Naphthopyrans and their C4 alcohols by cyclization of substituted naphthalenes using potassium t-butoxide in dimethylformamide. generality and stereochemical, including conformational, effects

Article abstract of DOI:10.1071/CH07301

The generality of the high-yielding, stereoselective cyclization of 2-allyl-3-(1?-hydroxyethyl)-1,4-dimethoxynaphthalene 1 to afford trans-3,4-dihydro-5,10-dimethoxy-1,3-dimethylnaphtho[2,3-c]pyran 2 is investigated by replacing each of the methoxy groups in the substrate by an ethyl substituent and subjecting these to cyclization reaction conditions identical to those originally reported. For shorter reaction times with potassium tert-butoxide in dimethylformamide under nitrogen, the derived 1-ethyl-, 4-ethyl-, and 1,4-diethylnaphthalenes all cyclize to the trans-1,3-dimethyl compounds, whereas longer times yield increasing proportions of the corresponding cis-isomers. Under air, the epimeric C4 alcohols rel-(1R,3R,4S)-3,4-dihydro-5-ethyl-4-hydroxy-10-methoxy-1,3-dimethylnaphtho[2, 3-c]pyran 50 and its rel-(1R,3R,4R) isomer 51 are also isolated from 2-allyl-1-ethyl-3-(1?-hydroxyethyl)-4-methoxynaphthalene 11. The half-chair conformation of pyran 50 is inverted relative to that of its C4 epimer 51. CSIRO 2007.

Full text of DOI:10.1071/CH07301

Full Paper
CSIRO PUBLISHING
Aust. J. Chem. 2007, 60, 934–945
www.publish.csiro.au/journals/ajc
Naphthopyrans and their C4 Alcohols by Cyclization
of Substituted Naphthalenes using Potassium t-Butoxide
in Dimethylformamide. Generality and Stereochemical,
including Conformational, Effects
Robin G. F. Giles,A,C Ivan R. Green,B,C Wendell P. Swigelaar,B
and C. Peter TaylorC
ADepartment of Chemistry, Murdoch University, Murdoch WA 6150, Australia.
BDepartment of Chemistry, University of the Western Cape, Bellville, 7530, South Africa.
CCorresponding authors. Email: r.giles@murdoch.edu.au; igreen@uwc.ac.za
The generality of the high-yielding, stereoselective cyclization of 2-allyl-3-(1ꢀ-hydroxyethyl)-1,4-dimethoxynaphthalene
1 to afford trans-3,4-dihydro-5,10-dimethoxy-1,3-dimethylnaphtho[2,3-c]pyran 2 is investigated by replacing each of the
methoxy groups in the substrate by an ethyl substituent and subjecting these to cyclization reaction conditions identical to
those originally reported. For shorter reaction times with potassium tert-butoxide in dimethylformamide under nitrogen,
the derived 1-ethyl-, 4-ethyl-, and 1,4-diethylnaphthalenes all cyclize to the trans-1,3-dimethyl compounds, whereas longer
times yield increasing proportions of the corresponding cis-isomers. Under air, the epimeric C4 alcohols rel-(1R,3R,4S)-
3,4-dihydro-5-ethyl-4-hydroxy-10-methoxy-1,3-dimethylnaphtho[2,3-c]pyran 50 and its rel-(1R,3R,4R) isomer 51 are
also isolated from 2-allyl-1-ethyl-3-(1ꢀ-hydroxyethyl)-4-methoxynaphthalene 11. The half-chair conformation of pyran
50 is inverted relative to that of its C4 epimer 51.
Manuscript received: 24 August 2007.
Final version: 27 September 2007.
Introduction
smooth transformations. In the series of ortho-pentenylbenzyl
alcohols 3–6 only the dimethoxy compound 3 cyclized smoothly
(in a yield of 85%) to afford benzopyran 7 using butoxide as
described above. The ortho-methoxybenzyl alcohol 4, in which
there is only one flanking methoxy group, provided a mixture
from which the product 8 was formed in a yield of only 29%
whereas neither 5, the regioisomer of 4, nor the analogue 6 with-
out any methoxy substituent, cyclized at all under the standard
conditions. This suggested that the ring-closure was facilitated
through steric compression forcing the reacting centres together,
although the involvement of electronic factors arising from the
methoxy substituents at C1 and C4 could not be excluded. Lit-
erature precedents[12–14] exist for the formation of ethers, under
basic conditions, from the reaction of an alcohol function with
an unactivated double bond when the two are held in close
proximity.
The present paper describes efforts to establish or exclude,
in these cyclizations, any involvement of electronic factors aris-
ing from the two methoxy groups through replacing either one or
both of these with an ethyl substituent, as such substitution would
minimize spatial changes in the substrates.The three compounds
9–11, analogues of the dimethyl ether 1, were therefore synthe-
sized and their reactions with butoxide in dimethylformamide at
60◦C were investigated with respect to both substrate cyclization
and product stereochemistry.Three additional substrates for ring
closure, 12–14, were also assembled. The first two of these were
the hydroxymethyl analogues of 9 and 10 in which the replace-
ment of the benzylic methyl with hydrogen might be expected
We have previously reported the base-induced cyclization of 2-
allyl-3-(1ꢀ-hydroxyethyl)-1,4-dimethoxynaphthalenes to afford
naphthopyrans in reactions that are unusual in that they pro-
ceed rapidly in high yield and with complete stereoselectivity
and also, prima facie, involve the intramolecular nucleo-
philic addition of alkoxide to a double bond. Thus, under
nitrogen at 60◦C, the substrate 1 affords solely the trans-
1,3-dimethylnaphthopyran 2 in 5 min in virtually quantitative
yield under the influence of potassium t-butoxide in dimethyl-
formamide (Scheme 1).[1] Prolonging the reaction time produces
an increasing proportion of the corresponding cis-isomer. There
is little stereoselectivity in the analogous Lewis acid-catalyzed
reactions.[2,3] As a consequence, these base-promoted cycliza-
tions have found use in the stereoselective synthesis of natural
products,[4] their derivatives,[5] and analogues.[6–10]
We have also identified[11] the structural features in the cor-
responding benzenoid analogues required for these remarkably
MeO
MeO
OH
O
KOtBu, DMF
1
60°C, N2, 5 min
MeO
MeO
1
2
Scheme 1.
© CSIRO 2007
10.1071/CH07301
0004-9425/07/120934

Naphthopyrans and their C4 Alcohols
935
to reduce crowding. The less sterically congested compound 14
lacking the ethyl substituent in 12 was also made.
ortho-acrylyl and hydroxymethyl groups, which would lead
to the isomeric hemiacetal that would then undergo further
oxidative loss of two carbons to yield the observed γ-lactones.
Although this mechanism would lead to 28 and the regioisomer
of 27, the almost identical carbonyl absorptions for the two
analogous γ-lactones suggest virtually no difference in conju-
gation with the carbonyl and, therefore, that ethyl is peri- to
each carbonyl, as in the lactones 27 and 28. Thus, on the avail-
able evidence, a choice between 27 and its regioisomer was not
made. As this compound was an unwanted minor by-product, it
was not investigated further.
