Reactions of verbenol epoxide with aromatic aldehydes containing hydroxy or methoxy groups in the presence of montmorillonite clay

Article abstract of DOI:10.1002/hlca.201000269

The reactions of (-)-cis-verbenol epoxide with a number of aromatic aldehydes containing OH and/or MeO groups in the presence of montmorillonite K10 clay have been studied. Several new O-containing heterocyclic compounds with different frameworks, including compounds with a previously unknown octahydro-2H-4,6-(epoxymethano)chromene framework, have been synthesized. Introduction of one donor substituent in the benzaldehyde molecule led to a decrease in the total yield of intermolecular by formed products, while the introduction of two and more substituents led to an increase in the yield of these products.

Full text of DOI:10.1002/hlca.201000269

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Helvetica Chimica Acta – Vol. 94 (2011)
Reactions of Verbenol Epoxide with Aromatic Aldehydes Containing
Hydroxy or Methoxy Groups in the Presence of Montmorillonite Clay
by Irina V. Ilꢀinaa), Konstantin P. Volcho*a), Oksana S. Mikhalchenkob), Dina V. Korchaginaa), and
Nariman F. Salakhutdinova)
a) N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of
Sciences, Lavrentiev ave., 9, 630090 Novosibirsk, Russian Federation
(fax: þ 73833309752; e-mail: volcho@nioch.nsc.ru)
b) Novosibirsk State University, Pirogov st., 2, 630090 Novosibirsk, Russian Federation
The reactions of (ꢀ)-cis-verbenol epoxide with a number of aromatic aldehydes containing OH and/
or MeO groups in the presence of montmorillonite K10 clay have been studied. Several new O-
containing heterocyclic compounds with different frameworks, including compounds with a previously
unknown octahydro-2H-4,6-(epoxymethano)chromene framework, have been synthesized. Introduction
of one donor substituent in the benzaldehyde molecule led to a decrease in the total yield of
intermolecular by formed products, while the introduction of two and more substituents led to an
increase in the yield of these products.
Introduction. – Pinene terpenoids are valuable recyclable raw materials. Due to
their unique structure combined with high chemical lability and optical activity, they
often serve as substrates for the synthesis of complex optically active compounds [1 –
5], including compounds with biological activity [6 – 9]. In acidic media, pinene
terpenoids generally undergo numerous transformations leading to complex mixtures
of products, which is one of the factors hindering the wide use of these compounds in
fine organic chemistry. At the same time, the product ratio significantly depends on the
type and characteristics of the acid catalysts used, and this occasionally allows one to
select favorable conditions for the formation of a desired compound, stimulating the
search for new catalytic systems and reaction conditions [10 – 14]. Clays play an
especially important role among the acid catalysts in terpenoid transformations. On the
one hand, these are inexpensive and accessible compounds, which allow ecologically
clean synthesis; on the other hand, they often direct terpenoid transformations by new
routes or lead to other product ratios compared with other acid catalysts [15 – 20].
Earlier, we studied the intermolecular reactions of several terpenoids from pinene,
p-menthene, and carene series with aldehydes in the presence of montmorillonite clays
(K10 and the natural askanite-bentonite clay) [21 – 24]. As a result, we found unusual
transformations, which occur during the reactions of terpene olefins and their
derivatives with aldehydes, and form generally complex optically active heterocyclic
compounds from simple reagents. The structure of the products depends strongly on
small changes in the structure of both starting terpenoids and aldehydes.
For example, it was found [23] that the reaction of (ꢀ)-cis-verbenol epoxide (1),
obtained from the widespread monoterpene a-pinene, with 4-methoxybenzaldehyde
ꢀ 2011 Verlag Helvetica Chimica Acta AG, Zꢁrich

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(2a) and 2-hydroxybenzaldehyde (2b) in the presence of the natural montmorillonite
clay askanite-bentonite gave not only the products of isomerization of epoxide 1 (trans-
diol with a p-menthane framework 3 and hydroxy ketone 4), but also the products of
the intermolecular interaction with the aldehyde, i.e., 1,3-benzodioxins 5a and 5b (with
yields of 13 and 14%, resp.; Scheme 1). The hypothetical mechanism of the formation
of 5a and 5b involves the protonation and cleavage of the epoxide ring, the skeletal
rearrangement into the cation with a p-menthane framework A, and its subsequent
interaction with the aldehyde molecule, which acts as a nucleophile.
Scheme 1. Interaction of (ꢀ)-cis-Verbenol Epoxide (1) with 4-Methoxybenzaldehyde (2a) and 2-
Hydroxybenzaldehyde (2b) on Askanite-Bentonite Clay [23]
This work represents a continuation of our studies of this unusual reaction. The aim
of this study was to investigate the influence of the structure of the aldehyde on the
route of transformations. We examined the transformations of (ꢀ)-cis-verbenol
epoxide (1) in the presence of the commercially accessible montmorillonite clay K10
with benzaldehyde and a number of aromatic aldehydes containing a OH and/or MeO
group. Due to the presence of these donor substituents in the aldehydes, the reactivity
of the latter in nucleophilic reactions increases; moreover the products can exhibit high
biological activity, because several bioactive compounds contain in their structures
terpene moieties and an aromatic ring with O-containing substituents in their structure
[25 – 28].
Results and Discussion. – We started our studies with the reaction of benzaldehyde
(2c) in order to investigate how the introduction of substituents affects the route of
transformations.

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The reaction of (ꢀ)-cis-verbenol epoxide (1) with benzaldehyde (2c) on K10 clay
gave the known products of the epoxide isomerization, namely, trans-diol 3 and
hydroxy ketone 4, as well as the products of the intermolecular interaction of aldehyde
and terpenoid, i.e., compound 5c with a 1,3-benzodioxin framework, which is an analog
of 5a and 5b, and compounds 6a and 6b with a chromene framework as a mixture of
diastereoisomers according to the position of substituents at C(5) (6a/6b 3 :1;
Scheme 2).
Scheme 2. Interaction of Epoxide 1 with Aldehydes 2c – 2e on K10 Clay
The formation of 6a/6b was quite unexpected, because such products had not been
observed before in the reaction of 1 with 4-methoxybenzaldehyde (2a) and 2-
hydroxybenzaldehyde (2b) on clay [23].
In the reaction of 1 with 4-hydroxybenzaldehyde (2d), an isomer of 2b, the main
transformation was the formation of 3 and 4, as well as a-hydroxy aldehyde 7, which
was previously obtained in studies of the isomerization of epoxide 1 on clay [29]; the
intermolecular products were compounds 6c and 6d (6c/6d 8 :1), which are analogs of
6a and 6b (Scheme 2). Note that, in the reaction of 1 with 2d, compounds with a 1,3-
benzodioxin framework were not formed, in contrast to the reactions with 2-
hydroxybenzaldehyde (2b) and benzaldehyde (2c).
