Total synthesis of (±)-heliannuol C and E via aromatic Claisen rearrangement

Article abstract of DOI:10.1016/j.tetlet.2005.02.053

The total synthesis of heliannuol C and E from a common intermediate are described. Key steps in the synthesis include a regioselective aromatic Claisen rearrangement to install the (1-vinyl)-4-methyl-3-pentenyl substituent and regioselective biomimetic 7

Full text of DOI:10.1016/j.tetlet.2005.02.053

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 2457–2460
Total synthesis of ( )-heliannuol C and E via
aromatic Claisen rearrangement
James R. Vyvyan,* Jennifer M. Oaksmith, Bevin W. Parks and Elaine M. Peterson
Department of Chemistry, Western Washington University, Bellingham, WA 98225, USA
Received 14 September 2004; accepted 9 February 2005
Abstract—The total synthesis of heliannuol C and E from a common intermediate are described. Key steps in the synthesis include a
regioselective aromatic Claisen rearrangement to install the (1-vinyl)-4-methyl-3-pentenyl substituent and regioselective biomimetic
7-endo and 6-exo phenol epoxide cyclizations to form the cyclic ether moieties.
Ó 2005 Elsevier Ltd. All rights reserved.
Although the term allelopathy was first used in 1937, the
chemical interaction between plants has been known for
thousands of years.1 Allelochemicals that suppress or
eliminate competing plant species near the source plant
have received special attention due to the agricultural
potential of these compounds as selective natural herbi-
cides.2 The heliannuols (1–12, Fig. 1) are a promising
group of phenolic allelochemicals isolated from
Helianthus annuus that exhibit activity against dicotyle-
don plant species.3 Heliannuols A (1) and C (3) are
the most active members of the family, with effective
concentrations as low as 10À9 M for germination inhibi-
tion of lettuce and cress, while heliannuol E (5) exhibits
weaker activity.3b,4 The unusual structures and agricul-
tural potential of the heliannuols have attracted signifi-
cant attention from the synthetic community.5 Herein
we report the total synthesis of ( )-heliannuol C (3)
and ( )-heliannuol E (5).6
We envisioned preparing both heliannuol C (3) and E
(5) via biomimetic phenol–epoxide cyclizations.3b
A 7-endo-cyclization of the phenol onto the more substi-
tuted position of the appropriate diastereomer of
epoxide 13 would lead to 3 (Fig. 2). Similarly, heli-
annuol E (5) would be made via 6-exo-cyclization of
the phenol group to the less substituted epoxide position
of 13.5a–c,h Epoxide 13 would be prepared by selective
epoxidation of diene 14, which in turn would be pre-
pared via Claisen rearrangement of aryl allyl ether 15.
Mitsunobu etherification7 of 4-methoxy-3-methylphenol
(16)8 with E -6-methyl-2,5-heptadien-1-ol (17)9 afforded
Figure 1. Structures of the heliannuols.
Keywords: Allelopathy; Biomimetic reactions; Epoxides; Herbicides;
Oxygen heterocycles.
*
Corresponding author. Tel.: +1 360 650 2883; fax: +1 360 650
2826; e-mail: vyvyan@chem.wwu.edu
Figure 2. Retrosynthesis of heliannuols C and E.
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.02.053

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J. R. Vyvyan et al. / Tetrahedron Letters 46 (2005) 2457–2460
(BBr3,17 NaSEt,18 NaSPh19) all failed in this case, result-
ing in complex mixtures of compounds formed by
decomposition of the starting material. Treatment of
18 with excess neat MeMgI at high temperatures,20 how-
ever, afforded heliannuol E (5) and its diastereomer 21 in
41% combined yield after purification (Table 1, entry 1).
The highly basic nature of this method, however, led to
the formation of side products containing an isomerized
olefin (cf. 19 and 20 above).