The starting material chosen for the target alcohol 11 was
the known[17] allyl ether 32. Claisen rearrangement formed
the intermediate tetrasubstituted naphthol 33 that was trans-
formed smoothly into the triflate 34. A Stille coupling was
performed on this compound using tetraethyltin in the presence
of bistriphenylphosphinedichloropalladium(ii) whereupon the
ethylated product 35 was obtained in a yield of 75%. Reduction
of the ketone group with lithium aluminium hydride afforded
the required alcohol 11 in high yield. The overall yield of this
alcohol in the five steps from the allyl ether 32 was 57%.
The alcohol 14 was obtained from the benzaldehyde-derived
Stobbe product 18. This was readily transformed through the
sequence 19,[18] 20, 36, 37, and 14 as for the conversion of the
Stobbe-derived naphthalene 15 into 12.
Results and Discussion
Syntheses of the Substrates 9–14
A convenient synthesis of naphthalene 9 was achieved starting
with naphthalene 15 obtained[15] from propiophenone using a
Stobbe reaction. Selective hydrolysis of the acetate ester and
allylation of the intermediate naphthol 16 afforded the ether
17. Claisen rearrangement of this ether gave the tetrasubstituted
naphthol 21 as shown by the upfield shift of the allyl methylene
protons in the 1H NMR spectrum, as well as the absence of the
aromatic singlet present in its precursors 15–17. This unstable
naphthol 21 was O-methylated immediately to form the ether 22
and the ester function was reduced to give the alcohol 12. Man-
ganese dioxide oxidation of this alcohol provided the required
aldehyde 23 in a yield of 63% and with an infrared carbonyl
absorption of 1694 cm−1. Treatment of the aldehyde 23 with
methylmagnesium iodide gave the required alcohol 9. Its overall
yield from the Stobbe product 15 was 27% in seven steps.
The manganese dioxide oxidation of the alcohol 12 also pro-
duced a minor by-product that showed an infrared carbonyl
absorption at 1746 cm−1 and, aside from the expected ethyl and
1
methoxy resonances in the H NMR spectrum, the only non-
aromatic proton absorption was a sharp two-proton singlet at
δ 5.38 with a corresponding signal at δ 68.5 in the 13C NMR
spectrum. This led to its formulation as either the γ-lactone 27
or its regioisomer in which the ethyl and methoxy substituents
were reversed, and this was obtained in a yield of 17%.
Cyclizations of the Substrates 9–14
The alcohol 9 was treated under nitrogen with potassium tert-
butoxide (4 equivalents) in dry dimethylformamide at 60◦C for
30 min, whereupon the trans-1,3-dimethylnaphthopyran 38 was
obtained as a single product in a yield of 69%. Longer reac-
tion times produced increasing quantities of the cis-isomer 41,
as can be seen from the data provided in Table 1 (entries 1–
4). The two isomers were readily distinguished by the chemical
shifts of their protons H3 as it is known[1] that for such benzo-
and naphthopyrans, the values for the trans-isomers are at lower
field (normally δ 3.9–4.3) than for the corresponding cis-isomers
(normally δ 3.5–3.8). For the compounds 38 and 41, these values
were δ 4.26 and 3.65, respectively.
The tetrasubstituted naphthol 21 was also used for the assem-
bly of the required diethyl target 10. Freshly prepared material
obtained through pyrolysis of the allyl ether 17 was con-
verted into the triflate 24 and this was followed by a smooth
Stille reaction[16] with tetraethyltin in the presence of bistri-
phenylphosphinedichloropalladium(ii)thatprovidedthediethyl-
naphthyl ester derivative 25 in a yield of 96%. This ester was
reduced to provide the alcohol 13, which was in turn con-
verted using manganese dioxide into the aldehyde 26 and the
γ-lactone 28 in yields of 65 and 18%, respectively. The alde-
hyde 26 was transformed into the required alcohol 10 using
methylmagnesium iodide in a reaction that also provided the
vinylisonaphthofuran 29, in yields of 63 and 20%, respectively.
Furan 29 could arise (Scheme 2) through the abstraction of an
allylic methylene proton from 26 by the Grignard reagent to give
the highly resonance-stabilized enolate anion 30 that cyclized to
the naphthofuran anion 31. The alcohol 10 was formed in an
overall yield of 22% in five steps from the allyl ether 17, or in
17% in seven steps from the Stobbe product 15.
For the γ-lactone 28, only one structure is possible in view
of the symmetry present through both substituents at C4 and
C9 being ethyl groups, whereas for its analogue 27 described
above such symmetry is absent, leading, therefore, to two pos-
sible regioisomers. In the formation of these γ-lactones from
their precursor alcohols 12 and 13, either one or other of the
adjacent hydroxymethyl or allyl substituents on the naphtha-
lene ring might undergo oxidation of the respective benzylic
groups, the former to a carboxyl or the latter to an acrylyl
(prop-2-enoyl)group, fromwhichtheobservedγ-lactoneswould
arise. Although it would be premature to hypothesize on a
mechanism for the subsequent cyclization of any derived ortho-
allylnaphthoic acid intermediate, it could be speculated that one
possible mechanism involved the cyclization of the alternative
When the diethyl alcohol 10 was treated with t-butoxide in
dimethylformamide at 60◦C for 30 min (entry 5), the trans- and
cis-naphthopyrans 39 and 42 were isolated in yields of 43 and
1
11%, and H NMR spectroscopic H3 resonances appeared at
δ 4.35 and 3.70, respectively. In addition, under these condi-
tions, the double bond-conjugated alcohol 45 was isolated in
37% yield, as an inseparable 1:1 mixture of geometric Z- and
E-isomers, as well as the phenanthrene 46 in a yield of 6%.
Aside from that seen in the 1H NMR spectrum, additional evi-
dence for 45 as a pair of geometric isomers was observed in
the 13C NMR spectrum in which all seven sp3-hybridized car-
bon atoms appeared as pairs of signals. The related spectrum for
phenanthrene 46 showed only five sp3 carbons.
The observation of the mixture of geometric isomers 45 sug-
gested their intermediacy in the conversion of compound 10
into the naphthopyrans 39 and thence 42. This was supported
by repeating the experiment for 45 min (entry 6) when none of
the conjugated compound 45 was obtained and the yields of the
trans- and cis-naphthopyrans 39 and 42 were increased to 55 and
23%, respectively. In this case, the phenanthrene yield was also
increased to 15%.