Thus, the introduction of one donor group in the aldehyde molecule led to a
decrease in the yields of intermolecular products compared with benzaldehyde (2c;
Schemes 1 and 2).
The addition of an additional MeO group to the aldehyde on passing from 4-
hydroxybenzaldehyde (2d) to 4-hydroxy-3-methoxybenzaldehyde (2e) led to a

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considerably increased total yield of intermolecular products 5e, and 6e and 6f (6e/6f
2 :1), and 6e and 6f were the major intermolecular products (Scheme 2).
Analyzing the possible mechanism of the formation of compounds of type 6
(Scheme 3), it can be assumed that diol 3 is an intermediate neutral species, while the
protonated aldehyde is an electrophile. The mechanism may include the formation of
cation B. Indeed, when diol 3 was stored on clay in the presence of aldehyde 2e, a
mixture of diastereoisomers, (3 :1), formed with a total yield of 50% based on changed
diol 3, whose conversion was 50%. This confirms our assumption that diol 3 can be an
intermediate in the formation of 6 from epoxide 1. Note that the use of diol 3 instead of
verbenol epoxide 1 for the preparation of 6e/6f facilitates the isolation of products and
leads to high yields.
Scheme 3. Possible Mechanism of the Formation of Compounds with Chromene Framework
In the reaction of 1 with 3-hydroxy-4-methoxybenzaldehyde (2f), an isomer of
aldehyde 2e, the major products were the products of the intermolecular interaction of
epoxide and aldehyde, compounds 6g/6h (1:1) and compound 5f. The reaction also led
to hydroxy ketone 4 and a-hydroxy aldehyde 7 (Scheme 4). Note that, in this reaction,
the reaction mixture did not contain trans-diol 3, probably because in this case 3
completely reacted with the aldehyde under the reaction conditions.
Scheme 4. Interaction of Epoxide 1 with Aldehyde 2f on K10 Clay
Unexpected results were obtained, when diol 3 was kept on K10 clay in the presence
of 2f (Scheme 5). First, the reaction mixture contained compound 5f; its formation

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from diol 3 might be rationalized by the fact that the protonation of 3 can form the
same cation A as the protonation and further isomerization of verbenol epoxide 1
(Scheme 1). Interaction of cation A with the aldehyde molecule can lead to the
formation of 5f. Second, in addition to products 6g/6h (5 :1) and 5f, the reaction
yielded the tricyclic compound 8a, which is the product of the addition of two aldehyde
molecules to 3. The hypothetical mechanism of its formation is presented in Scheme 5.
It involves the addition of protonated aldehyde 2f at the C¼C bond of 3 and
heterocyclization. Then, the formed cation interacts with a second aldehyde molecule.
Subsequent loss of Hþ and tautomerization of the enol group lead to the formation of
8a.
Scheme 5. Interaction of Diol 3 with Aldehyde 2f on K10 Clay
To the best of our knowledge, the octahydro-2H-4,6-(epoxymethano)chromene
framework of 8a is a novel structural motif.
The reaction of (ꢀ)-cis-verbenol epoxide (1) with 3,4,5-trimethoxybenzaldehyde
(2g) gave a mixture consisting of the products of epoxide isomerization 3, 4, and 7, and a
set of intermolecular products 5g, 6i/6k (1:1), and 8b (Scheme 6).
When diol 3 was stored on K10 clay in the presence of 2g, a mixture of heterocyclic
compounds 5g, 6i/6k (3 :1), and 8b formed, as in the case of aldehyde 2f (Scheme 7).
Conclusions. – We have studied the reactions of (ꢀ)-cis-verbenol epoxide (1) with a
number of aromatic aldehydes containing OH and/or MeO groups in the presence of
montmorillonite K10 clay. The introduction of one donor substituent in the
benzaldehyde molecule led to a decrease in the total yield of intermolecular products,
whereas the introduction of two and more substituents favors the formation of these
products. Using the accessible monoterpenoid 1 as a starting compound, we obtained a
set of new O-containing heterocyclic compounds with different types of framework,

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Scheme 6. Interaction of Epoxide 1 with Aldehyde 2g on K10 Clay
Scheme 7. Interaction of Diol 3 with Aldehyde 2g on K10 Clay
including compounds with a previously unknown octahydro-2H-4,6-(epoxymethano)-
chromene framework. Mechanisms of formation were proposed for all new products
and confirmed by the experimental model data.
The authors are grateful to the Presidium of Russian Academy of Sciences for financial support
(complex program No. 15.2) and Russian Foundation for Basic Research (grant No. 10-03-00230a).
Experimental Part
1. General. All materials were of commercial reagent grade. As catalyst, we used K10 clay (Merck).
The clay was calcinated at 1108 for 3 h immediately before use. CH2Cl2 was passed through calcined
20
Al2O3. (ꢀ)-cis-Verbenol epoxide (1) ([a] ¼ ꢀ60 (c ¼ 0.41, CHCl3)) was prepared according to [23]
580
from (ꢀ)-verbenone (Aldrich); the content of the main substance was not less than 98.0%. Column
chromatography (CC): silica gel (SiO2; 60 – 200 m; Macherey-Nagel). GC (purity control and product
analysis): Agilent 7820A; HP-5 quartz column (30000 ꢁ 0.25 mm), He (1 atm) as carrier gas. GC/MS:
Hewlett-Packard 5890/II gas chromatograph with a quadrupole mass spectrometer (HP MSD 5971) as a
detector, HP-5MS quartz column, 30000 ꢁ 0.25 mm, He (1 atm) as carrier gas. Optical rotation: polAAr
3005 spectrometer; CHCl3 soln. 1H- and 13C-NMR: Bruker DRX-500 apparatus at 500.13 (1H) and
125.76 MHz (13C), in CDCl3 or CDCl3/(D6)acetone 1:1 (v/v) soln.; chemical shifts d in ppm rel. to

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residual CHCl3 (d(H) 7.24 and d(C) 76.90 ppm), J in Hz; structure determinations by analyzing the
1
1H-NMR spectra, H,1H double resonance spectra, J-modulated 13C-NMR spectra (JMOD), 13C-NMR
spectra with H-atom off-resonance saturation and 13C,1H 2D-heteronuclear correlation with one-bond
and long-rang spin-spin coupling constants (C,H COSY, 1J(C,H) ¼ 135 Hz, COLOC, 2,3J(C,H) ¼ 10 Hz).
HR-MS: DFS-Thermo-Scientific spectrometer in a full-scan mode (0 – 500 m/z, 70 eV electron-impact
ionization (EI), direct sample introduction).
2. Reaction of (ꢀ)-cis-Verbenol Epoxide (1) with Aldehydes on K10 Clay (General Procedure). A
soln. of aldehyde (0.5 g) in CH2Cl2 (5 ml) was added to a suspension of K10 clay (2.5 g) in CH2Cl2
(10 ml). Then, a soln. of 1 (0.5 g) in CH2Cl2 (5 ml) was added dropwise. The mixture was stirred for
40 min at 208. Then, Et2O (10 ml) and acetone (10 ml) were added. The catalyst was filtered off, and the
solvent was evaporated. The resulting mixture was separated by CC (SiO2 (10 g); hexane/Et2O 100 :0 !
