A short enantioselective synthesis of (+)-eleutherin, (+)-allo-eleutherin and a formal synthesis of (+)-nocardione B

Article abstract of DOI:10.1016/j.tetlet.2008.08.065

A short enantioselective synthesis of (+)-eleutherin, (+)-allo-eleutherin and the formal synthesis of (+)-nocardione B is described. The synthesis is completed in six steps in overall yields of 8% for eleutherin and 14% for allo-eleutherin. The synthetic strategy features an efficient combination of the D?tz annulation reaction with a chiral alkyne and an oxa-Pictet Spengler reaction as the keys steps in the stereodivergent synthesis of (+)-eleutherin and (+)-allo-eleutherin. The synthesis of (S)-(+)-2-(2′-hydroxypropyl)-5-methoxy-1,4-naphthoquinone entails the formal synthesis of (+)-nocardione B.

Full text of DOI:10.1016/j.tetlet.2008.08.065

Tetrahedron Letters 49 (2008) 6341–6343
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A short enantioselective synthesis of (+)-eleutherin, (+)-allo-eleutherin
and a formal synthesis of (+)-nocardione B
*
Rodney A. Fernandes , Vijay P. Chavan, Arun B. Ingle
Department of Chemistry, Indian Institute of Technology Bombay, Powai, Mumbai 400 076, Maharashtra, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A short enantioselective synthesis of (+)-eleutherin, (+)-allo-eleutherin and the formal synthesis of (+)-
nocardione B is described. The synthesis is completed in six steps in overall yields of 8% for eleutherin
and 14% for allo-eleutherin. The synthetic strategy features an efficient combination of the Dötz
annulation reaction with a chiral alkyne and an oxa-Pictet Spengler reaction as the keys steps in the
stereodivergent synthesis of (+)-eleutherin and (+)-allo-eleutherin. The synthesis of (S)-(+)-2-(20-
hydroxypropyl)-5-methoxy-1,4-naphthoquinone entails the formal synthesis of (+)-nocardione B.
Ó 2008 Elsevier Ltd. All rights reserved.
Received 15 July 2008
Revised 14 August 2008
Accepted 20 August 2008
Available online 23 August 2008
Keywords:
Asymmetric synthesis
Eleutherins
Nocardiones
Dötz annulation
Oxa-Pictet Spengler reaction
Eleutherin 1 was isolated from the bulbs of Eleutherin bulbosa1
in 1950 and shortly after, the C-3 epimer, isoeleutherin 22 was also
isolated from the same bulb extracts (Fig. 1). Eleutherin 1 is shown
to exhibit activity3 against Bacillus subtilis. Extracts of Eleutherin
americana of which eleutherin and isoeleutherin are the major con-
stituents have been used to treat the heart disease angina pecto-
ris.4 Also, (+)-eleutherin is a reversible inhibitor of topoisomerase
II—a target for anticancer agents.5 (+)-Allo-eleutherin 3 (Fig. 1) is
an enantiomer of isoeleutherin 2 and was produced when (+)-ele-
utherin 1 was treated with phosphoric acid.2 In 2000, Otani et al.
isolated (ꢀ)-nocardione A 4 and (ꢀ)-nocardione B ent-5 as new
tyrosine phosphate inhibitors.6 These also possess moderate anti-
fungal and cytotoxic activities.6
Eleutherin and isoeleutherin have been the targets of extensive
synthetic studies; however, mostly in racemic form.7 There are
only two recent enantioselective syntheses8 of (+)-eleutherin 1,
while (ꢀ)-isoeleutherin 2 or its enantiomer (+)-allo-eleutherin 32
has not yet been synthesized in enantiopure form. The first enan-
tioselective synthesis of 1 involved the synthesis of (S)-mellein9
in several steps and then its conversion in a five-step sequence
to eleutherin.8a The second synthesis by Brimble and co-workers8b
based on the well-known Hauser–Kraus annulation10 involves
eight steps leading to a 5.5% overall yield.