When the reaction temperature was reduced to 45◦C and the
time to 20 min (entry 7), the pyrans were not observed whereas

936
R. G. F. Giles et al.
R2
MeO
O
OH
R1
R
R1 ϭ R2 ϭ OMe
R1 ϭ H, R2 ϭ OMe
R1 ϭ OMe, R2 ϭ H
R1 ϭ R2 ϭ H
7 R ϭ OMe
8 R ϭ H
3
4
5
6
R2
R2
OH
OH
1
R1
R1
9
R1 ϭ OMe, R2 ϭ Et
12 R1 ϭ OMe, R2 ϭ Et
13 R1 ϭ R2 ϭ Et
10 R1 ϭ R2 ϭ Et
11 R1 ϭ Et, R2 ϭ OMe
14 R1 ϭ OMe, R2 ϭ H
R2
R2
CO2Me
R1
OR1
15 R1 ϭ COMe, R2 ϭ Et
16 R1 ϭ H, R2 ϭ Et
21 R1 ϭ OH, R2 ϭ CO2Me
22 R1 ϭ OMe, R2 ϭ CO2Me
23 R1 ϭ OMe, R2 ϭ CHO
24 R1 ϭ OTf, R2 ϭ CO2Me
25 R1 ϭ Et, R2 ϭ CO2Me
26 R1 ϭ Et, R2 ϭ CHO
17 R1 ϭ CH2CHϭCH2, R2 ϭ Et
18 R1 ϭ COMe, R2 ϭ H
19 R1 ϭ R2 ϭ H
20 R1 ϭ CH2CHϭCH2, R2 ϭ H
O
O
O
R
27 R ϭ OMe
28 R ϭ Et
29
Ϫ
O
OϪ
O
29
H
H
Me MgI
30
Scheme 2.
26
31
the mixture of conjugated alcohols 45 and the phenanthrene 46
were isolated in 60 and 5% yields, respectively, together with
starting material (∼10%) as estimated from the 1H NMR spec-
trum because it could not be separated from the conjugated
isomer 45.
The conjugation of the allyl group in 10 to give the mixture
45 occurs through a base-induced proton migration (prototropic
rearrangement) and a more extensive variant provides a plausible
mechanism for the formation of phenanthrene 46 (Scheme 3).
Two proton migrations, one in compound 10 and the other in
intermediate 47, would provide the hexatriene 48 that would
undergo an electrocyclization to form 49 from which two
molecules of hydrogen could be lost (or, alternatively, one hydro-
gen molecule could be lost earlier, from, e.g. 48, and then follow
a related route) to give 46. This tentative mechanism would
explain why such phenanthrenes were not observed for either
of the ortho-methoxy allylnaphthalenes 1 or 9, neither of which
possessed an ethyl group at C1.
When the alcohol 11 was cyclized at 60◦C for 40 min under
nitrogen, the sole product, isolated in 70% yield, was the trans-
naphthopyran 40 (entry 8). When the time was extended to 2 h
(entry 9), the trans- and cis-products 40 and 43 were isolated
in respective yields of 58 and 16%. When the same reaction
was performed without the exclusion of air (entry 10), these
trans- and cis-products were isolated in yields of 23 and 17%,
respectively, together with an inseparable mixture of C4 epimeric
alcohols 50 and 51 in a combined yield of 31% and in a respec-
tive ratio of 3:1. Such oxidation has been observed previously
in the cyclization of naphthalene 1 to naphthopyran 2 in air,
and also on treatment of the naphthopyran 2 with t-butoxide

Naphthopyrans and their C4 Alcohols
937
Table 1. Reactions of alcohols 9–14 with potassium t-butoxide in dry dimethylformamide
Entry
Substrate
ConditionsA
(T [◦C], t [min],
atmosphere)
Naphthopyran
product(s)
(total yield %)
Naphthopyrans
(individual
yields %)
Naphthopyran
ratio
Other products
%
1B
9
9
9
60, 30, N2
60, 45, N2
60, 60, N2
60, 120, N2
60, 30, N2
60, 45, N2
45, 20, N2
60, 40, N2
60, 120, N2
60, 120, air
60, 120, N2
60, 60, N2
38 (69)
38 (69)
38 (100):41 (0)
38 (83):41 (17)C
38 (73):41 (27)C
38 (62):41 (38)
39 (80):42 (20)
39 (70):42 (30)
–
40 (100):43 (0)
40 (78):43 (22)
40 (58):43 (42)
–
–
–
–
–
2C
38 + 41 (68)
38 + 41 (68)
38 + 41 (69)
39 + 42 (54)
39 + 42 (78)
39 + 42 (0)
40 (70)
40 + 43 (74)
40 + 43 (40)
57 (69)
38 (56) + 41 (12)
38 (50) + 41 (18)
38 (43) + 41 (26)
39 (43) + 42 (11)
39 (55) + 42 (23)
–
3C
4B
9
5B
10
10
10
11
11
11
12
13
14
45 (37) + 46 (6)
6B
45 (0) + 46 (15)
7B
45 (60) + 46 (5)
8B
40 (70)
–
–
9B
40 (58) + 43 (16)
40 (23) + 43 (17)
–
10B
11B
12B
13B
50 (23) + 51 (8)
–
–
58 (72)
–
–
60, 7200 (120 h), air
59 (25)
AIn DMF, KOtBu (4 equiv.).
BIsolated yield of individual products.
CYields determined by 1H NMR analysis.
in dimethylformamide in air, when the alcohols 52 and 53 were
obtained in a ratio of 1:4 in a yield of 35%.[1] The isolation of the
alcohols 50 and 51 in yields comparable with those obtained in
the related aerobic reactions of naphthalene 1 and naphthopyran
2 shows that an oxygen substituent at C5 of the naphthopyran is
not required for the oxidative step.
the only 2-benzopyran-4-ol hitherto known[20,21] to have this
unusual inverted conformation for the pyran ring. In particu-
lar, there is close agreement between the chemical shifts for the
3-CH3 doublets and the H3/H4 coupling constants, viz. δ 1.18
and 2.6 Hz for compound 50 and δ 1.21 and 2.2 Hz for com-
pound 54.
1
In the H NMR spectrum of the mixture of compounds 50
We have recently shown[20–22] that, for 2-benzopyrans such
as 54, the relative intensities of the 1,8- and 4,5-peri-interactions
determine the conformation adopted by the dihydropyran half-
chair. In the 5,10-dimethoxynaphthopyran case 53, the C3
methyl prefers to adopt the equatorial orientation always hith-
erto found[23–25] for such 5,10-dioxygenated naphthopyrans,
whereas the C1 methyl is pseudoaxial to minimize 1,10-peri-
interactions and the C4 hydroxy group is pseudoequatorial,
possibly aided to a minor degree through hydrogen bonding
to the C5 oxygen. (That this hydrogen bonding is not strong
is suggested by the chemical shift of the hydroxyl proton at
δ ∼ 4). Replacement of the C5 oxygen steric requirement in 53
by that of the larger methylene group in analogue 50 is suf-
ficient to require the inversion of the half-chair conformation,
thereby allowing the C4 hydroxy group to adopt the pseudoax-
ial conformation to minimize this increased 4,5-peri-interaction
at the expense of both the C3 methyl becoming axial and the
C1 methyl pseudoequatorial, despite of the latter increasing the
1,10-peri-interaction.This is the first example of a dihydronaph-
thopyran adopting the inverted conformation of the half-chair.
Furthermore, it is the first example, to our knowledge, of a
dihydropyran in which the C1 methyl with a neighbouring peri-
methoxy group adopts a pseudoequatorial orientation. In the
three previous cases in which this inversion was observed in iso-
lated products,[20–22] the peri-substituent was a hydrogen atom.
