Intramolecular Heck reaction strategy for the synthesis of functionalised tetrahydroanthracenes: A facile formal total synthesis of the linear abietane diterpene, umbrosone

Article abstract of DOI:10.1016/j.tetlet.2005.01.021

Rapid annulation employing an intramolecular Heck reaction yielded the functionalised 1,1,10-trimethyl-6-methoxy-1,2,3,4-tetrahydroanthracene 4a, a key intermediate for the linear diterpenoid quinone umbrosone (1), and the related compounds 4b-d. A simila

Full text of DOI:10.1016/j.tetlet.2005.01.021

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 1515–1519
Intramolecular Heck reaction strategy for the synthesis
of functionalised tetrahydroanthracenes: a facile formal
total synthesis of the linear abietane diterpene, umbrosone
Sujaya Sengupta, Ranjan Mukhopadhyay, Basudeb Achari and Asish Kr. Banerjee*
Division of Medicinal Chemistry, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Kolkata 700 032, India
Received 4 November 2004; revised 21 December 2004; accepted 6 January 2005
Available online 20 January 2005
Abstract—Rapid annulation employing an intramolecular Heck reaction yielded the functionalised 1,1,10-trimethyl-6-methoxy-
1,2,3,4-tetrahydroanthracene 4a, a key intermediate for the linear diterpenoid quinone umbrosone (1), and the related compounds
4b–d. A similar strategy was also successfully adopted for the synthesis of the 9-methyl tetrahydroanthracene ester 5 and the tetra-
hydrodibenzo[a,d]cycloheptene ester 6.
ꢀ 2005 Elsevier Ltd. All rights reserved.
The unusual rearranged linear abietane diterpenoid
o-quinone umbrosone (1), isolated from the roots of
Hyptis umbrosa Slazm (Lamiaceae) by Monache
et al.,1 shows significant activity against Gram-positive
bacteria.1 Several other new bioactive diterpenoid
anthraquinone derivatives such as aegyptinone A (2)
and aegyptinone B (3) were also isolated2 and character-
ised from a number of traditional medicinal plants. The
first total synthesis of umbrosone, reported by Ghosh
and Ghatak,3 utilised the key intermediate tetrahydro-
anthracene 4a and was carried out through a lengthy
sequence of classical reactions. The synthesis of
aegyptinones A and B was achieved by Danheiser
et al.4 in 1994, based upon a ꢀnew photochemical aro-
matic annulationꢁ. So far, three other multi-step formal
syntheses of 1 have been recorded involving skeletal
rearrangements of the ring-C-aromatic diterpenoids
(+)-dehyroabietic acid5a and (+)-podocarpic acid5b
as well as through a naphthalene derivative6 to the
established intermediate 4a.
cene analogues 4b–d. All these products, which incorpo-
rate the aryl core structure as well as the appropriate
methyl substituents of the natural anthraquinones, were
prepared by employing a highly efficient intramolecular
Heck reaction.7 A similar strategy has also been suc-
cessfully extended for the synthesis of the methyl tetra-
hydroanthracene 5 and the dibenzo[a,d]cycloheptene
Me
O
Me
O
O
O
Me
OH
Me
Me
Me
Me
O
Me
Me
Aegyptinone A 2
Umbrosone 1
Me
O
Me R1
OH
R2
Me
O
R3
4a: R1=R3=H; R2=OMe
Me
Me Me
Me
OH
Aegyptinone B 3
We describe herein a short and flexible convergent route
for the construction of 4a, the key intermediate3 for
umbrosone, and of a variety of other tetrahydroanthra-
4b: R1=R2=OMe; R3=H
4c: R1=OMe; R2=OBn; R3=H
4d: R1=R2=R3=OMe
OMe
OMe
OMe
Keywords: Heck reaction; Tetrahydroanthracene; Umbrosone; Suzuki
coupling; 7-endo Heck cyclisation; Benzocycloheptadiene.
OMe
MeO2C Me
MeO C Me
Me
5
2
*
Corresponding author. Tel.: +91 33 2473 3491; fax: +91 33 2473
5197; e-mail: ashisbanerjee@iicb.res.in
6
0040-4039/$ - see front matter ꢀ 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.01.021

1516
S. Sengupta et al. / Tetrahedron Letters 46 (2005) 1515–1519
CH2 R1
derivative 6 incorporating a gem-carboxymethyl–methyl
functionality.
