 9g, 9i,
and NMR spectra (1H, 13C NMR and DEPT) of new compounds are
available. Supplementary data associated with this article can be
found in the online version, at doi:10.1016/j.tet.2009.11.105.
15. Only single diastereoisomer was formed. The stereochemistry remains to be
determined.