We have also proposed[20,26] a transition state involving such a
conformational inversion leading to the synthesis of a natural
product derivative.
and 51, both the major and minor diastereoisomers showed
signals attributable to the same structural entities for two C4
epimeric alcohols, including, about the pyran rings, two methyl
substituents and three one-proton heterocyclic protons. There
were two anomalies, however, the first in that both products
showed the small H3/H4 coupling constants of 2.6 and 1.3 Hz for
the major and minor diastereoisomers respectively, both being
consistent with small dihedral angles between these protons. In
all other related 5,10-dimethoxynaphthopyrans formed in this
manner,[1,4,5] the pseudoaxial alcohol (e.g. 52) showed a small
coupling constant of ∼2 Hz,[19] whereas in the corresponding
pseudoequatorial alcohol (e.g. its epimer 53), the related cou-
pling constant was ∼7–8 Hz,[19] reflecting the large dihedral
angle between the axial proton H3 and the pseudoaxial pro-
ton H4. Closer inspection revealed a second anomaly in that
the chemical shift, δ 1.18, of the 3-CH3 protons of the major
diastereoisomer 50 was at significantly higher field than that
normally shown,[4,5] e.g. at δ 1.43 for the C4 pseudoequatorial
alcohol 53 (Table 2).
Individual assignments for the alcohols 50 and 51 were made
through comparison of their 1H NMR spectra with those of
related compounds (Table 2). The minor diastereoisomer was
assigned structure 51 as its resonances compared closely with
those of the known[19] 5,10-dimethoxy analogue 52 (for which
the only structural difference was the C5 substituent), particu-
larly for those signals attributable to protons further from the
respective C5 substituents (Table 2). The major diastereoisomer
was assigned structure 50 in which the half-chair conforma-
tion of the dihydropyran ring was inverted relative to that in
structure 53,[19] for which the conformations are depicted in the
respective part-structures 55 and 56, respectively. This stereo-
chemical assignment is supported through the comparison of
the 1H NMR spectra of compounds 50 and 54, the latter being
Two further observations are also noteworthy, first that the
1,3-trans, 3,4-trans (trans/trans) alcohol 50 predominated over
the trans/cis epimer 51 in this oxidation process, as found[1,4,5]
for all the pairs of C4 epimeric alcohols produced under the
aerobic conditions of this reaction, in spite of the alternative
conformation found in the product 50. Second, a comparison

938
R. G. F. Giles et al.
MeO
Table 2. Chemical shifts (δ), coupling constants (J Hz), and instrument
operating frequencies (MHz) for naphthopyrans 50–53 and benzopyran
54 determined in CDCl3
O
R2
R2
50
51
52
53
54
R1
OR1
32 R1 ϭ OCH2CHϭCH2, R2 ϭ H
33 R1 ϭ OH, R2 ϭ CH2CHϭCH2
34 R1 ϭ OTf, R2 ϭ CH2CHϭCH2
35 R1 ϭ Et, R2 ϭ CH2CHϭCH2
36 R1 ϭ H, R2 ϭ CO2Me
37 R1 ϭ Me, R2 ϭ CO2Me
MHz
200
1.18
1.68
3.87
4.34
4.68
5.22
2.6
200
1.46
1.63
3.89
4.19
4.60
5.35
1.3
100
1.44
1.61
3.90
4.14
4.78
5.35
2
100
1.43
300
1.21
1.53
–
4.32
4.63
4.85
2.2
3-CH3
1-CH3
10-OCH3
H3
H4
H1
1.70
3.90
3.9–4.3
4.81
5.26
7
R2
R2
O
O
J H3/H4
R1
R1
R1 ϭ OMe, R2 ϭ Et
R1 ϭ R2 ϭ Et
38
39
40
2
41
42
43
44
the same conditions for 1 h (entry 12) gave the naphthopyran 58
in a yield of 72%.
R1 ϭ Et, R2 ϭ OMe
R1 ϭ R2 ϭ OMe
By contrast, the less crowded analogue 14 did not react under
the standard conditions with t-butoxide under nitrogen. In the
presence of air, however, reaction did occur slowly (over 120 h)
and 9-methoxyanthracene[27] 59 was isolated in 25% yield, for
whichthe 1HNMRspectrumshowedonlyaromaticandmethoxy
protons in a ratio of 3:1. A possible mechanism (Scheme 4)
involving an oxidation process would be the slow conversion of
thealcohol 14intothecorrespondingaldehyde 61underthereac-
tion conditions, presumably via the conjugated alkoxide anion
60. Subsequent proton abstraction from the allyl substituent of
61 would lead to the cyclization of anion 62 and dehydration of
the derived alcohol 63 to give the observed product 59. Simpler
mechanisms not involving an oxidative step would not explain
the necessity for air.
OH
OH
45
46
OH
OH
H
H
Ϫ O
H
H
Ϫ O
47
10
Conclusions
The generality of the cyclizations of 2-allyl-3-(1ꢀ-hydroxyethyl)-
1,4-dimethoxynaphthalenes with tert-butoxide in dimethylfor-
mamide to afford naphtho[2,3-c]pyrans has been extended
through replacement of either or both of the methoxy groups
with ethyl substituents. To make valid comparisons, the condi-
tions used in the present study were identical to those originally
reported for the cyclization of 1 to 2.[1] Each of the naphthalenes
9–11 fully substituted in one ring cyclized, as did the correspond-
ing hydroxymethyl derivatives 12 and 13, whereas the trisubsti-
tuted analogue 14 failed to provide a naphthopyran. For the naph-
thalenes 9–11, the product naphthopyrans were 1,3-disubstituted
and the first-formed kinetic products were 1,3-trans while more
prolonged treatment yielded increasing quantities of the corre-
sponding thermodynamically favoured 1,3-cis-isomers, as was
established for the conversion of the 1,4-dimethoxy compounds
such as 1 into the 1,3-dimethylnaphthopyrans 2.[1] The yields of
the naphthopyrans obtained through cyclizations for the ethy-
lated compounds 9–13 were of the order of 70% compared with
generallyhigheryields(87%tovirtuallyquantitative)forthevar-
ious 1,4-dimethoxy substrates investigated.[1,4,5] The yields for
the cyclizations of the 1-hydroxyethyl derivatives 9–11 and their
hydroxymethyl analogues 12 and 13 were similar, suggesting
that the extramethyl in the former group did not play a significant
role in these reactions. The isolation of the two naphthopyran-
4-ols 50 and 51 under aerobic conditions confirmed that a C5
oxygen was not required for their formation, a process that
has previously been shown to occur through oxidation of the
1,3-trans-dimethylnaphthopyrans.[1,4] The conformation of the
OH
Ϫ 2H2
OH
46
49
48
Scheme 3.