HO
R2
i
ii
11
The desired vinyl alcohol substrates 11a–c for the intra-
molecular Heck reaction were derived from the methyl
ester analogue 78 of Hagemannꢁs ester. We initially con-
verted 7 to the 2-(o-bromobenzyl)cyclohexanones 10a9a
and 10b by adopting a modification of an established
route9a recently reported9b from this laboratory for
10c. The ketones 10a–c were then condensed with vinyl
lithium, generated in situ, to give only the corresponding
trans diastereoisomers 11a–c, as assigned by analogy,10
in excellent yields (Scheme 1).
H
Me
Me
12
CH2 R1
Me R1
R2
R2
iii
Me Me
13
Me Me
4
a: R1=H, R2=OMe; b: R1=R2=OMe;
c: R1=OMe, R2=OBn
For the intramolecular Heck reactions of 11a–c, we at-
tempted several literature procedures; the best results
were obtained by using Ma and Niꢁs method11
[Pd(OAc)2, K2CO3 and PPh3 in acetonitrile under reflux
for ca. 48 h]. The reactions proceeded exclusively in the
6-exo-mode, affording the respective crystalline tricyclic
alcohols 12a–c12 in excellent yields (Scheme 2). Reflux-
ing the alcohols 12a–c with p-TsOH in toluene gave mix-
tures of the corresponding dehydration products 13a–c
retaining the exo-methylene group, as deduced from
Scheme 2. Reagents and conditions: (i) Pd(OAc)2 (10 mol %), PPh3
(40 mol %), K2CO3 (6 equiv), CH3CN, reflux, 48 h, 12a (86%), 12b
(85%), 12c (84%); (ii) p-TsOH, toluene, reflux, 4 h; (iii) for 13a and 13b:
KOtBu (3 equiv), DMSO, rt, 72h, 4a (85%), 4b (88%); for 13c: KOtBu
(1 equiv), DMSO, rt, 3 h, 70%.
Finally, the trimethoxy derivative 4d could be smoothly
prepared from the dimethoxy anthracene 4b by selective
bromination with NBS in CH3CN followed by heating
the bromo derivative 14 with sodium methoxide in
methanol and DMF in the presence of CuI15 (Scheme 3).
1
the H NMR spectra. While 13a and 13b underwent
smooth aromatisation to the respective anthracenes 4a
and 4b in over 85% yields13 by treatment with an excess
of potassium tert-butoxide in DMSO14 at room temper-
ature for 72h, the O-benzyl analogue 13c gave a mixture
of the expected product 4c13 with significant amounts of
the debenzylated derivative. To our satisfaction, the
desired product 4c could be obtained pure in 70% yield
when the reaction was carried out under slightly altered
conditions using smaller amounts of potassium tert-
butoxide for a shorter period (Scheme 2).
In order to study the feasibility of the intramolecular
Heck reaction for the synthesis of functionalised tetra-
hydroanthracene derivatives carrying other substituents,
we decided to attempt it on substrates having gem-carb-
oxymethyl–methyl grouping. The 3-(o-bromobenzyl)-
cyclohexanone carboxylate ester 19 was considered as
a suitable substrate for this task (Scheme 4). Towards
this objective, ethyl 2-cyclohexanone carboxylate 15a
was treated with veratraldehyde in the presence of
DBU16 in refluxing MeOH to afford only the unsatu-
rated keto methyl ester 16 in moderate yield, obviously
arising through transesterification. Repeating the reac-
tion with methyl ester 15b gave 16 in marginally
improved yield. Methylation of 16 with MeI in the pres-
O
R1
R1
Br
R2
O
Br
+
R2
i
17
ence of K2CO3 led to the alkylated product 17, which
on catalytic hydrogenation gave the corresponding satu-
rated ketoester 18.