0 :100, acetone).
2.1. Reaction of 1 with Benzaldehyde (2c) on K10 Clay. The products included 3 [23] (0.080 g, 16%),
4 [23] (0.035 g, 7%), 5c (0.134 g, 16%), and a mixture of two isomers 6a/6b (0.052 g, 6%; 3 :1 (1H-NMR)).
(2S,4aR,8R,8aR)-4a,5,8,8a-Tetrahydro-4,4,7-trimethyl-2-phenyl-4H-1,3-benzodioxin-8-ol (5c).
[a]D19 ¼ ꢀ78 (c ¼ 1.64). 1H-NMR (CDCl3)1): 1.27 (s, Me(18)); 1.52 (s, Me(17)); 1.54 (ddd, J(6a,7a) ¼
10.8, J(6a,7e) ¼ 6.0, J(6a,1e) ¼ 2.0, HaꢀC(6)); 1.80 (m, Me(19)); 2.08 (dddq, J(7e,7a) ¼ 17.7, J(7e,6a) ¼
6.0, J(7e,8) ¼ 5.2, J(7e,19) ¼ 1.3, HeꢀC(7)); 2.49 (dddqd, J(7a,7e) ¼ 17.7, J(7a,6a) ¼ 10.8, J(7a,8) ¼ 2.5,
J(7a,19) ¼ 2.5, J(7a,10e) ¼ 1.5, HaꢀC(7)); 3.88 (m, HeꢀC(10)); 4.34 (dd, J(1e,10e) ¼ 2.4, J(1e,6a) ¼ 2.0,
HeꢀC(1)); 5.66 (dm, J(8,7e) ¼ 5.2, HꢀC(8)); 5.79 (s, HꢀC(3)); 7.27 – 7.36 (m, HꢀC(13), HꢀC(14),
HꢀC(15)); 7.47 (dd, J(12,13) ¼ 8.0, J(12,14) ¼ 2.0, HꢀC(12), HꢀC(16)). 13C-NMR (CDCl3)1): 20.48 (q,
C(19)); 22.59 (q, C(17)); 22.90 (t, C(7)); 27.12 (q, C(18)); 33.89 (d, C(6)); 70.27 (d, C(10)); 74.50 (s,
C(5)); 75.03 (d, C(1)); 95.91 (d, C(3)); 125.25 (d, C(8)); 126.25 (d, C(12), C(16)); 128.11 (d, C(13),
C(15)); 128.68 (d, C(14)); 130.59 (s, C(9)); 138.74 (s, C(11)). HR-MS: 274.1555 (Mþ, C17H22O3þ ; calc.
274.1563).
The NMR spectra of isomers 6a and 6b were recorded for 6a/6b 3 :1.
(2S,4S,4aR,8R,8aR)-3,4,4a,5,8,8a-Hexahydro-4,7-dimethyl-2-phenyl-2H-chromene-4,8-diol (6a).
1H-NMR (CDCl3 þ (D6)acetone)1): 1.47 (d, J(17,4a) ¼ 0.7, Me(17)); 1.62 (ddd, J(4e,4a) ¼ 13.4,
J(4e,3a) ¼ 2.7, J(4e,6) ¼ 1.2, HeꢀC(4)); 1.75 (td, J(18,7) ¼ 2.0, J(18,8) ¼ 1.6, Me(18)); 1.85 (br. t,
J(6a,7) ¼ 8.5, HaꢀC(6)); 1.86 (dd, J(4a,4e) ¼ 13.4, J(4a,3a) ¼ 12.0, HaꢀC(4)); 2.14 (dm, J(7,6) ¼ 8.5,
CH2(7)); 3.26 (br. s, HOꢀC(5)); 3.60 (d, J(OH,10) ¼ 6.5, HOꢀC(10)); 3.79 (dd, J(1e,10e) ¼ 2.4,
J(1e,6a) ¼ 2.0, HeꢀC(1)); 3.81 (br. d, J(10e,OH) ¼ 6.5, HeꢀC(10)); 4.40 (dd, J(3a,4a) ¼ 12.0, J(3a,4e) ¼
2.7, HaꢀC(3)); 5.55 (tq, J(8,7) ¼ 3.8, J(8,18) ¼ 1.6, HꢀC(8)); 7.13 – 7.27 (m, HꢀC(12) ꢀ HꢀC(16)).
13C-NMR (CDCl3 þ (D6)acetone)1): 20.86 (q, C(18)); 23.03 (t, C(7)); 27.03 (q, C(17)); 38.66 (d, C(6));
43.53 (t, C(4)); 70.45 (s, C(5)); 70.52 (d, C(10)); 77.61 (d, C(3)); 78.36 (d, C(1)); 124.25 (d, C(8)); 125.97
(d, C(12), C(16)); 127.35 (d, C(14)); 128.27 (d, C(13), C(15)); 131.84 (s, C(9)); 142.87 (s, C(11)). HR-MS:
274.1543 (Mþ, C17H22Oþ3 ; calc. 274.1563).
(2S,4R,4aR,8R,8aR)-3,4,4a,5,8,8a-Hexahydro-4,7-dimethyl-2-phenyl-2H-chromene-4,8-diol (6b).
1H-NMR (CDCl3 þ (D6)acetone)1): 1.18 (s, Me(17)); 1.60 (ddd, J(4e,4a) ¼ 14.0, J(4e,3a) ¼ 3.3,
J(4e,6a) ¼ 1.2, HeꢀC(4)); 1.73 (m, Me(18)); 1.71 – 1.77 (m, HaꢀC(6)); 1.67 (dd, J(4a,4e) ¼ 14.0,
J(4a,3a) ¼ 11.3, HaꢀC(4)); 1.95 (dm, J(7,6a) ¼ 8.5, CH2(7)); 3.30 (br. s, HOꢀC(5)); 3.49 (d,
J(OH,10) ¼ 6.5, HOꢀC(10)); 3.81 (br. d, J(10e,OH) ¼ 6.5, HeꢀC(10)); 4.24 (dd, J(1e,10e) ¼ 2.5,
J(1e,6a) ¼ 2.0, HeꢀC(1)); 4.75 (dd, J(3a,4a) ¼ 11.3, J(3a,4e) ¼ 3.3, HaꢀC(3)); 5.50 (tq, J(8,7) ¼ 3.8,
J(8,18) ¼ 1.6, HꢀC(8)); 7.11 – 7.27 (m, HꢀC(12) – HꢀC(16)). 13C-NMR (CDCl3 þ (D6)acetone)1): 20.95
(q, C(18)); 24.79 (t, C(7)); 28.18 (q, C(17)); 37.96 (d, C(6)); 42.64 (t, C(4)); 70.16 (s, C(5)); 70.50 (d,
C(10)); 75.70 (d, C(1)); 75.82 (d, C(3)); 123.48 (d, C(8)); 125.91 (d, C(12), C(16)); 127.11 (d, C(14));
128.21 (d, C(13), C(15)); 132.50 (s, C(9)); 143.54 (s, C(11)). HR-MS: 274.1543 (Mþ, C17H22O3þ ; calc.