of the ratio of products obtained on reaction of naphthalene 11
under anaerobic and aerobic conditions while other conditions
remained constant (Table 1, entries 9 and 10) shows that the yield
of the cis-dimethylnaphthopyran 43 remains approximately con-
stant, while that of the trans epimer 40 is reduced by 35% in the
aerobic reaction and the combined yield of the C4 epimeric alco-
hols 50 and 51 rises by 31%. This observation strongly suggests
that these alcohols are formed from the trans-pyran 40 once this
is formed in solution, a view also supported by the fact that the
only alcohols observed have the trans-1,3-dimethyl stereochem-
istry.Thisisconsistentwiththepreviouslyreported[1] conversion
of pyran 2 into epimeric alcohols 52 and 53, while 44, the C1
epimer of 2, was found not to react.[1]
Cyclization of alcohol 12 with t-butoxide under nitrogen for
2 h afforded the naphthopyran 57 as the sole product in a yield
of 69% (entry 11). Likewise the alcohol 13 when treated under

Naphthopyrans and their C4 Alcohols
939
MeO
MeO
aЈ
eЈ
OH
O
1
4
O
O
10
5
a
5
MeO
e
MeO
aЈ
OH
aЈ
OH
MeO
MeO
65
R
64
50
51 R ϭ Et
52 R ϭ OMe
Fig. 1.
MeO
aЈ
Experimental
eЈ
1
O
10
5
1
O
8
5
General
e
4
a
4
All 1H and 13C NMR spectra were measured on either a Varian
60, 80, XL 100, Gemini 200 MHz or a Bruker Advance DPX
300 MHz spectrometer for solutions in deuterochloroform as
solvent using CHCl3 as internal standard. Coupling constants
J are quoted in Hz. Unless otherwise stated, IR spectra were
measured for Nujol mulls on a Perkin-Elmer FTIR Paragon 2000
spectrometer. Mass spectra were recorded on a VG Micromass
16F mass spectrometer. Solvents of recrystallization are given in
parentheses after melting points. Preparative layer chromatogra-
phy (PLC) was performed on glass plates coated with Merck
Kieselgel 60F254, whereas column chromatography refers to
dry-packed columns using the same gel (70–230 mesh). Hex-
ane refers to that fraction of bp 60–75◦C and ether to diethyl
ether. The phrase ‘residue obtained on workup’ refers to the
residue obtained when the organic layer was separated, dried
(MgSO4), and the solvent evaporated under reduced pressure.
In NMR spectra, assignments with the same superscript may be
interchanged.
eЈ
OH
MeO
aЈ
OH
MeO
Cl
53
54
aЈ
HO
a
O
eЈ
Me
H3
aЈ
e
Me
eЈ
HO
Me
eЈ
H4
aЈ
H3
H1
e
H
1 eЈ
O
H
aЈ
a
Me
55
56
O
R
MeO
57 R ϭ OMe
58 R ϭ Et
59
O
H
H
Methyl 4-Ethyl-1-hydroxy-3-naphthoate 16
OϪ
The acetate 15[15] (2.37 g, 8.71 mmol) was dissolved in a sodium
hydroxide solution (0.75%) in methanol (150 mL) and sub-
sequently stirred at 25◦C for 30 min and then acidified with
hydrochloric acid (0.5 M). After removal of the methanol under
reduced pressure, the thick mobile residue was diluted with
water (150 mL) and exhaustively extracted with ethyl acetate.
The residue obtained on workup was chromatographed (30%
ethyl acetate/hexane) to give naphthoate 16 (2.00 g, 100%) as
white crystals, mp 143–144.5◦C (isopropyl alcohol) (Found:
C 73.1, H 6.2. C14H14O3 requires C 73.1, H 6.2%). νmax/cm−1
3320, 1725. δH (100 MHz) 1.35 (3H, t, J 7.8, CH2CH3), 3.31
(2H, q, J 7.8, CH2CH3), 3.95 (3H, s, OCH3), 6.01 (1H, s,
1-OH), 7.23 (1H, s, H2), 7.60 (2H, m, H6, H7), 8.18 (1H, m, H5)
and 8.28 (1H, m, H8). δC 15.9 (CH2CH3), 22.5 (CH2CH3), 52.3
(OCH3), 108.5 (C2), 122.5 (C6)a, 125.4 (C7)a, 126.67 (C3)b,
126.73 (C5)c, 126.9 (C4)b, 127.1 (C8)c, 133.1 (C4a)d, 135.8
(C8a)d, 149.8 (C1) and 169.2 (C=O). m/z 230 (M+, 93%), 215
(100), 171 (34), 170 (26), 141 (25), 115 (36).
14
MeO
MeO
60
61
OH
O
59
Ϫ
MeO
MeO
62
63
Scheme 4.
dihydropyran ring in pyranol 50 is inverted relative to that in its
C4 epimer 51.
It appears that steric compression is essential for cyclizations
to occur in good yields, for the limited number of substrates
investigated, but that the involvement of as yet undefined elec-
tronic factors may be necessary to achieve the excellent yields
observed for the formation of 2[1] and related examples.[4–10]
Further support for this conjecture is the recently reported[28]
cyclization of the dimethoxy-substituted benzenoid system 64,
a regioisomeric analogue of 3, to give solely the trans-1,3-
dimethyl-2-benzopyran 65 (Fig. 1) in 96% yield at a somewhat
increased temperature (80◦C).
Methyl 1-Allyloxy-4-ethyl-3-naphthoate 17
Naphthoate 16 (2.0 g, 8.7 mmol) dissolved in acetone (150 mL)
was treated with anhydrous potassium carbonate (3.60 g,
26.0 mmol) and allyl bromide (2.24 mL, 3.13 g, 25.9 mmol) and
the resulting mixture was stirred vigorously and heated under
reflux for 14 h. The cooled solution was filtered and the ace-
tone was removed under reduced pressure. The residue was
dissolved in ether (200 mL) and washed with water, after which
the residue obtained on workup was chromatographed (5% ethyl
acetate/hexane)toyieldthe naphthoate 17 (1.83 g, 78%)aswhite
plates, mp 59–60◦C (hexane) (Found: C 75.7, H 6.8. C17H18O3
requires C 75.6, H 6.7%). νmax/cm−1 1723. δH (100 MHz) 1.37
The Stille coupling reactions for the conversions of 24 into
25 and 34 into 35 occurred remarkably smoothly in spite of
significant steric congestion.

940
R. G. F. Giles et al.
(3H, t, J 7.2, CH2CH3), 3.32 (2H, q, J 7.2, CH2CH3), 3.97 (3H,
s, OCH3), 4.74 (2H, dm, J 5.2, CH2CH=CH2), 5.35 (1H, dm,
J 10.6, cis CH=CH2), 5.54 (1H, dm, J 17.2, trans CH=CH2),
6.40 (1H, m, CH2CH=CH2), 7.15 (1H, s, H2), 7.60 (2H, m, H6
and H7), 8.18 (1H, m, H5), 8.38 (1H, m, H8). δC 15.9 (CH2CH3),
22.5 (CH2CH3), 52.2 (OCH3), 69.1 (OCH2), 105.1 (C2), 117.6
(CH=CH2), 122.7 (C6)a, 125.2 (C7)a, 126.7 (C5)a, 127.0 (C3)b,
127.1(C8)a, 127.8 (C4)b, 132.9(C4a)c, 133.2(CH=CH2), 135.7
(C8a)c, 152.5 (C1) and 169.2 (C=O). m/z 270 (M+, 86%), 229
(69), 197 (100), 169 (68), 141 (46).
added to the cooled mixture to destroy the excess of reagent.