Me
MeO2C
CO2Me Br
Me
8
7
R1
R1
Br
Br
R2
R2
iii
O
O
Bromination of 18 with N-bromosuccinimide in acetoni-
trile afforded the bromoketoester 19 in very good yield.
ii
Me Me
R2
Me
10
9
Me OMe
R1
Me OMe
CH2
Br
HO
OMe
i
OMe
iv
4b
Me Me
ii
H
Me Me
14
Br
Me
Me
11
a: R1=H, R2=OMe; b: R1=R2=OMe;
c: R1=OMe, R2=OBn
Me OMe
OMe
Scheme 1. Reagents and conditions: (i) KOtBu, BuOH, NaI, reflux,
6 h, 8a (88%), 8b (86%), 8c (92%); (ii) LiOH, MeOH, H2O, rt, 24 h,
then H+, 9a (80%), 9b (70%), 9c (64%); (iii) Me2CuLi (3.5 equiv),
BF3ÆEt2O (4 equiv), ꢀ30 to 0 ꢁC, 10a (90%), 10b (87%), 10c (94%); (iv)
tri-n-butyl vinyl tin (3.7 equiv), MeLi (1.2M, 3.5 equiv), ꢀ78 ꢁC, 5 h,
11a (97%), 11b (84%), 11c (89%).
t
Me Me
OMe
4d
Scheme 3. Reagents and conditions: (i) NBS (1.1 equiv), CH3CN,
ꢀ20 ꢁC, 2h, 90%; (ii) NaOMe (5 equiv), CuI (3 equiv), DMF, MeOH,
reflux, 20 h, 60%.

S. Sengupta et al. / Tetrahedron Letters 46 (2005) 1515–1519
1517
H
H
OMe
OMe
OMe
i
ii
O
O
O
OMe
MeO2C Me
CO2R
CO2Me
15a: R=Et
15b: R=Me
16
17
iii
H
OMe
OMe
OMe
OMe
OMe
v
vi
O
OTf
OMe
OTf
Br
MeO2C Me
MeO2C Me
MeO2C Me
21
22
18
iv
vii
Br
H
H
OMe
OMe
OMe
OMe
OMe
OMe
viii
O
O
Br
MeO2C Me
H
MeO2C Me
MeO2C Me
24
19
23
X
ix
OMe
OMe
OMe
OMe
OH
Br
OTf
MeO2C Me
MeO2C Me
20
25
Scheme 4. Reagents and conditions: (i) veratraldehyde (1 equiv), DBU (1.1 equiv), MeOH, reflux, 48 h, (30% from 15a, 40% from 15b); (ii) MeI
(5 equiv), K2CO3 (5 equiv), acetone, reflux, 14 h, 82%; (iii) H2, Pd/C (10%), MeOH, 24 h, 95%; (iv) NBS (1.1 equiv), CH3CN, ꢀ30 ꢁC, 1.5 h, then rt,
24 h, 85%; (v) LDA (1.35 equiv), N-phenyltriflimide (1.2equiv), THF, ꢀ78 to 0 ꢁC, 6 h, then rt, 8 h, 60%; (vi) NBS (1.2equiv), CH 3CN, ꢀ30 ꢁC,
1.5 h, then rt, 24 h, 89%; (vii) PdCl2(CH3CN)2 (10 mol %), LiCl (5 equiv), tri-n-butylvinyltin (1.2equiv), DMF, rt, 24 h, 65%; (viii) Pd(PPh
)
3 4
(10 mol %), K2CO3 (1.2equiv), 2,4,6-trivinylcyclotriboroxane–pyridine complex (1.1 equiv), DME:H 2O (3:1), reflux, 24 h, 70%; (ix) LDA (1.5 equiv),
N-phenyltriflimide (1.4 equiv), THF, ꢀ78 to 0 ꢁC, 6 h, then rt, 8 h, 65%.
Unfortunately, attempted conversion of 19 to the
desired vinyl alcohol 20 employing various reaction
conditions failed. We therefore, modified the scheme
to prepare the bromodiene 23 or a styrenoid enol
triflate 25 to be used as substrates for the cyclisation.
OMe
OMe
i
23
25
MeO2C
Me
Me
OMe
OMe
5
The preparation of the target substrates 23 and 25 from
the common intermediate 18 is described in Scheme 4.