274.1563).
2.2. Reaction of 1 with 4-Hydroxybenzaldehyde (2d) on K10 Clay. The products included 3 (0.168 g,
34%), 4 (0.070 g, 14%), 7 (0.005 g, 1%), and a mixture of two isomers 6c/6d (0.070 g, 8%; (8 :1
(1H-NMR).
1
)
Numbering as indicated in the Formulae.

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The NMR spectra of isomers 6c and 6d were recorded for 6c/6d 8 :1. (2S,4S,4aR,8R,8aR)-
3,4,4a,5,8,8a-Hexahydro-2-(4-hydroxyphenyl)-4,7-dimethyl-2H-chromene-4,8-diol (6c).
1H-NMR (CDCl3 þ (D6)acetone)1): 1.46 (d, J(17,4a) ¼ 0.7, Me(17)); 1.58 (ddd, J(4e,4a) ¼ 13.4,
J(4e,3a) ¼ 2.7, J(4e,6) ¼ 1.2, HeꢀC(4)); 1.75 (td, J(18,7) ¼ 2.0, J(18,8) ¼ 1.7, Me(18)); 1.84 (br. t, J(6a,7) ¼
8.5, HaꢀC(6)); 1.88 (dd, J(4a,4e) ¼ 13.4, J(4a,3a) ¼ 12.0, HaꢀC(4)); 2.15 (dm, J(7,6a) ¼ 8.5, CH2(7)); 3.76
(br. dd, J(10e,OH) ¼ 6.6, J(10e,1e) ¼ 2.4, HeꢀC(10)); 3.78 (dd, J(1e,10e) ¼ 2.4, J(1e,6) ¼ 2.0, HeꢀC(1));
3.80 (d, J(OH,10e) ¼ 6.6, HOꢀC(10)); 4.37 (dd, J(3a,4a) ¼ 12.0, J(3a,4e) ¼ 2.7, HaꢀC(3)); 5.54 (tq,
J(8,7) ¼ 3.8, J(8,18) ¼ 1.7, HꢀC(8)); 6.75 (d, J ¼ 8.6, HꢀC(13), HꢀC(15)); 7.13 (d, J ¼ 8.6, HꢀC(12),
HꢀC(16)); 8.09 (s, HOꢀC(14)). 13C-NMR (CDCl3 þ (D6)acetone)1): 21.19 (q, C(18)); 23.67 (t, C(7));
27.52 (q, C(17)); 39.48 (d, C(6)); 44.31 (t, C(4)); 70.62 (s, C(5)); 71.18 (d, C(10)); 77.93 (d, C(3)); 79.15 (d,
C(1)); 115.58 (d, C(13), C(15)); 124.48 (d, C(8)); 127.93 (d, C(12), C(16)); 132.78 (s, C(9)); 134.90 (s,
C(11)); 157.33 (s, C(14)). HR-MS: 290.1505 (Mþ, C17H22O4þ ; calc. 290.1513).
(2S,4R,4aR,8R,8aR)-3,4,4a,5,8,8a-Hexahydro-2-(4-hydroxyphenyl)-4,7-dimethyl-2H-chromene-4,8-
diol (6d). 1H-NMR (CDCl3 þ (D6)acetone)1): 1.19 (s, Me(17)); 1.55 (ddd, J(4e,4a) ¼ 14.1, J(4e,3a) ¼ 2.9,
J(4e,6a) ¼ 1.4, HeꢀC(4)); 1.72 – 1.74 (m, Me(18)); 1.94 – 2.00 (m, CH2(7)); 4.24 (dd, J(1e,10e) ¼ 2.4,
J(1e,6a) ¼ 2.1, HeꢀC(1)); 4.68 (dd, J(3a,4a) ¼ 11.6, J(3a,4e) ¼ 2.8, HaꢀC(3)); 5.47 – 5.51 (m, HꢀC(8));
6.73 (d, J ¼ 8.5, HꢀC(13), HꢀC(15)); 7.11 (d, J ¼ 8.5, HꢀC(12), HꢀC(16)); 8.05 (s, HOꢀC(14)). Signals
from the other H-atoms were overlapped by those of the major isomer 6c.
2.3. Reaction of 1 with 4-Hydroxy-3-methoxybenzaldehyde (2e) on K10 Clay. The products included
3 (0.140 g, 28%), 4 (0.070 g, 14%), 5e (0.095 g, 10%), and a mixture of two isomers 6e/6f (0.239 g, 25%;
2 :1 (1H-NMR).
(2S,4aR,8R,8aR)-4a,5,8,8a-Tetrahydro-2-(4-hydroxy-3-methoxyphenyl)-4,4,7-trimethyl-4H-1,3-ben-
1
zodioxin-8-ol (5e). [a]1D9 ¼ ꢀ71 (c ¼ 0.60). H-NMR (CDCl3)1): 1.24 (s, Me(18)); 1.48 (ddd, J(6a,7a) ¼
10.8, J(6a,7e) ¼ 6.0, J(6a,1e) ¼ 2.0, HaꢀC(6)); 1.50 (s, Me(17)); 1.79 (br. s, Me(19)); 2.04 (dddq,
J(,7a) ¼ 17.8, J(7e,6a) ¼ 6.0, J(7e,8) ¼ 5.2, J(7e,19) ¼ 1.2, HeꢀC(7)); 2.43 (ddm, J(7a,7e) ¼ 17.8,
J(7a,6a) ¼ 10.8, HaꢀC(7)); 3.82 (br. s, HeꢀC(10)); 3.88 (s, MeO); 4.28 (dd, J(1e,10e) ¼ 2.5, J(1e,6a) ¼
2.0, HeꢀC(1)); 5.61 (br. s, HOꢀC(10)); 5.62 (m, HꢀC(8)); 5.67 (s, HꢀC(3)); 6.82 (d, J(15,16) ¼ 8.0,
HꢀC(15)); 6.91 (br. s, HꢀC(12)); 6.92 (dd, J(16,15) ¼ 8.0, J(16,12) ¼ 2.0, HꢀC(16)). 13C-NMR (CDCl3)1):
20.62 (q, C(19)); 22.81 (q, C(17)); 23.09 (t, C(7)); 27.33 (q, C(18)); 34.07 (d, C(6)); 55.73 (q, C(20)); 70.45
(d, C(10)); 74.50 (s, C(5)); 75.13 (d, C(1)); 95.95 (d, C(3)); 108.76 (d, C(12)); 114.00 (d, C(15)); 119.79 (d,
C(16)); 125.25 (d, C(8)); 130.95, 131.01 (2s, C(9), C(11)); 146.12, 146.16 (2s, C(13), C(14)). HR-MS:
320.1610 (Mþ, C18H24Oþ5 ; calc. 320.1618).