Nocardiones 4 and 5 were first synthesized by Tanada and
Mori,11 and their absolute configuration was also determined.
Racemic syntheses of nocardiones are also known.12 A radical
cyclization strategy has been used recently in the synthesis of
(+)-norcardione A ent-4.13
In continuation of our efforts on the enantioselective synthesis
of natural products,14 we recently employed the Dötz annulation
reaction and asymmetric dihydroxylation in the highly enantiose-
lective synthesis of (ꢀ)-juglomycin A and its non-natural enantio-
mer.14c Herein, we report a short and stereodivergent synthesis of
both (+)-eleutherin 1 and (+)-allo-eleutherin 3. The synthetic strat-
egy (Scheme 1) features a Dötz annulation reaction with the chiral
alkyne 6 (to install the naphthalene 8) and an oxa-Pictet Spengler
reaction (to give the pyran ring compound 9) as the key steps in
the stereodivergent synthesis of both 1 and the first enantioselec-
tive synthesis of 3. Compound 8 is an intermediate in the synthesis
of (+)-nocardione B 5.
O
OMe
O
O
OMe
OMe
O
O
O
O
O
O
1
2
3
O
O
OH
O
O
OMe
O
O
4
5
Figure 1. (+)-Eleutherin 1, (ꢀ)-isoeleutherin 2, (+)-allo-eleutherin 3, (ꢀ)-nocardi-
one A 4 and (+)-nocardione B 5.
* Corresponding author. Tel.: +91 22 25767174; fax: +91 22 25767152.
E-mail address: rfernand@chem.iitb.ac.in (R. A. Fernandes).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.08.065

6342
R. A. Fernandes et al. / Tetrahedron Letters 49 (2008) 6341–6343
Dötz annulation
OMe
OMe
OH
OMe
Cr(CO)5
OMe
7
OMe
oxa-Pictet
Spengler
Br
O
O
OMe
OMe
ii
OMe
OMe
OMe
i
OTBDMS
O
O
O
13
14
O
O
OMe
OMe
9
3
(+)-allo-eleutherin
OMe
OMe
1
(+)-eleutherin
iii
iv
OH
O
×
O
OMe
6
O
OMe
OMe
OTBDMS
+
8
OH
iv
15
OH
OH
OMe
OMe
OMe
O
7
O
O
OMe
OMe
Cr(CO)5
8
OH
5 (+)-nocardione B
v
ref. 11
(+)-nocardione B
OH
Scheme 1. Synthetic strategy to (+)-1, (+)-3 and (+)-5.
5
O
16
O
17
EtO
H
EtO
i
ii
Scheme 3. Dötz annulation and oxa-Pictet Spengler reactions. Reagents and
conditions: (i) n-BuLi (1.04 equiv), THF, ꢀ78 °C, 5 min, Cr(CO)6 (1.0 equiv), ꢀ78 °C
to 0 °C, 3 h, then Me3OBF4 (1.5 equiv), CH2Cl2, 0 °C to rt, 3 h, 83%;14c (ii)
6
O
O
OH
OTBDMS
10
11
(1.5 equiv), THF, 45 °C, 12 h, 69%; (iii) TBAF (1.2 equiv), THF, rt, 2 h, 91%; (iv)
(CH3O)2CHCH3 (2.0 equiv), BF3ꢁOEt2 (3.0 equiv), Et2O/THF (4:1), rt, 12 h, 93%; (v)
(NH4)2Ce(NO3)6 (2.0 equiv), MeCN/H2O (1:1), rt, 1 h, 83%.
iii
O
OTBDMS
OTBDMS
6
12
OMe
OMe
OMe
OMe
OMe
Scheme 2. Synthesis of chiral alkyne 6. Reagents and conditions: (i) TBDMSCl
(1.3 equiv), imidazole (2.5 equiv), CH2Cl2, rt, 12 h, quant.; (ii) DIBAL-H (1.1 equiv),
CH2Cl2, ꢀ78 °C, 2 h; (iii) (a) CBr4 (2.0 equiv), PPh3 (4.0 equiv), CH2Cl2, 0 °C, 3.5 h; (b)
n-BuLi (2.1 equiv), THF, ꢀ78 °C, 2 h, 82% over two steps.