Treatment of 18 with LDA followed by N-phenyltri-
flimide18 furnished the enol triflate 21, which on bromina-
tion with N-bromosuccinimide in acetonitrile gave the
bromo triflate 22 in excellent yield. Selective olefination
of the enol triflate 22 with vinyl tin in the presence of
ii
+
5
MeO2C Me
6
Scheme 5. Reagents and conditions: (i) Pd(OAc)2 (10 mol %), PPh3
(40 mol %), K2CO3 (6 equiv), CH3CN, reflux, 48 h, 86%; (ii) (a)
Pd(OAc)2 (10 mol %), Bu4NH4Br (2equiv), NaOAc (6 equiv), DMF,
19
PdCl2(MeCN)2 produced the bromodiene 23 in good
80 ꢁC, 24 h, 5:6, 88:12(GLC); (b) Pd(OAc)
(1 mol %), DMA:DMF:Et3N, 7:1:1, 110 ꢁC, 30 min, 5:6, 43:57 (GLC).
(1 mol %), PPh3
2
yield.20 For the preparation of 25, the bromoaryl keto-
ester 19 was subjected to Suzuki coupling with 2,4,6-
trivinylcyclotriboroxane pyridine complex21 using tetra-
kis(triphenylphosphine) palladium(0) and K2CO3 in
DME/water 3:1 under reflux for 24 h to afford the styr-
ene 24 in good yield. The styrene 24 was transformed to
the corresponding enol triflate 2520 as before (Scheme 4).
excellent yield.22 The other substrate, the unstable styr-
enoid ester 25, gave intractable materials due to decom-
position under the same conditions. However, carrying
out the reaction under Jefferyꢁs conditions23 [using
Pd(OAc)2, Bu4NBr, NaOAc in DMF at 80 ꢁC], the 6-
exo and the rare 7-endo products 5 and 622 were ob-
tained from 25 in a ratio of 88:12(GLC). As functional-
ised 6-7-6 carbocyclic ring systems such as 6 form the
core structures of a number of rearranged diterpenoids
having potential bioactivity,24 we turned our attention
to the exploration of more selective 7-endo Heck
The intramolecular Heck reactions of 23 and 25 pro-
duced interesting results (Scheme 5). The cyclisation
studies were initially carried out with the relatively more
stable diene ester 23. With Pd(OAc)2, K2CO3 and PPh3
in refluxing acetonitrile11 under the conditions described
previously for the vinyl alcohols 11a–c, the bromo diene
23 furnished the fully aromatised 6-exo cyclic ester 5 in

1518
S. Sengupta et al. / Tetrahedron Letters 46 (2005) 1515–1519
References and notes
OMe
OMe
ii
25
1. Monache, F. D.; Monache, G. D.; Gacs-Baitz, E.;
De Coelho, J. S.; De Albuquerque, I. L.; De Chiappeta,
A.; De Mello, J. F. Phytochemistry 1990, 29, 3971–
3972.
MeO2C
Me
Me
5
OMe
OMe
2. Sabari, N. N.; Abou-Donia, A. A.; Ghazy, N. M.; Assad,
A. M.; El-Lakany, A. M.; Sanson, D. R.; Gracz, H.;
Barnes, C. L.; Schlemper, E. O.; Tempesta, M. S. J. Org.
Chem. 1989, 54, 4097–4099.
i
23
X
X
MeO C
Me
2
3. (a) Ghosh, K.; Ghatak, U. R. Tetrahedron Lett. 1994, 35,
5943–5944; (b) Ghosh, K.; Ghatak, U. R. J. Chem. Soc.,
Perkin Trans. 1 1999, 1359–1362.
4. Danheiser, R. L.; Casebier, D. S.; Huboux, A. H. J. Org.
Chem. 1994, 59, 4844–4848.
5. (a) Matsumoto, T.; Takeda, Y.; Usui, S.; Imai, S. Chem.
Pharm. Bull. 1996, 44, 530–533; (b) Rutledge, P. S.;
Rickard, C. E. F.; Liu, C. C.; Cambie, R. C. Aust. J.
Chem. 1998, 51, 605–610.
6. Manitto, P.; Monti, D.; Zanzola, S.; Speranza, G. J. Org.
Chem. 1997, 62, 6658–6665.
7. Link, J. T. Org. React. 2002, 60, 157–534.
8. Begbie, A. L.; Golding, B. T. J. Chem. Soc., Perkin Trans.
1 1972, 602–605.