Reaction of 18 with triethylsilane in the presence of
a catalytic amount of B(C6F5)3 at room temperature
followed by treatment of the reaction mixture with
TBAF21 provided 5 and 2122 in a much improved
74% combined yield (Table 1, entry 2). A consider-
able amount of tertiary triethylsilyl ether 22 was also
obtained, even after prolonged exposure to TBAF in
THF, but it was found that treatment of 22 with HF/
CH3CN yielded ( )-heliannuol E (5). Using HF/CH3CN
instead of TBAF in the deprotection of 18 resulted in
exclusive formation of 5 and 21, but in lower overall
yield (Table 1, entry 3). The IR, 1H, and 13C NMR spec-
tral data of 5 were in complete agreement with those
reported for the natural product3c,23 and in previous
syntheses.5c,f,g,m
Scheme 1. Preparation of cyclization precursor 13.
diene ether 15,10,11 in good to excellent yield (Scheme 1).
Claisen rearrangement of 15 produced diene phenol 1412
as a single regioisomer in good yield when the reaction
was done at low temperature. Adding m-CPBA in small
portions to a cold, buffered solution of 14 selectively oxi-
dized the more substituted olefin to yield diastereomeric
epoxides 13 in quantitative yield.13,5a Unfortunately we
were not able to easily separate the diastereomers at this
stage and the diastereomeric mixture was used directly
in the subsequent cyclization reactions.
Treatment of epoxide 13 with SnCl4 resulted in a regio-
selective 7-endo-cyclization24 to form the separable
benzoxepanes 23 and 24 (Scheme 3).25 Deprotection of
the methyl ether group in 23 using the triethylsilane/cata-
lytic B(C6F5)3 system employed above21 provided ( )-
heliannuol C (3). The yield of 3 was slightly lower when
HF/CH3CN was used in the final step of the deprotec-
tion (31–36%) as compared to HF–pyridine (53–57%).
Subjecting 24 to the same ether cleavage protocol affor-
ded epi-heliannuol C (25)26 in similar yields.
The conditions used previously for a 7-exo-cyclization in
our synthesis of heliannuol D5a resulted in a 6-exo-cycli-
zation to produce 18 when the reaction was done on a
small scale, but when the reaction was repeated with
more material, the pendant olefin migrated into conju-
gation with the aromatic ring14 to form mixtures of 19
and 20 (Scheme 2).15 The ring-opened compound 20
was the major product at higher temperatures. Using a
weaker base in the reaction5c resulted in a relatively
clean 6-exo-cyclization that provided chromane deriva-
tive 1816 in good yield, but the diastereomers remained
inseparable at this stage. Cleavage of the methyl ether
group in 18 proved to be a difficult transformation.
Many commonly employed demethylation procedures
Table 1. Deprotection of 18; synthesis of ( )-heliannuol E
MeO
K2CO3
13
MeOH
O
OH
63 %
18
KOH
Entry
Conditions
%Yield
DMSO
521
H
H
H
1
2
CH3Mgl (15 equiv), 170–190 °C
(i) Et3SiH, B(C6F5)3 (cat), CH2Cl2
(ii) TBAF, THF, room temp
(i) Et3SiH, B(C6F5)3 (cat), CH2Cl2
(ii) HF, CH3CN
12
29
37
19
H
MeO
MeO
37
20
3
O
OH
OH
% yield
OH
19
20
Temp
70 °C
90 °C
74
14
arrows show observed NOEs
10
62
Scheme 2. Base-promoted reactions of epoxide 13.

J. R. Vyvyan et al. / Tetrahedron Letters 46 (2005) 2457–2460
2459
M.; Torres, A.; Fronczek, F. R. J. Org. Chem. 1994, 59,
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8261–8266; (c) Macıas, F. A.; Varela, R. M.; Torres, A.;
Molinillo, J. M. G. Tetrahedron Lett. 1999, 40, 4725–4728;
´
(d) Macıas, F. A.; Varela, R. M.; Torres, A.; Molinillo, J.