The residue obtained on workup was chromatographed (30%
ethyl acetate/hexane) to yield the naphthyl alcohol 12 (1.27 g,
86%) as white crystals, mp 85–86.5◦C (hexane) (Found: C 79.6,
H 8.0. C17H20O2 requires C 79.7, H 7.9%). νmax/cm−1 3360. δH
(100 MHz) 1.33 (3H, t, J 7.8, CH2CH3), 2.05 (1H, s, 1-OH), 3.23
(2H, q, J 7.8, CH2CH3), 3.80 (2H, dm, J 5.4, ArCH2), 3.90 (3H,
s, OCH3), 4.85 (2H, s, ArCH2OH), 4.90 (1H, dq, J 18.0 and 2.1,
trans CH=CH2), 5.09 (1H, dq, J 10.2 and 2.1, cis CH=CH2),
6.10 (1H, m, CH=CH2), 7.50 (2H, m, H6 and H7) and 8.15
(2H, m, H5 and H8). δC 16.3 (CH2CH3), 21.7 (CH2CH3),
30.7 (CH2CH=CH2), 59.4 (OCH3), 62.4 (ArCH2OH), 115.5
(CH=CH2), 122.8 (C6)a, 124.8 (C7)a, 125.9 (C5)a, 126.0 (C8)a,
127.3 (C2)b, 128.2 (C3)b, 132.4 (C4)b, 134.4 (C4a)c, 136.8
(C8a)c, 139.1 (CH=CH2) and 152.8 (C1). m/z 256 (M+, 42%),
235 (100), 234 (87), 223 (48).
Methyl 2-Allyl-4-ethyl-1-hydroxy-3-naphthoate 21
Allyloxy ester 17 (786 mg, 2.91 mmol) was pyrolyzed at 180–
190◦C as a neat oil under nitrogen in an oil bath for 1 h.The dark-
ened residue was chromatographed (15% ethyl acetate/hexane)
to yield the naphthol 21 (673 mg, 86%) as an unstable oil (dark-
enedonstanding;both1HNMRspectraandTLCofthisnaphthol
showed changes after standing at 25◦C for 24 h) (Found: C 75.5,
H 6.8. C17H18O3 requires C 75.6, H 6.7%). νmax/cm−1 3490,
1732. δH (100 MHz) 1.31 (3H, t, J 7.4, CH2CH3), 2.95 (2H,
q, J 7.4, CH2CH3), 3.46 (2H, dm, J 6.2, ArCH2), 3.95 (3H, s,
OCH3), 5.24 (1H, dq, J 19.0 and 2.1, trans CH=CH2), 5.28
(1H, dq, J 11.2 and 2.1, cis CH=CH2), 5.62 (1H, s, 1-OH), 6.06
(1H, m, CH=CH2), 7.54 (2H, m, H6 and H7), 8.01 (1H, m, H5)
and 8.25 (1H, m, H8). δC 15.9 (CH2CH3), 23.8 (CH2CH3), 33.3
(CH2CH=CH2), 52.1 (OCH3), 117.1 (CH=CH2), 122.3 (C6)a,
124.4 (C7)a, 125.8 (C2)b, 126.0 (C4)b, 126.5 (C5)a, 126.6 (C8)a,
129.8 (C3)b, 131.3 (C4a)c, 132.2 (C8a)c, 135.7 (CH=CH2),
148.8 (C1) and 170.8 (C=O). m/z 270 (M+, 100%), 255 (89),
239 (15), 223 (26).
2-Allyl-4-ethyl-1-methoxynaphthalene-3-carbaldehyde 23
and Either 9-Ethyl-4-methoxy-1,3-dihydronaphtho[2,3-
c]furan-1(3H)-3-one 27 or its Regioisomer 4-Ethyl-
9-methoxy-1,3-dihydronaphtho[2,3-c]furan-1(3H)-3-one
To a solution of alcohol 12 (500 mg, 1.95 mmol) in ben-
zene (200 mL) was added activated manganese dioxide (4.0 g,
4.6 mmol) and the resultant mixture was heated under reflux
with vigorous stirring for 5 h. The cooled mixture was filtered
and the residue obtained on workup was chromatographed (10%
ethyl acetate/hexane) to afford the aldehyde 23 (310 mg, 63%)
as orange crystals, mp 127–128◦C (hexane) (Found: C 80.5, H
7.3. C17H18O2 requires C 80.3, H 7.1%). νmax/cm−1 1694. δH
(200 MHz) 1.37 (3H, t, J 7.2, CH2CH3), 3.34 (2H, q, J 7.2,
CH2CH3), 3.91 (5H, sharp m, OCH3 and CH2CH=CH2), 4.90
(1H, dq, J 17.2 and 2.2, trans CH=CH2), 5.09 (1H, dq, J 10.2
and 2.2, cis CH=CH2), 6.10 (1H, m, CH=CH2), 7.60 (2H, m,
H6 and H7), 8.19 (2H, m, H5 and H8) and 10.63 (1H, s, CHO).
δC 16.4 (CH2CH3), 21.3 (CH2CH3), 29.7 (CH2CH=CH2), 62.5
(OCH3), 116.0 (CH=CH2), 123.1 (C6)a, 125.4 (C7)a, 126.7
(C5)a, 127.0 (C2)b, 128.1 (C8)a, 130.3 (C4)b, 131.8 (C3)b, 132.9
(C4a)c, 137.7 (CH=CH2), 140.8 (C8a)c, 152.9 (C1) and 195.0
(C=O). m/z 254 (M+, 20%), 253 (100), 223 (80), 225 (43), 213
(80). Further elution afforded the γ-lactone 27 (80 mg, 17%)
as light red crystals, mp 148–149◦C (hexane) (Found: C 74.5,
H 5.9; M+ 242.0938. C15H14O3 requires C 74.4, H 5.9%; M
242.0943). νmax/cm−1 1746. δH (200 MHz) 1.30 (3H, t, J 7.4,
CH2CH3), 2.96 (2H, q, J 7.4, CH2CH3), 4.33 (3H, s, OCH3),
5.38 (2H, s, ArCH2O), 7.57 (1H, tm, J 8.4, 6H), 7.70 (1H, tm, J
8.4, H7), 8.04 (1H, dm, J 8.4, H5), 8.43 (1H, dm, J 8.4, H8). δC
14.4 (CH2CH3), 21.6 (CH2CH3), 63.8 (OCH3), 68.5 (ArCH2O),
110.6 (C3a)a, 123.5 (C6)b, 124.9 (C7)b, 125.9 (C5)b, 128.2
(C9a)a, 128.6 (C9)a, 129.4 (C8)b, 135.9 (C4a)c, 138.4 (C8a)c,
156.3 (C4), 169.2 (C=O).