The NMR spectra of isomers 6e and 6f were recorded for 6e/6f 4 :1 and 1:2, resp. (2S,4S,4aR,8-
R,8aR)-3,4,4a,5,8,8a-Hexahydro-2-(4-hydroxy-3-methoxyphenyl)-4,7-dimethyl-2H-chromene-4,8-diol
(6e).
1H-NMR (CDCl3 þ (D6)acetone)1): 1.46 (d, J(17,4a) ¼ 0.7, Me(17)); 1.59 (ddd, J(4e,4a) ¼ 13.3,
J(4e,3a) ¼ 2.7, J(4e,6) ¼ 1.2, HeꢀC(4)); 1.74 (td, J(18,7) ¼ 2.0, J(18,8) ¼ 1.7, Me(18)); 1.83 (br. t, J(6,7) ¼
8.5, HaꢀC(6)); 1.89 (dd, J(4a,4e) ¼ 13.3, J(4a,3a) ¼ 12.0, HaꢀC(4)); 2.14 (dm, J(7,6) ¼ 8.5, CH2(7)); 3.76
(m, HꢀC(1), HꢀC(10)); 3.79 (s, MeO); 4.34 (dd, J(3a,4a) ¼ 12.0, J(3a,4e) ¼ 2.7, HaꢀC(3)); 5.53 (tq,
J(8,7) ¼ 3.8, J(8,18) ¼ 1.7, HꢀC(8)); 6.73 (d, J(15,16) ¼ 8.1, HꢀC(15)); 6.75 (dd, J(16,15) ¼ 8.1, J(16,12) ¼
1.8, HꢀC(16)); 6.85 (d, J(12,16) ¼ 1.8, HꢀC(12)). 13C-NMR (CDCl3 þ (D6)acetone)1): 21.11 (q, C(18));
23.43 (t, C(7)); 27.36 (q, C(17)); 39.19 (d, C(6)); 43.83 (t, C(4)); 56.10 (q, C(19)); 70.57 (s, C(5)); 70.89 (d,
C(10)); 77.94 (d, C(3)); 78.93 (d, C(1)); 110.43 (d, C(12)); 115.12 (d, C(15)); 119.29 (d, C(16)); 124.40 (d,
C(8)); 132.42 (s, C(9)); 135.03 (s, C(11)); 146.31 (s, C(14)); 147.59 (s, C(13)). HR-MS: 320.1608 (Mþ,
C18H24Oþ5 ; calc. 320.1618).
(2S,4R,4aR,8R,8aR)-3,4,4a,5,8,8a-Hexahydro-2-(4-hydroxy-3-methoxyphenyl)-4,7-dimethyl-2H-
chromene-4,8-diol (6f). The NMR spectra of isomer 6f were recorded for 6e/6f 1:2. 1H-NMR (CDCl3 þ
(D6)acetone)1): 1.16 (s, Me(17)); 1.55 (ddd, J(4e,4a) ¼ 14.0, J(4e,3a) ¼ 3.0, J(4e,6) ¼ 1.3, HeꢀC(4)); 1.66
(dd, J(4a,4e) ¼ 14.0, J(4a,3a) ¼ 11.5, HaꢀC(4)); 1.68 (br. t, J(6a,7) ¼ 8.5, HaꢀC(6)); 1.74 (td, J(18,7) ¼ 2.0,
J(18,8) ¼ 1.7, Me(18)); 1.93 (dm, J(7,6) ¼ 8.5, CH2(7)); 3.77 (br. s, HeꢀC(10)); 3.78 (s, MeO); 4.18 (dd,
J(1e,10e) ¼ 2.5, J(1e,6a) ¼ 2.0, HeꢀC(1)); 4.64 (dd, J(3a,4a) ¼ 11.5, J(3a,4e) ¼ 3.0, HaꢀC(3)); 5.47 (tq,
J(8,7) ¼ 3.8, J(8,18) ¼ 1.7, HꢀC(8)); 6.59 (br. s, HOꢀC(14)); 6.69 – 6.72 (m, HꢀC(15), HꢀC(16)); 6.76
(br. s, HꢀC(12)). 13C-NMR (CDCl3 þ (D6)acetone)1): 20.97 (q, C(18)); 24.76 (t, C(7)); 28.24 (q, C(17));

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37.99 (d, C(6)); 42.42 (t, C(4)); 55.81 (q, C(19)); 70.27 (s, C(5)); 70.47 (d, C(10)); 75.71 (d, C(1)); 75.80 (d,
C(3)); 114.50 (d, C(15)); 118.81 (d, C(16)); 123.44 (d, C(8)); 132.48 (s, C(9)); 134.98 (s, C(11)); 109.50 (d,
C(12)); 145.36 (s, C(14)); 146.81 (s, C(13)). HR-MS: 320.1608 (Mþ, C18H24O5þ ; calc. 320.1618).
2.4. Reaction of 1 with 3-Hydroxy-4-methoxybenzaldehyde (2f) on K10 Clay. The products included 4
(0.075 g, 15%), 7 (0.025 g, 5%), 5f (0.048 g, 5%), and a mixture of two isomers 6g/6h (0.266 g, 28%; 1:1
(1H-NMR).
(2S,4aR,8R,8aR)-4a,5,8,8a-Tetrahydro-2-(3-hydroxy-4-methoxyphenyl)-4,4,7-trimethyl-4H-1,3-ben-
1
zodioxin-8-ol (5f). [a]1D9 ¼ ꢀ46 (c ¼ 0.73). H-NMR (CDCl3)1): 1.23 (s, Me(18)); 1.49 (s, Me(17)); 1.50
(ddd, J(6a,7a) ¼ 10.8, J(6a,7e) ¼ 6.1, J(6a,1e) ¼ 2.0, HaꢀC(6)); 1.78 (br. s, Me(19)); 2.04 (dddq, J(7e,6a) ¼
17.7, J(7e,6a) ¼ 6.1, J(7e,8) ¼ 5.2, J(7e,19) ¼ 1.2, HeꢀC(7)); 2.45 (ddm, J(7a,7e) ¼ 17.7, J(7a,6a) ¼ 10.8,
HaꢀC(7)); 3.83 (s, MeO); 3.86 (m, HeꢀC(10)); 4.31 (dd, J(1e,10e) ¼ 2.5, J(1e,6a) ¼ 2.0, HeꢀC(1)); 5.63
(dm, J(8,7e) ¼ 5.2, HꢀC(8)); 5.69 (s, HꢀC(3)), 6.78 (d, J(15,16) ¼ 8.2, HꢀC(15); 6.92 (dd, J(16,15) ¼ 8.2,
J(16,12) ¼ 2.0, HꢀC(16)); 7.04 (d, J(12,16) ¼ 2.0, HꢀC(12)). 13C-NMR (CDCl3)1): 20.48 (q, C(19)); 22.67
(q, C(17)); 22.99 (t, C(7)); 27.20 (q, C(18)); 33.97 (d, C(6)); 55.93 (q, C(20)); 70.48 (d, C(10)); 74.50 (s,
C(5)); 74.96 (d, C(1)); 95.71 (d, C(3)); 110.24 (d, C(15)); 112.73 (d, C(12)); 118.21 (d, C(16)); 125.41 (d,
C(8)); 130.69 (s, C(9)); 132.48 (s, C(11)); 145.46 (s, C(13)); 146.97 (s, C(14)). HR-MS: 320.1616 (Mþ,
C18H24Oþ5 ; calc. 320.1618).