OTBDMS
OTBDMS
i
14
OH
18
ii
The chiral alkyne 6 required for the Dötz annulation reaction
was easily prepared as shown in Scheme 2. Commercially available
ethyl (S)-3-hydroxybutyrate 10 on hydroxyl protection as the
TBDMS ether afforded 11 in quantitative yield. DIBAL-H reduction
of the ester group gave aldehyde 12, and Corey–Fuchs15 alkyne for-
mation gave the desired chiral alkyne 6 in 82% yield (over two
steps).
OMe
OMe
OMe
OMe
OMe
O
iii
OH
OMe
9a
19
OMe
OMe
The Fischer carbene complex 7 was prepared as reported ear-
lier14c (from 2-bromoanisole 13) and condensed with the chiral
alkyne 6 (1.5 equiv) via the Dötz annulation reaction16 to afford
the substituted naphthalene 14 in a good yield of 69% (Scheme 3).
Deprotection of the TBDMS group gave the alcohol 8 in 91% yield.
We planned to install the pyran ring through oxa-Pictet Spengler
reaction17 to prepare 15. It is known in the literature that pyran
ring formation on similar substrates with acetaldehyde under
acidic conditions gives a variable mixture of cis- and trans-1,3-iso-
mers depending on the reaction conditions.7a,18 Towards this end,
when we subjected the alcohol 8 to the oxa-Pictet Spengler reac-
tion with acetaldehyde dimethylacetal and BF3ꢁOEt2, the seven-
membered cyclic acetal 16 was obtained in 93% yield instead of
15. This is different from the pyran ring formation of similar hydro-
quinone compounds when treated with acetaldehyde under acidic
conditions.18 Compound 16 gave four aryl-H signals in its 1H NMR
spectrum including a singlet at d 6.56 ppm corresponding to the
naphthalene C-2 proton,19 where the pyranylation could have
occurred. We further confirmed the formation of 16 by treating it
with cerium(IV) ammonium nitrate (CAN) to produce the quinone
17 in 83% yield. The quinone 17 is a useful intermediate in the syn-
thesis of (+)-nocardione B as reported earlier.11 Hence, this entails
a formal synthesis of (+)-5.
O
iv
9b OMe
iv
O
O
OMe
O
OMe
O
O
O
1 (+)-eleutherin
3 (+)-allo-eleutherin
Scheme 4. Synthesis of 1 and 3. Reagents and conditions: (i) NaH (3.0 equiv), MeI
(3.1 equiv), DMF, 0 °C to rt, 2 h, 85%; (ii) TBAF (1.2 equiv), THF, rt, 2 h, 95%; (iii) see
Table 1;21 (iv) (NH4)2Ce(NO3)6 (2.0 equiv), MeCN/H2O (1:1), rt, 1 h, 86% for 1 and
89% for 3.
TBDMS group gave the alcohol 19 in 95% yield. The oxa-Pictet
Spengler reaction of 19 with acetaldehyde dimethylacetal and
BF3ꢁOEt2 at room temperature for 14 h (Table 1, entry 1) gave a
mixture of 9a:9b in a 32:68 ratio and 92% yield.20 We envisaged
that the reaction over shorter time through kinetic control would
produce the cis-isomer as the major product. However, when the
reaction was carried out for 1 h at room temperature it resulted
in only a marginal difference of the ratio of 9a:9b = 36:64 (Table
1, entry 2) and an 84% yield. The reaction was also carried out at
0 °C which was rather slow and after 2 h gave 9a:9b in a 43:57
ratio and 78% yield (Table 1, entry 3).