Methyl 2-Allyl-4-ethyl-1-methoxy-3-naphthoate 22
To freshly prepared naphthol 21 (563 mg, 2.09 mmol) dissolved
in acetone (100 mL) was added potassium carbonate (863 mg,
6.25 mmol) and dimethyl sulfate (0.61 mL, 813 mg, 6.26 mmol)
and the mixture was heated under reflux with vigorous stirring
under nitrogen for 2 h. The cooled mixture was filtered, the ace-
tone removed under reduced pressure, and the residue taken up in
ether. The organic extract was washed successively with ammo-
nia (25%), water, hydrochloric acid (1 M), and finally water. The
residue obtained on workup was chromatographed (5% ethyl
acetate/hexane) to yield the naphthoate 22 as a light yellow oil
(516 mg, 87%) (Found: C 76.1, H 7.1. C18H20O3 requires C
76.1, H 7.1%). νmax/cm−1 1726. δH (100 MHz) 1.32 (3H, t, J
7.8, CH2CH3), 2.98 (2H, q, J 7.8, CH2CH3), 3.60 (2H, dm, J 6.2,
ArCH2), 3.92 (6H, s, 2 × OCH3), 5.04 (1H, dq, J 16.8 and 2.0,
trans CH=CH2), 5.05 (1H, dq, J 11.4 and 2.0, cis CH=CH2),
5.96 (1H, m, CH=CH2), 7.54 (2H, m, H6 and H7) and 8.10
(2H, m, H5 and H8). δC 15.8 (CH2CH3), 23.9 (CH2CH3), 32.0
(ArCH2), 51.9 (ArOCH3), 62.5 (CO2CH3), 115.7 (CH=CH2),
122.9 (C6)a, 124.6 (C2)b, 124.9 (C7)a, 126.3 (C5)a, 126.6 (C8)a,
128.8 (C4)b, 131.7 (C4a)c, 132.7 (C3)b, 133.7 (C8a)c, 136.7
(CH=CH2), 152.7 (C1), 170.4 (C=O). m/z 284 (M+, 100%),
269 (36), 237 (36).
2-Allyl-4-ethyl-3-(1ꢀ-hydroxyethyl)-
1-methoxynaphthalene 9
Into a freshly prepared solution of methyl magnesium iodide
(from magnesium (85 mg, 3.54 mmol) and methyl iodide
(500 mg, 3.54 mmol)) in ether (25 mL) was dripped aldehyde 23
(300 mg, 1.18 mmol)inether(25 mL)over15 minundernitrogen
withstirringat25◦C.Afteranadditionalstirringperiodof1 h, the
reaction mixture was treated with sufficient saturated aqueous
ammonium chloride to destroy the excess of reagent and water
(100 mL)wasaddedandtheaqueoussolutionthenextractedwith
2-Allyl-4-ethyl-3-hydroxymethyl-1-methoxynaphthalene 12
A solution of the ester 22 (1.63 g, 5.74 mmol) in ether (100 mL)
was added dropwise to a stirred slurry of lithium aluminium
hydride (436 mg, 11.5 mmol) in ether (50 mL) over 15 min at
25◦C. Stirring was continued for a further 5 h and then the mix-
ture was heated under reflux for an additional 1.5 h, after which
sufficient saturated ammonium chloride solution was slowly

Naphthopyrans and their C4 Alcohols
941
ether. The residue obtained on workup was chromatographed
(30% ethyl acetate/hexane) to afford the naphthyl alcohol 9 as
a thick oil (270 mg, 85%) (Found: C 80.0, H 8.1. C18H22O2
requires C 80.0, H 8.2%). νmax/cm−1 3420. δH (200 MHz) 1.35
(3H, t, J 7.4, CH2CH3), 1.64 (3H, d, J 7.0, [CH(OH)CH3]),
1.94 (1H, s, [CH(OH)CH3]), 3.37 (2H, q, J 7.4, CH2CH3), 3.80
(2H, m, ArCH2CH=CH2), 3.89 (3H, s, OCH3), 4.87 (1H, dq,
J 17.2 and 2.2, trans CH=CH2), 5.07 (1H, dq, J 10.2 and 2.2,
cis CH=CH2), 5.53 (1H, q, J 7.0, [CH(OH)CH3]), 6.09 (1H,
m, CH=CH2), 7.49 (2H, m, H6 and H7), 8.09 (2H, m, H5 and
H8). δC 16.4 (CH2CH3), 21.7 [CH(OH)CH3], 23.5 (CH2CH3),
31.0 (CH2CH=CH2), 62.2 (OCH3), 68.0 [CH(OH)CH3], 115.2
(CH=CH2), 122.8 (C6)a, 124.8 (C7)a, 125.5 (C5)a, 125.8 (C8)a,
126.4 (C2)b, 127.6 (C3)b, 132.9 (C4)b, 135.2 (C4a)c, 138.8
(CH=CH2), 139.1 (C8a)c, 153.1 (C1). m/z 270 (M+, 29%), 252
(100), 225 (63), 223 (36), 221 (52), 211 (60).
(C8a)c, 171.4 (C=O). m/z 282 (M+, 24%), 251 (100), 223 (60),
182 (48).
2-Allyl-1,4-diethyl-3-hydroxymethylnaphthalene 13
To a slurry of lithium aluminium hydride (900 mg, 23.7 mmol)
in ether (100 mL) was added dropwise with stirring a solution of
ester 25 (4.18 g, 14.82 mmol) in ether (100 mL) over 20 min after
which the mixture was stirred and heated under reflux for 18 h.
Workup as described earlier afforded the naphthyl alcohol 13
(2.63 g, 70%) as white cubes, mp 121–122◦C (hexane) (Found:
C 84.7, H 8.5; M+ 254.1675. C18H22O requires C 85.0, H 8.7%;
M 254.1671). νmax/cm−1 3335. δH 1.32 (6H, m, CH2CH3), 1.56
(1H, s, CH2OH), 3.07 (2H, q, J 7.2, CH2CH3), 3.26 (2H, q, J 7.0,
CH2CH3), 3.78 (2H, m, CH2CH=CH2), 4.82 (1H, dq, J 17.2
and 2.2, trans CH=CH2), 4.88 (2H, s, CH2OH), 5.80 (1H, dq,
J 10.2 and 2.2, cis CH=CH2), 6.20 (1H, m, CH=CH2), 7.51
(2H, m, H6 and H7), 8.10 (2H, m, H5 and H8). δC 15.3 and 16.3
(CH2CH3), 22.0and22.1(CH2CH3), 33.5(CH2CH=CH2), 59.9
(ArCH2OH), 115.7 (CH=CH2), 124.8 (C6)a, 125.1 (C7)a, 125.2
(C8)a, 125.9 (C5)a, 131.4 (C1)b, 132.3 (C2)b, 133.1 (C3)b, 134.3
(C4)b, 137.2 (C4a)c, 138.3 (CH=CH2), 138.5 (C8a)c.