9. (a) Pal, S.; Mukhopadhyaya, J. K.; Ghatak, U. R. J. Org.
Chem. 1994, 59, 2687–2694; (b) Banerjee, M.; Mukhopad-
hyay, R.; Achari, B.; Banerjee, A. Kr. Org. Lett. 2003, 5,
3931–3933.
10. Ghosh, A. K.; Ghosh, K.; Pal, S.; Ghatak, U. R. J. Chem.
Soc., Chem. Commun. 1993, 809–811; Ghosh, A. K.;
Ghosh, K.; Pal, S.; Ghatak, U. R. J. Chem. Soc., Chem.
Commun. 1993, 1176.
26
Scheme 6. Reagents and conditions: (i) tri-n-butylvinyltin (2equiv),
Pd(PPh3)4 (5 mol %), dioxane, reflux, 24 h, 90%; (ii) PdCl2(CH3CN)2
(10 mol %), LiCl (5 equiv), tri-n-butylvinyltin (1.2equiv), DMF, rt,
24 h, 80%.
cyclisation conditions, which has very little precedent.7
Amongst a number of variations studied, the best result
was realised by following a modification of the solvent
concentration of a recently recorded intermolecular
Heck coupling.25 Thus, treatment of 25 with Pd(OAc)2
and PPh3 in DMA-DMF at 110 ꢁC in the presence
of Et3N as base produced a mixture of the 6-exo-
and the 7-endo products 5 and 6 in a ratio of 43:57
(GLC). In contrast, the diene ester 23 was mostly recov-
ered unchanged when subjected to the same reaction
conditions.
For a more direct synthetic entry to the desired 6-7-6 tri-
cyclic compound 6 as the exclusive or major product
through ring closing metathesis (RCM),26 we focussed
our interest on the preparation of the divinyl ester 26
(Scheme 6). Interestingly, an attempted Echaverren
and Stille27 vinylation reaction of 23 in the presence of
Pd(PPh3)4 and tributyl vinyl tin in refluxing dioxane
for 24 h, furnished only the Heck cyclisation product
5, while under the same reaction conditions 25 remained
unreacted. Attempted vinylation of styrenoid enol-tri-
flate 25, under the conditions successfully applied19 for
the conversion of 22 to 23 (cf. Scheme 4), surprisingly
led to the tetrahydroanthracene 5 in 80% yield as the
sole isolable product.
11. Ma, S.; Ni, B. J. Org. Chem. 2002, 67, 8280–8283.
12. Spectral data for the new compounds: 12a: mp 112 ꢁC; 1H
NMR (300 MHz, CDCl3): d 0.96 (3H, s), 1.12 (3H, s), 1.22–
1.31 (1H, m), 1.48–1.63 (4H, m), 1.67–1.77 (1H, m), 1.86–
1.99 (1H, m), 2.11–2.16 (1H, m), 2.78 (1H, dd, J 5.2,
16.5 Hz), 2.93 (1H, dd, J 12.2, 16.4 Hz), 3.81 (3H, s), 5.28
(1H, s), 5.49 (1H, s), 6.82(1H, dd, J 2.6, 8.4 Hz), 7.06–7.09
(2H, m); 13C NMR (75 MHz, CDCl3): d 18.19 (CH2), 22.17
(CH3), 25.72 (CH2), 31.70 (CH3), 33.36 (C), 36.58 (CH2),
42.01 (CH2), 48.44 (CH), 55.13 (CH3), 71.06 (C), 107.35
(CH2), 109.59 (CH), 114.31 (CH), 129.02 (C), 129.63 (CH),
133.83 (C), 150.87 (C), 157.69 (C); EIMS: m/z: 272 (M+).