Since pyranylation on 8 was not possible in the presence of the
phenolic hydroxyl group, it became necessary to protect it before
the pyranylation reaction. Phenol 14 was therefore converted into
its methyl ether 18 in 85% yield (Scheme 4). Deprotection of the

R. A. Fernandes et al. / Tetrahedron Letters 49 (2008) 6341–6343
6343
Table 1
Oxa-Pictet Spengler reaction on 19 to give 9a and 9b
Entry
Reaction conditions
% Yield
9a:9b
1
2
3
(CH3O)2CHCH3 (2.0 equiv), BF3ꢁOEt2 (3.0 equiv), THF/Et2O (1:4), rt, 14 h
(CH3O)2CHCH3 (2.0 equiv), BF3ꢁOEt2 (3.0 equiv), THF/Et2O (1:4), rt, 1 h
(CH3O)2CHCH3 (2.0 equiv), BF3ꢁOEt2 (3.0 equiv), THF/Et2O (1:4), 0 °C, 2 h
92
84
78
32:68
36:64
43:57
The mixture of 9a:9b was easily separated by preparative TLC21
11. Tanada, Y.; Mori, K. Eur. J. Org. Chem. 2001, 4313.
12. Yang, H.; Lu, W.; Bao, J. X.; Aisa, H. A.; Cai, J. C. Chin. Chem. Lett. 2001, 12, 883.
13. (a) Clive, D. L. J.; Fletcher, S. P. Chem. Commun. 2003, 2464; (b) Clive, D. L. J.;
Fletcher, S. P.; Liu, D. J. Org. Chem. 2004, 69, 3282.
14. (a) Fernandes, R. A. Eur. J. Org. Chem. 2007, 5064; (b) Fernandes, R. A.
Tetrahedron: Asymmetry 2008, 19, 15; (c) Fernandes, R. A.; Chavan, V. P.
Tetrahedron Lett. 2008, 49, 3899.
15. Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, 36, 3769.
16. (a) Dötz, K. H. Angew. Chem., Int. Ed. Engl. 1975, 14, 644; (b) Dötz, K. H.;
Tomuschat, P. Chem. Soc. Rev. 1999, 28, 187.
17. For oxa-Pictet Spengler reactions see: (a) Pyrek, J. S.; Achmatowicz, O., Jr.;
Zamojski, A. Tetrahedron 1977, 33, 673; (b) DeNinno, M. P.; Schoenleber, R.;
Perner, R. J.; Lijewski, L.; Asin, K. E.; Britton, D. R.; MacKenzie, R.; Kebabian, J.
W. J. Med. Chem. 1991, 34, 2561; (c) DeNinno, M. P.; Perner, R. J.; Morton, H. E.;
DiDomenico, S., Jr. J. Org. Chem. 1992, 57, 7115; (d) Masquelin, T.; Hengartner,
U.; Streith, J. Synthesis 1995, 780; (e) Masquelin, T.; Hengartner, U.; Streith, J.
Helv. Chim. Acta 1997, 80, 43; (f) Giles, G. F.; Rickards, R. W.; Senanayake, B. S. J.
Chem. Soc., Perkin Trans. 1 1998, 3949; (g) Contant, P.; Haess, M.; Riegl, J.;
Scalone, M.; Visnick, M. Synthesis 1999, 821; (h) Bianchi, D. A.; Rua, F.;
Kaufman, T. S. Tetrahedron Lett. 2004, 45, 411.