M. G. J. Nat. Prod. 1999, 62, 1636–1639; (e) Macıas, F.
´
A.; Varela, R. M.; Torres, A.; Molinillo, J. M. G. J. Chem.
´
Ecol. 2000, 26, 2173–2186; (f) Macıas, F. A.; Torres, A.;
Galindo, J. L. G.; Varela, R. M.; Alvarez, J. A.; Molinillo,
J. M. G. Phytochemistry 2002, 61, 687–692.
´
4. Macıas, F. A.; Molinillo, J. M. G.; Chinchilla, D.; Galindo,
J. C. G. In Allelopathy: Chemistry and Mode of Action of
´
Allelochemicals; Macıas, F. A., Molinillo, J. M. G.,
Galindo, J. C. G., Eds.; CRC: Boca Raton, 2004; Chapter 5.
5. (a) Vyvyan, J. R.; Looper, R. E. Tetrahedron Lett. 2000,
41, 1151–1154; (b) Takabatake, K.; Nishi, I.; Shindo, M.;
Shishido, K. J. Chem. Soc., Perkin Trans. 1 2000, 1807–
1808; (c) Sato, K.; Yoshimura, T.; Shindo, M.; Shishido,
K. J. Org. Chem. 2001, 66, 309–314; (d) Tuhina, K.;
Bhowmik, D. R.; Venkateswaran, R. V. Chem. Commun.
2002, 634–635; (e) Kishkuku, H.; Shindo, M.; Shishido, K.
Chem. Commun. 2003, 350–351; (f) Doi, F.; Ogamino, T.;
Sugai, T.; Nishiyama, S. Synlett 2003, 411–413; (g) Doi,
F.; Ogamino, T.; Sugai, T.; Nishiyama, S. Tetrahedron
Scheme 3. Synthesis of ( )-heliannuol C (3) and its epimer 25.
´
Lett. 2003, 44, 4877–4880; (h) Macıas, F. A.; Chinchilla,
D.; Molinillo, J. M. G.; Marin, D.; Varela, R. M.; Torres,
A. Tetrahedron 2003, 59, 1679–1683; (i) Kishuku, H.;
Yoshimura, T.; Kakehashi, T.; Shindo, M.; Shishido, K.
Heterocycles 2003, 61, 125–131; (j) Sabui, S. K.; Venka-
teswaran, R. V. Tetrahedron 2003, 59, 8375–8381; (k)
Sabui, S. K.; Venkateswaran, R. V. Tetrahedron Lett.
2004, 45, 983–985; (l) Sabui, S. K.; Venkateswaran, R. V.
Tetrahedron Lett. 2004, 45, 2047–2048; (m) Kamei, T.;
Shindo, M.; Shishido, K. Synlett 2003, 2395–2397; (n)
Kamei, T.; Shindo, M.; Shishido, K. Tetrahedron Lett.
2003, 44, 8505–8507; (o) Doi, F.; Ohara, T.; Ogamino, T.;
Sugai, T.; Higashinakasu, K.; Yamada, K.; Shigemori, H.;
Hasegawa, K.; Nishiyama, S. Phytochemistry 2004, 65,
The room temperature 13C NMR spectra of benzoxe-
pane compounds 3 and 23–25 contain three very broad,
almost indiscernible resonances corresponding to the
benzylic methine and the geminal methyl groups. These
signals sharpen somewhat at elevated temperature, indi-
cating a conformational exchange process occurring in
solution on an intermediate time scale.27 Thorough
comparison of NMR spectral data from natural
(À)-heliannuol C with those obtained from our syn-
thetic ( )-3, however, showed that the samples were
identical.28
´
1405–1411; (p) Lecornue, F.; Ollivier, J. Synlett 2004,
1613–1615.
6. Drew, J. A.; Peterson, E. M.; Oaksmith, J. M.; Parks, B.
W.; Vyvyan, J. R. Abstracts of Papers, 225th National
Meeting of the American Chemical Society, New Orleans,
LA; American Chemical Society: Washington, DC, 2003;
ORGN 417.