The NMR spectra of isomers 6g and 6h were recorded for 6g/6h 2 :1. (2S,4S,4aR,8R,8aR)-
3,4,4a,5,8,8a-Hexahydro-2-(3-hydroxy-4-methoxyphenyl)-4,7-dimethyl-2H-chromene-4,8-diol (6g).
1H-NMR (CDCl3)1): 1.49 (d, J(17,4a) ¼ 0.8, Me(17)); 1.63 (ddd, J(4e,4a) ¼ 13.4, J(4e,3a) ¼ 2.7,
J(4e,6) ¼ 1.2, HeꢀC(4)); 1.79 (m, Me(18)); 1.77 – 1.82 (m, HaꢀC(6)); 1.88 (dd, J(4a,4e) ¼ 13.4, J(4a,3a) ¼
12.0, HaꢀC(4)); 2.15 (dm, J(7,6) ¼ 8.5, CH2(7)); 3.77 (dd, J(1e,10e) ¼ 2.4, J(1e,6a) ¼ 2.0, HeꢀC(1)); 3.83
(s, MeO); 3.89 (br. d, J(10e,1e) ¼ 2.4, HeꢀC(10)); 4.32 (dd, J(3a,4a) ¼ 12.0, J(3a,4e) ¼ 2.7, HaꢀC(3)); 5.62
(tq, J(8,7) ¼ 3.8, J(8,18) ¼ 1.5, HꢀC(8)); 6.73 – 6.79 (m, HꢀC(15), HꢀC(16)); 6.88 – 6.91 (m, HꢀC(12)).
13C-NMR (CDCl3)1): 20.64 (q, C(18)); 22.66 (t, C(7)); 26.99 (q, C(17)); 38.37 (d, C(6)); 43.13 (t, C(4));
55.93 (q, C(19)); 70.59 (d, C(10)); 71.12 (s, C(5)); 77.20 (d, C(3)); 77.60 (d, C(1)); 110.45 (d, C(15));
112.45 (d, C(12)); 117.52 (d, C(16)); 124.61 (d, C(8)); 131.37 (s, C(9)); 135.34 (s, C(11)); 145.51 (s, C(13));
146.03 (s, C(14)). HR-MS: 320.1615 (Mþ, C18H24O5þ ; calc. 320.1618).
(2S,4R,4aR,8R,8aR)-3,4,4a,5,8,8a-Hexahydro-2-(3-hydroxy-4-methoxyphenyl)-4,7-dimethyl-2H-
1
chromene-4,8-diol (6h). H-NMR (CDCl3)1): 1.21 (s, Me(17)); 1.59 (ddd, J(4e,4a) ¼ 14.2, J(4e,3a) ¼ 2.9,
J(4e,6a) ¼ 1.4, HeꢀC(4)); 1.67 (br. t, J(6a,7) ¼ 8.7, HaꢀC(6)); 1.74 (dd, J(4a,4e) ¼ 14.2, J(4a,3a) ¼ 11.7,
HaꢀC(4)); 1.79 (m, Me(18)); 1.97 – 2.02 (m, CH2(7)); 3.82 (s, MeO); 3.91 (br. s, HeꢀC(10)); 4.21 (dd,
J(1e,10e) ¼ 2.5, J(1e,6a) ¼ 2.0, HeꢀC(1)); 4.68 (dd, J(3a,4a) ¼ 11.7, J(3a,4e) ¼ 2.9, HaꢀC(3)); 5.56 (m,
HꢀC(8)), 5.67 (br. s, HOꢀC(13)); 6.73 – 6.79 (m, HꢀC(15), HꢀC(16)); 6.88 – 6.91 (m, HꢀC(12)).
13C-NMR (CDCl3)1): 20.74 (q, C(18)); 24.58 (t, C(7)); 28.33 (q, C(17)); 38.10 (d, C(6)); 42.08 (t, C(4));
55.93 (q, C(19)); 70.57 (d, C(10)); 70.85 (s, C(5)); 75.11 (d, C(1)); 75.41 (d, C(3)); 110.45 (d, C(15));
112.40 (d, C(12)); 117.57 (d, C(16)); 123.97 (d, C(8)); 131.87 (s, C(9)); 136.03 (s, C(11)); 145.48 (s, C(13));
145.87 (s, C(14)). HR-MS: 320.1615 (Mþ, C18H24O5þ ; calc. 320.1618).
2.5. Reaction of 1 with 3,4,5-Trimethoxybenzaldehyde (2g) on K10 Clay. The products included 3 (0.
050 g, 10%), 5 (0.060 g, 12%), 7 (0.036 g, 7%), 5g (0.063 g, 6%), a mixture of two diasteroisomers 6i/6k
(0.267 g, 25%; 3 :1 (1H-NMR), and compound 8b (0.077 g, 5%).
(2S,4aR,8R,8aR)-4a,5,8,8a-Tetrahydro-4,4,7-trimethyl-2-(3,4,5-trimethoxyphenyl)-4H-1,3-benzo-
dioxin-8-ol (5g). [a]1D9 ¼ ꢀ69 (c ¼ 0.88). 1H-NMR (CDCl3)1): 1.26 (s, Me(18)); 1.50 (s, Me(17)); 1.51
(ddd, J(6a,7a) ¼ 10.8, J(6a,7e) ¼ 6.0, J(6a,1e) ¼ 1.9, HaꢀC(6)); 1.78 (m, Me(19)); 2.07 (dddq, J(7e,7a) ¼
17.7, J(7e,6a) ¼ 6.0, J(7e,8) ¼ 5.4, J(7e,19) ¼ 1.3, HeꢀC(7)); 2.44 (ddm, J(7a,7e) ¼ 17.7, J(7a,6a) ¼ 10.8,
HaꢀC(7)); 3.76 (s, MeO(21)); 3.84 (s, MeO(20), MeO(22)); 3.88 (br. s, HeꢀC(10)); 4.33 (dd, J(1e,10e) ¼
2.5, J(1e,6a) ¼ 1.9, HeꢀC(1)); 5.63 (dm, J(8,7e) ¼ 5.4, HꢀC(8)); 5.70 (s, HaꢀC(3)); 6.68 (s, HꢀC(12),
HꢀC(16)). 13C-NMR (CDCl3)1): 20.43 (q, C(19)); 22.66 (q, C(17)); 22.95 (t, C(7)); 27.15 (q, C(18)); 34.01
(d, C(6)); 55.93 (q, C(20), C(22)); 60.48 (q, C(21)); 70.36 (d, C(10)); 74.71 (s, C(5)); 75.25 (d, C(1)); 95.99
(d, C(3)); 103.52 (d, C(12); C(16)); 125.21 (d, C(8)); 130.75 (s, C(9)); 134.32 (s, C(11), C(14)); 153.10 (s,
C(13), C(15)). HR-MS: 364.1883 (Mþ, C20H28O6þ ; calc. 364.1880).