to give 9a22 (30%) and 9b23 (51%) from 19. Oxidation of 9a with
CAN produced (+)-eleutherin 1 {½a D25
ꢂ
+338 (c 0.25, CHCl3); natural
(+)-eleutherin 1 ½a D25
ꢂ
+346 (c 1.01, CHCl3)1} in 86% yield. Similarly,
oxidation of 9b with CAN gave (+)-allo-eleutherin 3 {½a D25
ꢂ
+65.6
(c 0.3, CHCl3), lit.2a
spectroscopic and analytical data of 1 were in full agreement with
those reported.8 (+)-Allo-eleutherin 3 was fully characterized by
spectroscopic and analytical methods.24
½
a 2D5
+45 (c 1.075, CHCl3)} in 89% yield. The
ꢂ
In summary, a short enantioselective synthesis of both (+)-ele-
utherin (8% overall yield) and (+)-allo-eleutherin (14% overall
yield) has been achieved in six steps (for both). The synthetic strat-
egy features an efficient combination of a Dötz annulation reaction
with a chiral alkyne and the oxa-Pictet Spengler reaction as the key
steps in the stereodivergent synthesis of both (+)-eleutherin and
the first enantioselective synthesis of (+)-allo-eleutherin. Since
(+)-allo-eleutherin is an enantiomer of (ꢀ)-(1R,3R)-isoeleutherin
2,8 it should have the (1S,3S) configuration. The synthesis of
(S)-(+)-2-(20-hydroxypropyl)-5-methoxy-1,4-naphthoquinone 17
entails the formal synthesis of (+)-nocardione B 5.11 Application
of this strategy to the synthesis of other related pyranonaphtho-
quinone natural products is in progress.
18. (a) Cameron, D. W.; Feutrill, G. I.; Pietersz, G. A. Aust. J. Chem. 1982, 35,
1481; (b) Pyrek, J., St.; Achmatowicz, O., Jr.; Zamojski, A. Tetrahedron 1977,
33, 673; (c) Li, T.; Ellison, R. H. J. Am. Chem. Soc. 1978, 100, 6263; (d)
Kometani, T.; Takeuchi, Y.; Yoshii, E. J. Org. Chem. 1983, 48, 2630; (e) Yoshii,
E.; Kometani, T.; Nomura, K.; Takeuchi, Y.; Odake, S.; Nagata, Y. Chem. Pharm.
Bull. 1984, 32, 4779; (f) Naruta, Y.; Uno, H.; Maruyama, K. Chem. Lett. 1982,
609.
19. Data for 16: Pale yellow solid; mp 143–144 °C; ½a D25
ꢀ71.5 (c 0.34, CHCl3); IR
ꢂ
(CHCl3):
m = 3138, 2968, 2928, 2835, 1627, 1603, 1509, 1463, 1388, 1333, 1284,
1250, 1115, 1072, 1045, 977, 927, 894, 863, 842, 761 cmꢀ1 1H NMR (400 MHz,
;
CDCl3/TMS): d 1.40 (d, 3H, J = 6.0 Hz, CHCH3), 1.69 (d, 3H, J = 5.2 Hz, CHCH3),
3.33 (m, 2H, CH2-Ar), 3.76 (m, 1H, CH2CHCH3), 3.94 (s, 3H, OCH3), 3.97 (s, 3H,
OCH3), 4.84 (q, 1H, J = 5.2 Hz, CHCH3), 6.56 (s, 1H, H-Ar), 6.85 (d, 1H, J = 7.7 Hz,
H-Ar), 7.40 (dd, 1H, J = 8.4, 8.0 Hz, H-Ar), 7.74 (d, 1H, J = 8.0 Hz, H-Ar); 13C NMR
(100 MHz, CDCl3/CHCl3): d 22.51 (CHCH3), 22.76 (CHCH3), 44.36 (CH2), 56.59
(OCH3), 57.22 (OCH3), 74.68 (CH), 103.50 (OOCHCH3), 106.34 (Ar), 109.32 (Ar),
114.88 (Ar), 116.2 (Ar), 126.61 (Ar), 127.15 (Ar), 131.43 (Ar), 148.15 (Ar),
152.83 (Ar), 157.09 (Ar); MS (I): m/e = 288 [M+] (100); Calcd for C17H20O4
(288.34): C, 70.81, H, 6.99. Found: C, 70.77; H, 7.28.
Acknowledgements
The authors are indebted to IRCC and the Department of Chem-
istry, IIT-Bombay, for financial support. The INSA Young Scientist
start-up support grant by INSA, New Delhi, is also acknowledged.