In summary, the aromatic Claisen rearrangement of
diene 15 results in rapid construction of the heliannuol
C/E skeleton. ( )-Heliannuol E (5) was prepared in 9%
yield and ( )-heliannuol C (3) in 15% yield over seven
linear steps each from 2-methylanisole.
7. Mitsunobu, O. Synthesis 1981, 1–28.
8. Prepared in two steps from 2-methylanisole. See: Vyvyan,
J. R.; Loitz, C.; Looper, R. E.; Mattingly, C. S.; Peterson,
E. A.; Staben, S. T. J. Org. Chem. 2004, 69, 2461–2468.
9. (a) Yadav, J. S.; Praveen Kumar, T. K.; Maniyan, P. P.
Tetrahedron Lett. 1993, 34, 2965–2968; (b) Cahiez, C.;
Alexakis, A.; Normant, J. F. Synthesis 1978, 528–530.
10. All new compounds exhibited IR, 1H, and 13C NMR
spectra in agreement with the assigned structures.
11. Ether 15: 1H NMR: (300 MHz, CDCl3) d 6.72 (m, 3H),
5.76 (m, 2H), 5.16 (t of septets, J = 7.0, 1.5 Hz, 1H), 4.40
(m, 2H), 3.78 (s, 3H), 2.77 (br t, J = 6.2 Hz, 2H), 2.19 (s,
3H), 1.71 (s, 3H), and 1.62 (s, 3H); 13C NMR: (75 MHz,
CDCl3) d 152.4, 152.0, 133.7, 133.0, 127.7, 125.1, 121.3,
118.0, 111.8, 110.7, 69.3, 55.8, 31.0, 25.7, 17.7, and 16.4.
Anal. Calcd for C16H22O2: C, 78.01; H, 9.00. Found: C,
78.26; H, 8.85.
Acknowledgements
´
The authors thank Francisco A. Macıas for NMR spec-
tra of (À)-heliannuol C and Kozo Shishido for helpful
correspondence. The authors thank the NSF (CHE-
0094378) and the Herman Frasch Foundation for finan-
cial support. The 500 MHz NMR used in this study was
purchased through NSF-MRI grant CHE-0216604. We
also thank Jennifer A. Meyer for acquiring some of the
NMR data.
References and notes
1
1. Rice, E. L. Allelopathy, 2nd ed.; Academic: New
York, 1984; pp 1–7.
2. (a) Vyvyan, J. R. Tetrahedron 2002, 58, 1631–1646; (b)
Duke, S. O.; Dayan, F. E.; Romagni, J. G.; Rimando, A.
M. Weed Res. 2000, 40, 99–111.
12. Phenol 14: H NMR: (300 MHz, CDCl3) d 6.62 (s, 1H),
6.58 (s, 1H), 6.03 (ddd, J = 17.0, 10.6, 6.4 Hz, 1H), 5.13
(m, 3H), 4.62 (s, 1H), 3.77 (s, 3H), 3.51 (br q, J = 6.5 Hz,
1H), 2.44 (m, 2H), 2.16 (s, 3H), 1.67 (d, J = 1.0 Hz, 3H),
and 1.59 (br s, 3H); 13C NMR: (75 MHz, CDCl3) d 151.9,
146.9, 140.9, 133.0, 127.0, 125.6, 122.2, 118.8, 114.8, 110.9,
56.1, 43.8, 32.2, 25.7, 17.9, and 15.7. Anal. Calcd for
C16H22O2: C, 78.01; H, 9.00. Found: C, 78.08; H, 9.11.
´
3. (a) Macıas, F. A.; Varela, R. M.; Torres, A.; Molinillo, J.
M. G.; Fronczek, F. R. Tetrahedron Lett. 1993, 34, 1999–
´
2002; (b) Macıas, F. A.; Molinillo, J. M. G.; Varela, R.