The NMR spectra of isomers 6i and 6k were recorded for 6i/6k 1:1.4. (2S,4S,4aR,8R,8aR)-
3,4,4a,5,8,8a-Hexahydro-4,7-dimethyl-2-(3,4,5-trimethoxyphenyl)-2H-chromene-4,8-diol (6i).

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1H-NMR (CDCl3)1): 1.51 (d, J(17,4a) ¼ 0.7, Me(17)); 1.67 (dm, J(4e,4a) ¼ 13.3, HeꢀC(4)); 1.80 (m,
Me(18)); 1.82 (br. t, J(6a,7) ¼ 8.5, HaꢀC(6)); 1.95 (dd, J(4a,4e) ¼ 13.3, J(4a,3a) ¼ 12.0, HaꢀC(4)); 2.14 –
2.20 (m, 2 H(7)); 3.78 (s, Me(20)O); 3.81 (m, HeꢀC(1)); 3.83 (s, Me(19)O, Me(21)O); 3.92 (br. s,
HeꢀC(10)); 4.35 (dd, J(3a,4a) ¼ 12.0, J(3a,4e) ¼ 2.7, HaꢀC(3)); 5.64 (tm, J(8,7) ¼ 3.9, HꢀC(8)); 6.52 (s,
HꢀC(12), HꢀC(16)). 13C-NMR (CDCl3)1): 20.62 (q, C(18)); 22.65 (t, C(7)); 27.08 (q, C(17)); 38.41 (d,
C(6)); 42.63 (t, C(4)); 60.60 (q, C(20)); 70.52 (d, C(10)); 71.05 (s, C(5)); 77.76 (d, C(3)); 77.83 (d, C(1));
103.31 (d, C(12), C(16)); 124.55 (d, C(8)); 131.37 (s, C(9)); 137.24 (s, C(11)); 137.54 (s, C(14)); 153.13 (s,
C(13), C(15)); 56.03 (q, C(19), C(21)). HR-MS: 364.1881 (Mþ, C20H28O6þ ; calc. 364.1880).
(2S,4R,4aR,8R,8aR)-3,4,4a,5,8,8a-Hexahydro-4,7-dimethyl-2-(3,4,5-trimethoxyphenyl)-2H-chro-
mene-4,8-diol (6k). 1H-NMR (CDCl3)1): 1.24 (s, Me(17)); 1.64 (ddd, J(4e,4a) ¼ 14.2, J(4e,3a) ¼ 2.8,
J(4e,6a) ¼ 1.3, HeꢀC(4)); 1.68 (br. t, J(6a,7) ¼ 8.5, HaꢀC(6)); 1.77 (dd, J(4a,4e) ¼ 14.2, J(4a,3a) ¼ 11.6,
HaꢀC(4)); 1.80 (m, Me(18)); 1.98 – 2.04 (m, CH2(7)); 3.77 (s, Me(20)O); 3.82 (s, Me(19)O, Me(21)O);
3.94 (br. s, HeꢀC(10)); 4.25 (dd, J(1e,10e) ¼ 2.5, J(1e,6a) ¼ 2.0, HeꢀC(1)); 4.71 (dd, J(3a,4a) ¼ 11.6,
J(3a,4e) ¼ 2.8, HaꢀC(3)); 5.58 (m, HꢀC(8)); 6.52 (s, HꢀC(12), H(16)). 13C-NMR (CDCl3)1): 20.72 (q,
C(18)); 24.56 (t, C(7)); 28.34 (q, C(17)); 38.17 (d, C(6)); 41.88 (t, C(4)); 60.60 (q, C(20)); 70.51 (d, C(10));
70.81 (s, C(5)); 75.35 (d, C(1)); 76.06 (d, C(3)); 103.15 (d, C(12), C(16)); 123.88 (d, C(8)); 131.87 (s,
C(9)); 137.30 (s, C(14)); 138.07 (s, C(11)); 153.10 (s, C(13), C(15)); 56.02 (q, C(19), C(21)). HR-MS:
364.1881 (Mþ, C20H28Oþ6 ; calc. 364.1880).
(2R,4S,4aR,6S,7R,8aR,9S)-Hexahydro-4,7-dimethyl-2,9-bis(3,4,5-trimethoxyphenyl)-2H-4,6-(epoxy-
methano)chromen-8(5H)-one (8b). [a]D19 ¼ ꢀ60 (c ¼ 0.67). 1H-NMR (CDCl3)1): 1.12 (d, J(18,9) ¼ 7.5,
Me(18)); 1.43 (s, Me(17)); 1.70 (dd, J(4a,4e) ¼ 13.8, J(4a,3a) ¼ 12.0, HaꢀC(4)); 1.86 (m, all J ꢂ 3.3,
HeꢀC(8)); 2.04 (dd, J(4e,4a) ¼ 13.8, J(4e,3a) ¼ 2.5, HeꢀC(4)); 2.28 (ddd, J(7a,7e) ¼ 14.2, J(7a,6e) ¼ 3.3,
J(7a,8e) ¼ 3.1, HꢀC(7)); 2.34 (dddd, J(6e,1a) ¼ 5.8, J(6e,7a) ¼ 3.3, J(6e,7e) ¼ 3.1, J(6e,8e) ¼ 0.6,
HeꢀC(6)); 2.43 (dddd, J(7e,7a) ¼ 14.2, J(7e,8e) ¼ 3.3, J(7e,6e) ¼ 3.1, J(7e,9e) ¼ 1.7, HeꢀC(7)); 2.57
(qdd, J(9e,18) ¼ 7.5, J(9e,8e) ¼ 2.0, J(9e,7e) ¼ 1.7, HeꢀC(9)); 3.79, 3.80 (2s, Me(20)O, Me(30)O); 3.85,
3.86 (2s, Me(19)O, Me(21)O, Me(29)O, Me(31)O); 4.45 (d, J(1a,6e) ¼ 5.8, HaꢀC(1)); 5.02 (d, J(22,8e) ¼
2.0, HꢀC(22)); 5.07 (dd, J(3a,4a) ¼ 12.0, J(3a,4e) ¼ 2.5, HaꢀC(3)); 6.48 (s, HꢀC(24), HꢀC(28)), 6.63 (s,
HꢀC(12), HꢀC(16)). 13C-NMR (CDCl3)1): 17.48 (q, C(18)); 21.97 (q, C(17)); 22.34 (t, C(7)); 41.18 (d,
C(6)); 42.34 (d, C(8)); 43.47 (d, C(9)); 46.20 (t, C(4)); 55.99, 56.01 (2q, C(19), C(21), C(29), C(31));
60.65 (q, C(20), C(30)); 69.32 (d, C(3)); 73.04 (s, C(5)); 76.00 (d, C(22)); 76.16 (d, C(1)); 102.88 (d,
C(12), C(16)); 137.05 (s, C(26)); 137.19 (s, C(14)); 137.70 (s, C(11)); 153.06 (s, C(13), C(15)); 135.58 (s,
C(23)); 103.21 (d, C(24), C(28)); 153.01 (s, C(25), C(27)); 209.55 (s, C(10)). HR-MS: 542.2508 (Mþ,
C30H38Oþ9 ; calc. 542.2510).