Anal. Calcd for C18H24O2: C, 79.37%, H, 8.88%. Found C,
1
79.51%, H, 8.97%. Compound 12b: mp 90 ꢁC; H NMR
(300 MHz, CDCl3): d 0.94 (3H, s), 1.11 (3H, s), 1.14 (1H, br
s), 1.21–1.31 (2H, m), 1.49–1.63 (2H, m), 1.72–1.82 (1H,
m), 1.87–1.97 (1H, m), 2.01–2.08 (1H, m), 2.77–2.94 (2H,
m), 3.69 (3H, s), 3.85 (3H, s), 5.54 (1H, s), 6.08 (1H, s), 6.81
(1H, d, J 8.4 Hz), 6.88 (1H, d, J 8.4 Hz); 13C NMR
(75 MHz, CDCl3): d 18.20 (CH2), 21.83 (CH3), 26.33
(CH2), 31.49 (CH3), 33.43 (C), 36.24 (CH2), 41.93 (CH2),
48.53 (CH), 55.84 (CH3), 59.64 (CH3), 71.91 (C), 111.67
(CH), 112.64 (CH2), 123.59 (CH), 127.53 (C), 130.52 (C),
147.24 (C), 147.79 (C), 151.07 (C); EIMS: m/z: 302(M +).
Anal. Calcd for C19H26O3: C, 75.46%, H, 8.67%. Found C,
In summary, a rapid generalised synthesis of substituted
tetrahydroanthracene core structures, including the
advanced intermediate 4a for the diterpenoid quinone
umbrosone 1, constituting a formal total synthesis of
1, has been achieved employing an intramolecular Heck
reaction as the key step. Heck reaction of the styrenoid
enol triflate ester 24 producing the rare 7-endo-product 6
could be of interest in the synthesis of dibenzo-
[a,d]cycloheptenes as potential intermediates towards
the related bioactive 9(10 ! 20)-abeo-abieta-8,11,13-
triene diterpenoids.
1
75.31%, H, 8.59%. Compound 12c: mp 88 ꢁC; H NMR
(300 MHz, CDCl3): d 0.93 (3H, s), 1.10 (3H, s), 1.16 (1H, br
s), 1.17—1.30 (2H, m), 1.49–1.64 (2H, m), 1.73–1.82 (1H,
m), 1.91–2.01 (1H, m), 2.04–2.08 (1H, m), 2.79–2.94 (2H,
m), 3.74 (3H, s), 5.08, 5.14 (2H, 2 · d, J 12.0 Hz), 5.54 (1H,
s), 6.09 (1H, s), 6.83 (2H, s), 7.26–7.46 (5H, m); 13C NMR
(75 MHz, CDCl3): d 18.39 (CH2), 21.99 (CH3), 26.59
(CH2), 31.66 (CH3), 33.66 (C), 36.45 (CH2), 42.10 (CH2),
Acknowledgements
We are grateful to Professor U. R. Ghatak of our insti-
tute for his excellent suggestions and criticisms, and to
UGC (New Delhi) and Dabur Research Foundation
(U.P.) for the research fellowship to S.S.
48.68 (CH), 60.02(CH ), 71.22 (CH2), 72.22 (C), 112.91
3
(CH2), 114.26 (CH), 123.79 (CH), 127.27 (2 · CH), 127.78
(CH), 127.90 (C), 128.50 (2 · CH), 131.34 (C), 137.41 (C),
147.41 (C), 148.72(C), 150.43 (C); EIMS: m/z: 378 (M+).

S. Sengupta et al. / Tetrahedron Letters 46 (2005) 1515–1519
1519
Anal. Calcd for C25H30O3: C, 79.33%, H, 7.99%. Found C,
79.58%, H, 7.83%.
13. Spectral data for the new compounds: 4a: mp 110 ꢁC; H
(3H, s), 3.83 (3H, s), 3.85 (3H, s), 4.97–5.10 (2H, m), 6.36
(1H, dd, J 12and 18 Hz), 6.74 (1H, s), 7.02(1H, s); 13C
NMR (75 MHz, CDCl3): d 18.74 (CH2), 23.89 (CH3),
30.34 (CH2), 36.33 (CH2), 39.19 (CH2), 45.92(C), 51.87
(CH3), 55.85 (CH3), 56.09 (CH3), 111.93 (CH), 114.61 (C),
115.29 (CH), 115.77 (CH2), 131.14 (C), 133.63 (CH),
134.91 (C), 135.22(C), 147.67 (C), 148.43 (C), 177.92(C);
EIMS: m/z: 410 (M+ for Br81), 408 (M+ for Br79). Anal.