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J. R. Vyvyan et al. / Tetrahedron Letters 46 (2005) 2457–2460
1
13. Epoxide 13: H NMR: (300 MHz, CDCl3) d (mixture of
diastereomers) 6.64 (s, 0.5H), 6.61 (s, 0.5H), 6.60 (s, 0.5H),
6.58 (s, 0.5H), 6.09 (m, 1H), 5.19 (m, 2H), 4.94 (s, 0.5H),
4.79 (s, 0.5H), 3.78 (s,1.5H), 3.77 (s, 1.5H), 3.73 (m, obs,
1H), 2.80 (t, J = 6.2 Hz, 0.5H), 2.73 (t, J = 6.2 Hz, 0.5H),
2.16 (s, 1.5H), 2.15 (s, 1.5H), 1.99 (m, 2H), 1.29 (s, 1.5H),
1.28 (s, 1.5H), 1.21 (s, 1.5H), and 1.12 (s, 1.5H); 13C
NMR: (75 MHz, CDCl3) d (mixture of diastereomers)
151.52, 151.46, 147.2, 147.0, 140.6, 140.1, 126.9, 126.4,
125.6, 25.5, 118.6, 118.5, 114.8, 114.4, 110.9, 110.4, 63.6,
63.4, 59.7, 9.6, 56.0 (2C), 40.9, 40.5, 33.1, 32.9, 24.7, 24.6,
18.7, 18.5, and 15.7 (2C).
2541–2547; (d) Chakraborti, A. K.; Sharma, L.; Nayak,
M. K. J. Org. Chem. 2002, 67, 6406–6414.
20. (a) Wilds, A. L.; McCormack, W. B. J. Am. Chem. Soc.
1948, 70, 4127; (b) Hoye, T. R.; Humpal, P. E.; Moon, B.
J. Am. Chem. Soc. 2000, 122, 4933–4982.
21. Gevorgyan, V.; Rubin, M.; Benson, S.; Liu, J.-X.;
Yamamoto, Y. J. Org. Chem. 2000, 65, 6179–6186.
22. Compound 21: 1H NMR: (300 MHz, CDCl3) d 6.62 (s,
1H), 6.54 (s, 1H), 5.66 (dt, J = 17.0, 10.0 Hz, 1H), 5.23
(ddd, J = 17.0, 1.7, 0.6, Hz, 1H), 5.10 (dd, J = 10.0, 1.7 Hz,
1H), 4.40 (br s, 1H), 3.79 (dd, J = 11.5, 1.5 Hz, 1H), 3.47
(br m, 1H), 2.4 (br s, 1H), 2.18 (s, 3H), 2.02 (ddd, J = 13.2,
5.9, 1.5 Hz, 1H), 1.65 (ddd, J = 13.2, 11.7, 11.7 Hz, 1H),
1.31 (s, 3H), and 1.26 (s, 3H); 13C NMR: (75 MHz, CDCl3)
d 147.9, 147.5, 140.7, 123.9, 122.1, 118.5, 116.7, 114.5, 81.5,
71.9, 41.0, 30.0, 25.8, 24.2, and 15.6.
14. (a) Pines, H.; Stalick, W. M. Olefin Isomerization. Base-
Catalyzed Reactions of Hydrocarbons and Related Com-
pounds; Academic: New York, 1977; pp 25–123; (b) Ela, S.
W.; Cram, D. J. J. Am. Chem. Soc. 1966, 88, 5791–5802.