3. Reaction of Diol 3 with Aldehydes on K10 Clay. 3.1. Reaction of Diol 3 with 4-Hydroxy-3-
methoxybenzaldehyde (2e) on K10 Clay. A soln. of 3 (0.20 g) and 2e (0.20 g) in CH2Cl2 (5 ml) was added
to a suspension of K10 clay (0.80 g) in CH2Cl2 (10 ml). The solvent was evaporated, and the mixture was
maintained at r.t. for 7 d. Then, Et2O (5 ml) was added. The catalyst was filtered off, and the solvent was
evaporated. The resulting mixture was separated by CC (SiO2 (10 g); hexane/Et2O 100 :0 ! 0 :100,
acetone) to afford 3 (0.100 g, conversion 50%), and mixture of isomers 6e/6f (3 :1 (1H-NMR); 0.094 g,
50%); yield based on converted 3.
3.2. Reaction of Diol 3 with 3-Hydroxy-4-methoxybenzaldehyde (2f) on K10 Clay. A soln. of 3
(0.60 g) and 2f (0.70 g) in CH2Cl2 (15 ml) was added to a suspension of K10 clay (3.0 g) in CH2Cl2
(10 ml). The solvent was evaporated, and the mixture was maintained at r.t. for 4 d. Then, Et2O (20 ml)
and AcOEt (20 ml) were added. The catalyst was filtered off, and the solvent evaporated. The resulting
mixture was separated by CC (SiO2 (10 g); hexane/AcOEt 100 :0 ! 0 :100, acetone) to afford 5f (0.058 g,
5%), mixture of isomers 6g/6h (5 :1 (1H-NMR); 0.336 g, 29%) and 8a (0.126 g, 8%).
(2R,4S,4aR,6S,7R,8aR,9S)-Hexahydro-2,9-bis(3-hydroxy-4-methoxyphenyl)-4,7-dimethyl-2H-4,6-
(epoxymethano)chromen-8(5H)-one (8a). [a]1D9 ¼ ꢀ74 (c ¼ 0.76). 1H-NMR (CDCl3)1): 1.10 (d, J(18,9) ¼
7.5, Me(18)); 1.46 (s, Me(17)); 1.88 (m, all J ꢂ 3.1, HeꢀC(8)); 1.91 (dd, J(4e,4a) ¼ 15.0, J(4e,3a) ¼ 2.6,
HeꢀC(4)); 2.21 (dd, J(4a,4e) ¼ 15.0, J(4a,3a) ¼ 13.2, HaꢀC(4)); 2.38 (dd, J(7,6e) ¼ 3.1, J(7,8e) ¼ 3.1,
CH2(7)); 2.52 (br. q, J(9e,18) ¼ 7.5, HeꢀC(9)); 2.57 (dtd, J(6e,1a) ¼ 5.3, J(6e,7) ¼ 3.1, J(6e,8e) ¼ 1.0,
HeꢀC(6)); 3.85, 3.87 (2s, 2 MeO); 4.52 (dd, J(1a, 6e) ¼ 5.3, J(1a,9e) ¼ 0.6, HaꢀC(1)); 4.68 (dd, J(3a,4a) ¼
13.2, J(3a,4e) ¼ 2.6, HaꢀC(3)); 4.74 (d, J(20,8e) ¼ 1.6, HꢀC(20)); 5.57, 5.59 (2s, 2 OH); 6.74 – 6.82 (m,

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Helvetica Chimica Acta – Vol. 94 (2011)
HꢀC(22), HꢀC(25), HꢀC(26)); 6.84 (d, J(15,16) ¼ 8.2, HꢀC(15)); 7.11 (d, J(12,16) ¼ 2.1, HꢀC(12)); 7.15
(dd, J(16,15) ¼ 8.2, J(16,12) ¼ 2.1, HꢀC(16)). 13C-NMR (CDCl3)1): 17.71 (q, C(18)); 23.16 (q, C(17));
24.35 (t, C(7)); 39.02 (d, C(6)); 42.50 (d, C(9)); 43.51 (d, C(8)); 48.27 (t, C(4)); 55.89 (q, C(19), C(27));
71.82 (d, C(3)); 72.93 (s, C(5)); 75.02 (d, C(20)); 76.39 (d, C(1)); 110.48 (d, C(25)); 110.61 (d, C(15));
112.05 (d, C(22)); 113.07 (d, C(12)); 117.40 (d, C(26)); 118.22 (d, C(16)); 133.58 (s, C(21)); 135.36 (s,
C(11)); 145.25 (s, C(23)); 145.33 (s, C(13)); 145.55 (s, C(24)); 146.11 (s, C(14)); 212.06 (s, C(10)). HR-
MS: 454.1982 (Mþ, C26H30Oþ7 ; calc. 454.1986).
3.3. Reaction of Diol 3 with 3,4,5-Trimethoxybenzaldehyde (2g) on K10 Clay. A soln. of 3 (0.50 g) in
CH2Cl2 (15 ml) and aldehyde 2g (0.60 g) was added to a suspension of K10 clay (2.5 g) in CH2Cl2 (10 ml).
The solvent was evaporated, and the mixture was maintained at r.t. for 7 d. Then, acetone (20 ml) and
AcOEt (20 ml) were added. The catalyst was filtered off, and the solvent was evaporated. The resulting
mixture was separated by CC (SiO2 (17 g); hexane/Et2O 100 :0 ! 0 :100, acetone) to afford 5g (0.034 g,
3%), mixture of isomers 6i/6k (3 :1 (1H-NMR); 0.421 g, 39%) and 8b (0.149 g, 9%).
Axial or equatorial positions of H-atoms in all compounds were determined from vicinal coupling
and long-range coupling constants of observable atoms. Axial position of Me(17) in compounds 6a, 6c,
6e, 6g, and 6k was assigned due to observation of long-rang spin-spin coupling constant of this group with
HaꢀC(4) (J 0.7 – 0.8 Hz).
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Received July 16, 2010