V.P.C. and A.B.I. are grateful to CSIR, New Delhi, for research
fellowships.
20. The diastereomer ratio was determined by 1H NMR.
21. All the mixtures in entries 1–3, Table 1, were mixed to give an average
9a:9b = 37:63 mixture and 85% yield. This on separation by preparative thin
layer chromatography (PTLC) gave 9a in 30% yield and 9b in 51% yield from 19.
These yields were taken into account while calculating the overall yield.
22. The spectroscopic and analytical data of 9a were in full agreement with those
reported.8b
References and notes
1. (a) Schmid, H.; Meijer, T. M.; Ebnöther, A. Helv. Chim. Acta 1950, 33, 595; (b)
Schmid, H.; Ebnöther, A.; Meijer, T. M. Helv. Chim. Acta 1950, 33, 1751.
2. For isolation see: (a) Schmid, H.; Ebnöther, A. Helv. Chim. Acta 1951, 34, 561. For
configuration see: (b) Schmid, H.; Ebnöther, A. Helv. Chim. Acta 1951, 34, 1041.
3. Bianchi, C.; Ceriotti, G. J. Pharm. Sci. 1975, 64, 1305.
4. (a) Chen, Z.; Huang, H.; Wang, C.; Li, Y.; Ding, J. Zhongcaoyao 1981, 12, 484; (b)
Ding, J.; Huang, H. Zhongcaoyao 1982, 13, 499.
5. Krishnan, P.; Bastow, K. F. Biochem. Pharmacol. 2000, 60, 1367.
6. Otani, T.; Sugimoto, Y.; Aoyagi, Y.; Igarashi, Y.; Furumai, T.; Saito, N.; Yamada,
Y.; Asao, T.; Oki, T. J. Antiobiot. 2000, 53, 337.
7. (a) Schmid, H.; Eisenhuth, W. Helv. Chim. Acta 1958, 41, 2021; (b) Webb, A. D.;
Harris, T. M. Tetrahedron Lett. 1977, 24, 2069; (c) Naruta, Y.; Uno, H.;
Maruyama, K. J. Chem. Soc., Chem. Commun. 1981, 1277; (d) Kometani, T.;
Yoshii, E. J. Chem. Soc., Perkin Trans. 1 1981, 1191; (e) Kometani, T.; Yoshii, E. J.
Chem. Soc., Perkin Trans. 1 1981, 1197; (f) Giles, R. G. F.; Green, I. R.; Hugo, V. I.;
Mitchell, P. R. K. J. Chem. Soc., Chem. Commun. 1983, 51; (g) Giles, R. G. F.; Green,
I. R.; Hugo, V. I.; Yorke, S. C.; Mitchell, P. R. K. J. Chem. Soc., Perkin Trans. 1 1984,
2383. (h) Kraus, G. A.; Molina, M. T.; Walling, J. A. J. Chem. Soc., Chem. Commun.
1986, 1568; (i) Uno, H. J. Org. Chem. 1986, 51, 350; (j) Kobayashi, K.; Uchida, M.;
Uneda, T.; Tanmatsu, M.; Morikawa, O.; Konishi, H. Tetrahedron Lett. 1998, 39,
7725; For a review see: (k) Brimble, M. A.; Nairn, M. R.; Prabaharan, H.
Tetrahedron 2000, 56, 1937.
8. (a) Tewierik, L. M.; Dimitriadis, C.; Donner, C. D.; Gill, M.; Willems, B. Org.
Biomol. Chem. 2006, 4, 3311; (b) Gibson, J. S.; Andrey, O.; Brimble, M. A.
Synthesis 2007, 2611.
9. Dimitriadis, C.; Gill, M.; Harte, M. F. Tetrahedron: Asymmetry 1997, 8, 2153.
10. (a) Hauser, F. M.; Rhee, R. P. J. Org. Chem. 1978, 43, 178; (b) Kraus, G. A.;
Sugimoto, H. Tetrahedron Lett. 1978, 2263.