15. Compound 19: 1H NMR: (500 MHz, CDCl3) d 6.91 (s,
1H), 6.67 (s, 1H), 6.07 (qd, J = 7.3, 1.5 Hz, 1H), 3.79 (s,
3H), 3.68 (dd, J = 12.7, 2.4 Hz, 1H), 2.80 (dd, J = 15.1,
2.0 Hz, 1H), 2.45 (s, 1H), 2.26 (dddq, J = 15.1, 12.7, 2.4,
1.5 Hz, 1H), 2.16 (s, 3H), 1.79 (dd, J = 7.3, 1.5 Hz, 3H),
1.34 (s, 3H), and 1.30 (s, 3H); 13C NMR: (125 MHz,
CDCl3) d 152.2 (C), 147.7 (C), 129.2 (C), 127.6 (C), 120.1
(C), 119.2 (CH), 116.0 (CH), 104.0 (CH), 81.9 (CH), 71.7
(C), 55.7 (CH3), 25.9 (CH3), 25.5 (CH2), 24.5 (CH3), 15.9
(CH3), and 13.2 (CH3). Compound 20: mp = 106–109 °C;
1H NMR: (300 MHz, CDCl3) d 6.82 (d, J = 15.6 Hz, 1H),
6.72 (s, 1H), 6.51 (s, 1H), 5.69 (br q, J = 7.1 Hz, 1H), 5.63
(d, J = 15.6 Hz, 1H), 4.70 (br s, 1H), 3.76 (s, 3H), 2.21 (s,
3H), 1.95 (d, J = 7.1 Hz, 3H), and 1.33 (s, 6H); 13C NMR:
(75 MHz, CDCl3) d 151.5, 146.2, 141.5, 135.1, 129.8,
127.1, 125.0, 121.2, 117.7, 112.3, 71.1, 55.9, 29.9 (2C),
16.0, and 13.8; Anal. Calcd for C16H22O3: C, 73.25; H,
8.45. Found: C, 73.52; H, 8.68.
23. Our pure ( )-5 is a solid (mp = 104–106 °C) whereas
natural (À)-5 is reported to be an oil. See Refs. 3c,5c.
24. Cushing, T. D.; Sanz-Cevera, J. F.; Williams, R. M.
J. Am. Chem. Soc. 1996, 118, 557–579.
25. Compound 23: 1H NMR: (500 MHz, CDCl3) d 6.72 (s,
1H), 6.53 (s, 1H), 6.13 (ddd, J = 17.2, 10.2, 7.3 Hz, 1H),
5.11 (br d, J = 10.2 Hz, 1H), 5.01 (br d, J = 17.2 Hz, 1H),
3.81 (m, 1H), 3.78 (s, 3H), 3.60 (br m, 1H), 2.14 (s, 3H),
2.02 (ddd, J = 13.8, 7.7, 3.3 Hz, 1H), 1.95 (ddd, J = 13.8,
9.0, 3.3 Hz, 1H), 1.30 (s, 3H), and 1.15 (s, 3H); 13C NMR:
(125 MHz, CDCl3, 45 °C) d 153.9 (C), 147.3 (C), 139.7
(CH), 133.8 (C), 126.3 (CH), 125.2 (C), 115.2 (CH2), 110.1
(CH), 79.7 (C), 74.6 (CH), 55.6 (CH3), 42.8 (CH), 36.1
(CH2), 26.7 (CH3), 21.1 (CH3), and 15.7 (CH3). Com-
pound 24: 1H NMR: (500 MHz, CDCl3) d 6.75 (s, 1H),
6.25 (s, 1H), 6.21 (ddd, J = 17.1, 10.3, 6.8 Hz, 1H), 5.15 (br
d, J = 10.3 Hz, 1H), 4.96 (br d, J = 17.1 Hz, 1H), 3.77 (s,
3H), 3.76 (m, 1H), 3.54 (br t, J = 6.5 Hz, 1H), 2.15 (s, 3H),
2.08 (dt, J = 13.8, 3.5 Hz, 1H), 1.93 (m, 1H), 1.31 (s, 3H),
and 1.13 (s, 3H); 13C NMR: (125 MHz, CDCl3, 45 °C) d
153.9 (C), 147.5 (C), 141.0 (CH), 133.5 (C), 126.3 (CH),
125.2 (C), 114.9 (CH2), 109.9 (CH), 79.3 (C), 78.1 (CH),
55.6 (CH3), 43.2 (CH), 35.8 (CH2), 26.4 (CH3), 21.6
(CH3), and 15.9 (CH3).