Calcd for C20H25BrO4: C, 58.69%, H, 6.16%. Found C,
58.48%, H, 6.25%. Compound 25: 1H NMR (300 MHz,
CDCl3): d 1.48 (3H, s), 1.58–1.66 (2H, m), 1.80–1.99 (2H,
m), 2.03–2.12 (2H, m), 3.50 (1H, d, J 15 Hz), 3.72(1H, d, J
15 Hz), 3.75 (3H, s), 3.88 (3H, s), 3.90 (3H, s), 5.22 (1H, d,
J 11 Hz), 5.53 (1H, d, J 17 Hz), 6.69 (1H, s), 6.80 (1H, dd,
J 11 and 17 Hz), 6.99 (1H, s); 13C NMR (75 MHz,
1
NMR (300 MHz, CDCl3): d 1.38 (6H, s), 1.68–1.72(2H,
m), 1.87–1.93 (2H, m), 2.51 (3H, s), 2.90 (2H, t, J 6.5 Hz),
3.93 (3H, s), 7.06 (1H, dd, J 2.3, 8.9 Hz), 7.23 (1H, d, J
2.0 Hz), 7.65 (1H, s and 1H, d, J 8.8 Hz); 13C NMR
(75 MHz, CDCl3): d 14.44 (CH3), 19.73 (CH2), 29.05
(CH2), 32.51 (2 · CH3), 34.23 (C), 38.77 (CH2), 55.22
(CH3), 102.18 (CH), 117.02 (CH), 123.25 (CH), 127.63
(C), 129.46 (C), 129.65 (CH), 131.69 (C), 133.39 (C),
142.38 (C), 157.16 (C); EIMS: m/z: 254 (M+). Anal. Calcd
for C18H22O: C, 84.99%, H, 8.72%. Found C, 84.72%, H,
8.84%. Compound 4b: mp 99 ꢁC; 1H NMR (300 MHz,
CDCl3): d 1.38 (6H, s), 1.67–1.71 (2H, m), 1.86–1.92 (2H,
m), 2.81 (3H, s), 2.82–2.88 (2H, m), 3.83 (3H, s), 3.96 (3H,
s), 7.19 (1H, d, J 8.9 Hz), 7.49 (1H, d, J 8.9 Hz), 7.61 (1H,
s); 13C NMR (75 MHz, CDCl3): d 16.64 (CH3), 19.78
(CH2), 29.19 (CH2), 32.40 (2 · CH3), 34.13 (C), 38.56
(CH2), 56.90 (CH3), 60.86 (CH3), 113.93 (CH), 123.62
(CH), 124.71 (CH), 126.45 (C), 129.59 (C), 130.14 (C),
134.70 (C), 142.72 (CH), 144.87 (C), 149.37 (C); EIMS:
m/z: 284 (M+). Anal. Calcd for C19H24O2: C, 80.24%, H,
8.51%. Found C, 80.54%, H, 8.35%. Compound 4c: mp
CDCl3): d 18.32(CH ), 22.14 (CH3), 28.71 (CH2), 33.57
2
(CH2), 37.33 (CH2), 47.67 (C), 52.29 (CH3), 55.74 (CH3),
55.77 (CH3), 108.45 (CH), 112.09 (CH), 112.89 (CH2),
126.88 (C), 129.30 (C), 129.49 (C), 132.22 (C), 133.61
(CH), 143.13 (C), 147.83 (C), 148.68 (C), 174.15 (C);
EIMS: m/z: 478 (M+). Anal. Calcd for C21H25F3O7S: C,
52.71%, H, 5.27%. Found C, 52.96%, H, 5.40%.
21. Kernis, F.; O’Shea, D. F. J. Org. Chem. 2002, 67, 4968–
4971.
1
1
92 ꢁC; H NMR (300 MHz, CDCl3): d 1.37 (6H, s), 1.67–
22. Spectral data for the new compounds: 5: mp 130 ꢁC; H
1.70 (2H, m), 1.86–1.92 (2H, m), 2.83 (3H, s), 2.83–2.88
(2H, m), 3.88 (3H, s), 5.22 (2H, s), 7.18 (1H, d, J 8.9 Hz),
7.31–7.51 (6H, m), 7.61 (1H, s); 13C NMR (75 MHz,
CDCl3): d 16.76 (CH3), 19.84 (CH2), 29.25 (CH2), 32.47
(2 · CH3), 34.23 (C), 38.61 (CH2), 61.06 (CH3), 72.30
(CH2), 116.44 (CH), 123.70 (CH), 124.69 (CH), 126.64
(C), 127.46 (2 · CH), 127.77 (CH), 128.47 (2 · CH),
130.08 (C), 130.46 (C), 134.79 (C), 137.68 (C), 143.11
(C), 146.06 (C), 148.61 (C); EIMS: m/z: 360 (M+). Anal.