23. Data for 9b: Pale yellow oil; ½a D25
ꢂ
+37.5 (c 1.2, CHCl3); IR (CHCl3): m = 3022,
2934, 2835, 1715, 1654, 1594, 1497, 1462, 1374, 1262, 1213, 1108, 1067, 1012,
988, 757, 669 cmꢀ1 1H NMR (400 MHz, CDCl3/TMS): d 1.40 (d, 3H, J = 6.1 Hz,
;
CHCH3), 1.64 (d, 3H, J = 6.7 Hz, CHCH3), 2.61 (dd, 1H, J = 16.8, 10.9 Hz, CHaxH),
3.08 (dd, 1H, J = 16.8, 3.4 Hz, CHeqH), 3.81 (s, 3H, OCH3), 3.85 (s, 3H, OCH3), 4.01
(s, 3H, OCH3), 4.15 (m, 1H, CH2CHCH3), 5.34 (q, 1H, J = 6.7 Hz, CHCH3), 6.84 (d,
1H, J = 7.2 Hz, H-Ar), 7.38 (dd, 1H, J = 8.0, 7.6 Hz, H-Ar), 7.66 (dd, 1H, J = 8.1,
1 Hz, H-Ar); 13C NMR (100 MHz, CDCl3/CHCl3):
d 20.89 (CHCH3), 22.26
(CHCH3), 30.75 (CH2), 56.15 (OCH3), 60.74 (OCH3), 62.03 (OCH3), 62.40 (CH),
69.00 (CH), 105.45 (Ar), 114.64 (Ar), 119.26 (Ar), 124.44 (Ar), 125.82 (Ar),
129.97 (Ar), 130.12 (Ar), 148.12 (Ar), 149.05 (Ar), 156.12 (Ar); MS (I): m/e = 303
[M++1] (100), 288 (5), 229 (2); Calcd for C18H22O4 (302.37): C, 71.50; H, 7.33.
Found: C, 71.41; H, 7.44.
24. Data for 3: Yellow needles; mp 168–170 °C; ½a D25
ꢂ
+65.6 (c 0.3, CHCl3); IR
m = 3016, 2923, 2852, 1717, 1657, 1586, 1470, 1375, 1256, 1216, 1054,
(CHCl3):
927, 760, 669 cmꢀ1 1H NMR (400 MHz, CDCl3/TMS): d 1.36 (d, 3H, J = 6.1 Hz,
;
CHCH3), 1.55 (d, 3H, J = 6.7 Hz, CHCH3), 2.27 (ddd, 1H, J = 18.9, 10.2, 2.1 Hz,
CHaxH), 2.72 (dd, 1H, J = 19.1, 3.5 Hz, CHeqH), 3.98 (m, 1H, CH2CHCH3), 4.01 (s,
3H, OCH3), 5.03 (q, 1H, J = 6.7 Hz, CHCH3), 7.29 (d, 1H, J = 8.5 Hz, H-Ar), 7.66
(dd, 1H, J = 8.1, 7.6 Hz, H-Ar), 7.76 (dd, 1H, J = 7.6, 1 Hz, H-Ar); 13C NMR
(100 MHz, CDCl3/CHCl3): d 19.87 (CHCH3), 21.62 (CHCH3), 29.62 (CH2), 56.56
(OCH3), 62.57 (CH), 67.52 (CH), 117.93 (Ar), 119.20 (Ar), 119.8 (Ar), 134.17 (Ar),
134.83 (Ar), 139.47 (Ar), 148.13 (Ar), 159.83 (Ar), 182.84 (C@O), 184.34 (C@O);
MS (I): m/e = 273 [M++1] (6), 243 (2), 229 (100), 201 (1.5); Calcd for C16H16O4
(272.3): C, 70.57; H, 5.92. Found: C, 70.25; H, 5.86.