1
16. Compound 18: H NMR: (300 MHz, CDCl3) d (mixture
of diastereomers) 6.67 (s, 0.5H), 6.65 (s, 0.5H), 6.57 (s,
0.5H), 6.48 (s, 0.5H), 5.99 (ddd, J = 17.0, 10.0, 6.3 Hz,
0.5H), 5.70 (ddd, J = 17.0, 10.0, 9.1 Hz, 0.5H), 5.26 (ddd,
J = 17.0, 1.7, 0.6 Hz, 0.5H), 5.19 (dd, J = 10.0, 1.7 Hz,
0.5H), 5.10 (dt, J = 10.0, 1.5 Hz, 0.5H), 4.91 (dt, J = 17.0,
1.5 Hz, 0.5H), 3.79 (dd, J = 11.5, 1.5 Hz, 0.5H), 3.74 (dd,
J = 11.4, 2.4 Hz, 0.5H), 3.746 (s, 1.5 H), 3.737 (s, 1.5H),
3.50 (br m, 1H), 2.4 (br s, 1H), 2.16 (s, 1.5H), 2.15 (s,
1.5H), 2.03 (ddd, J = 13.2, 5.9, 1.5 Hz, 0.5H), 1.89 (m,
1H), 1.65 (ddd, J = 13.2, 11.8, 11.8 Hz, 0.5H), 1.30 (s,
1
26. Compound 25: H NMR: (500 MHz, CD3OD) d 6.62 (s,
1H), 6.52 (s, 1H), 6.10 (ddd, J = 17.1, 10.0, 8.5 Hz, 1H),
5.17 (dd, J = 10.0, 1.5 Hz, 1H), 5.12 (d, J = 17.1 Hz, 1H),
4.65 (br s, 1H), 3.66 (dd, J = 11.1, 3.5 Hz, 1H), 3.42 (br t,
J = 9.6 Hz, 1H), 2.10 (s, 3H), 1.93 (ddd, J = 13.5, 3.5,
2.5 Hz, 1H), 1.64 (dt, J = 13.5, 11.1 Hz, 1H), 1.42 (s, 3H),
and 0.89 (s, 3H); 13C NMR: (125 MHz, CD3 OD, 50 °C) d
152.7 (C), 147.7 (C), 142.3 (CH), 136.6 (C), 127.2 (CH),
123.8 (C), 115.2 (CH2), 114.2 (CH), 81.0 (C), 78.9 (CH),
43.0 (CH), 38.5 (CH2), 29.0 (CH3), 19.0 (CH3), and 15.9
(CH3).
1.5H), 1.29 (s, 1.5H), 1.26 (s, 1.5H), and 1.24 (s, 1.5H); 13
C
NMR: (75 MHz, CDCl3) d (mixture of diastereomers)
151.7, 151.6, 148.0, 147.7, 142.3, 140.9, 126.7, 126.6, 121.1,
119.7, 118.7, 118.6, 116.6, 115.8, 111.5, 110.1, 81.4 (2C),
71.7 (2C), 55.8 (2C), 41.2, 38.2, 30.1, 27.5, 25.8, 25.7, 24.4,
24.3, 15.9, and 15.8.
17. McOmie, J. F. W.; Watts, M.; West, D. E. Tetrahedron
1968, 24, 2289–2292.
18. Feutrill, G. I.; Mirrington, R. N. Aust. J. Chem. 1972, 25,
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27. The corresponding resonances in the 1H NMR spectra of 3
´
and 23–25 are only slightly broadened. Neither Macıas
(Ref. 3b) nor Shishido (Ref. 5n) comment on this
phenomenon, but MacıasÕ 13C NMR spectrum of (À)-3
´
exhibits the same broadening observed by us.
28. Our pure ( )-3 is a solid (mp = 184–188 °C) and is only
sparingly soluble in CDCl3, in contrast to the properties
´
reported by Macıas for natural (À)-heliannuol C. See Ref.
3b.