Calcd for C25H28O2: C, 83.29%, H, 7.83%. Found C,
NMR (300 MHz, CDCl3): d 1.62(3H, s), 1.88–1.99 (3H,
m), 2.07–2.11 (1H, m), 2.42 (3H, s), 2.98–3.00 (2H, m),
3.68 (3H, s), 3.97 (3H, s), 3.99 (3H, s), 6.99 (1H, s), 7.17
(1H, s), 7.35 (1H, s); 13C NMR (75 MHz, CDCl3): d 16.26
(CH3), 19.15 (CH2), 25.73 (CH3), 31.60 (CH2), 38.79
(CH2), 47.02 (C), 52.27 (CH3), 55.76 (CH3), 55.78 (CH3),
102.95 (CH), 105.90 (CH), 125.07 (CH), 127.74 (C), 127.96
(C), 130.30 (C), 132.76 (C), 134.61 (C), 148.92 (C), 149.22
+
(C), 180.20 (C); EIMS: m/z: 32 8 (M). Anal. Calcd for
C20H24O4: C, 73.15%, H, 7.37%. Found C, 73.43%, H,
7.27%. Compound 6: mp 138 ꢁC; 1H NMR (300 MHz,
CDCl3): d 1.24 (3H, s), 1.42–1.71 (3H, m), 1.97–2.02 (1H,
m), 2.34–2.43 (2H, m), 2.90 (2H, s), 3.68 (3H, s), 3.87 (3H,
s), 3.90 (3H, s), 6.24 (1H, d, J 12Hz), 6.63 (1H, s), 6.79
(1H, s), 6.88 (1H, d, J 12Hz); 13C NMR (75 MHz,
CDCl3): d 19.20 (CH2), 24.84 (CH3), 31.53 (CH2), 34.79
1
83.07%, H, 7.98%. Compound 4d: mp 146 ꢁC; H NMR
(300 MHz, CDCl3): d 1.39 (6H, s), 1.66–1.70 (2H, m),
1.86–1.94 (2H, m), 2.79 (3H, s), 2.82–2.86 (2H, m), 3.76
(3H, s), 3.97 (6H, s), 6.57 (1H, s), 8.09 (1H, s); 13C NMR
(75 MHz, CDCl3): d 16.60 (CH3), 19.83 (CH2), 29.23
(CH2), 32.61 (2 · CH3), 34.44 (C), 38.73 (CH2), 55.68
(CH3), 57.58 (CH3), 61.02(CH 3), 94.67 (CH), 117.17
(CH), 121.28 (C), 126.68 (C), 130.11 (C), 135.54 (C).
139.09 (C), 142.32 (C), 149.05 (C), 152.08 (C); EIMS: m/z:
314 (M+). Anal. Calcd for C20H26O3: C, 76.40%, H,
8.33%. Found C, 76.11%, H, 8.49%.
(CH2), 40.66 (CH2), 46.18 (C), 51.92(CH ), 55.89 (CH3),
3
55.95 (CH3), 109.89 (CH), 110.45 (CH), 128.49 (C), 128.98
(CH), 129.60 (C), 130.16 (C), 131.10 (CH), 133.33 (C),
146.94 (C), 149.55 (C), 177.90 (C); EIMS: m/z: 32 8 (M ).
+
Anal. Calcd for C20H24O4: C, 73.15%, H, 7.37%. Found
C, 73.32%, H, 7.29%.
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20. Spectral data for the new compounds: 23: 1H NMR
(300 MHz, CDCl3): d 1.45 (3H, s), 1.65–1.70 (3H, m),
1.99–2.16 (3H, m), 3.49, 3.59 (2H, 2 · d, J 16 Hz), 3.67