Methyl 2-Allyl-4-ethyl-1-trifluoromethanesufonyloxy-
3-naphthoate 24
Allyloxy ester 17 (2.8 g, 10.4 mmol) was pyrolyzed at 180–
200◦C under nitrogen with stirring for 1 h, after which the cooled
darkened material was dissolved in pyridine (16 mL) and stirred
under nitrogen at this temperature. Trifluoromenthanesulfonic
anhydride (3.5 g, 12.4 mmol) was then dripped into the solution
and stirring maintained for a further 15 min and then allowed
to reach 25◦C at which temperature stirring was continued for
12 h. The residue obtained on workup as described earlier was
chromatographed (10% ethyl acetate/hexane) and this afforded
the naphthyl triflate 24 as a pale yellow oil (3.33 g, 80%)
(Found: C 53.8, H 4.1. C18H17F3O5S requires C 53.7, H 4.3%).
νmax/cm−1 1727. δH (200 MHz) 1.35 (3H, t, J 7.2, CH2CH3),
3.02 (2H, q, J 7.2, CH2CH3), 3.70 (2H, dm, J 6.2, ArCH2), 3.72
(3H, s, OCH3), 5.09 (1H, dq, J 16.2 and 2.2, trans CH=CH2),
5.10 (1H, dq, J 11.0 and 2.2, cis CH=CH2), 5.90 (1H, m,
CH=CH2) 7.64 (2H, m, H6 and H7), 8.12 (2H, m, H5 and H8).
δC 15.5 (CH2CH3), 24.1 (CH2CH3), 32.6 (CH2CH=CH2), 52.2
(OCH3), 117.0 (CH=CH2), 122.3 (q, J 318.0, CF3), 124.8 (C6)a,
127.2 (C2)b, 127.3 (C3)b, 127.5 (C7)a, 127.7 (C4)b, 128.3 (C5)a,
131.6 (C4a)c, 132.5 (C8a)c, 134.2 (C8)a, 138.8 (CH=CH2),
141.4 (C1), 169.0 (C=O). m/z 403 (M+ + 1, 27%), 402 (M+,
23), 269 (100), 238 (70), 210 (60).
2-Allyl-1,4-diethylnaphthalene-3-carbaldehyde 26 and
4,9-Diethyl-1,3-dihydronaphtho[2,3-c]furan-3-one 28
To a solution of alcohol 13 (420 mg, 1.65 mmol) in ben-
zene (120 mL) was added activated manganese dioxide (3.0 g,
3.5 mmol) and the mixture was stirred and heated under reflux
for 4 h and worked up as described above to yield aldehyde 26 as
athickorangeoil(270 mg, 65%)(Found:C85.5, H7.7. C18H20O
requires C 85.7, H 8.0%). νmax/cm−1 1695. δH (200 MHz) 1.34
(6H, m, CH2CH3), 3.10 (2H, q, J 7.8, CH2CH3), 3.28 (2H, t,
J 7.8, CH2CH3), 3.78 (2H, m, CH2CH=CH2), 4.86 (1H, dq, J
17.2 and 2.1, trans CH=CH2), 5.10 (1H, dq, J 10.2 and 2.1, cis
CH=CH2), 6.10 (1H, m, CH=CH2), 7.58 (2H, m, H6 and H7),
8.12 (1H, dm, J 8.2, H5), 8.22 (1H, dm, J 8.2, H8), 10.63 (1H, s,
CHO). δC 15.1 and 16.3 (CH2CH3), 21.4 and 21.7 (CH2CH3),
33.1 (CH2CH=CH2), 116.2 (CH=CH2), 124.9 (C6)a, 125.5
(C7)a, 125.8 (C5)a, 127.7 (C8)a, 131.4 (C1)b, 131.9 (C2)b,
132.8(C3)b, 133.9(C4)b, 137.0(CH=CH2), 137.6(C4a)c, 141.3
(C8a)c, and 196.0 (C=O). m/z 252 (M+, 90%), 251 (100), 223
(64), 211 (36). Further elution afforded the γ-lactone 28 (73 mg,
18%) as olive-green needles, mp 150–151◦C (hexane) (Found:
C 79.9, H 6.5; [M]+ 240.1130. C16H16O2 requires C 80.0, H
6.7%; M 240.1150). νmax/cm−1 1745. δH (200 MHz) 1.33 (6H,
m, CH2CH3), 3.02 (2H, q, J 7.2, CH2CH3), 3.69 (2H, q, J 7.6,
CH2CH3), 5.38 (2H, s,ArCH2O), 7.66 (2H, m, H6 and H7), 8.14
(1H, dm, J 8.0, H5), 8.32 (1H, dm, J 8.1, H8). δC 14.5 and 15.8
(CH2CH3), 19.4 and 22.0 (CH2CH3), 67.9 (ArCH2O), 119.0
(C3a)a, 124.3 (C6)b, 126.2 (C7)b, 126.3 (C5)b, 128.4 (C8)b,
131.6 (C9a)a, 132.5 (C4)a, 134.5 (C9)a, 137.8 (C4a)c, 143.7
(C8a)c, 171.5 (C=O).
Methyl 2-Allyl-1,4-diethyl-3-naphthoate 25
To a solution of triflate 24 (2.13 g, 5.3 mmol) in dry dimethylfor-
mamide (80 mL) containing bis(triphenylphosphine)dichloro-
palladium(ii) (60 mg, 0.09 mmol), lithium chloride (1.0 g,
23.8 mmol), and 2,6-di-t-butyl-4-methylphenol (50 mg,
0.23 mmo1) was added tetraethyltin (5.13 g, 21.9 mmol) and the
resulting solution was stirred and heated at 85◦C under nitro-
gen for 96 h and then worked up as described before to afford
the diethylnaphthalene 25 as a light yellow oil (1.43 g, 96%)
(Found: C 80.7, H 7.7. C19H22O2 requires C 80.8, H 7.9%).
νmax/cm−1 1731. δH (200 MHz) 1.32 (6H, m, CH2CH3), 3.05
(4H, m, CH2CH3), 3.53 (2H, dm, J 5.8, CH2CH=CH2), 3.95
(3H, s, OCH3), 5.00 (1H, dq, J 17.0 and 2.1, trans CH=CH2),
5.06 (1H, dq, J 10.0 and 2.1, cis CH=CH2), 6.00 (1H, m,
CH=CH2), 7.53 (2H, m, H6 and H7) and 8.08 (2H, m, H5 and
H8). δC 15.0 and 15.6 (CH2CH3), 21.4 and 24.1 (CH2CH3), 35.3
(CH2CH=CH2), 51.8 (OCH3), 115.5 (CH=CH2), 124.7 (C6)a,
124.9 (C7)a, 125.4 (C5)a, 126.3 (C8)a, 126.5 (C1)b, 129.4 (C2)b,
130.4(C4)b, 132.5(C3)b, 135.0(C4a)c, 136.6(CH=CH2), 137.3
4,9-Diethyl-1-vinyl-1,3-dihydronaphtho[2,3-c]furan 29 and
2-Allyl-1,4-diethyl-3-(1ꢀ-hydroxyethyl)naphthalene 10
Into a freshly prepared solution of methyl magnesium iodide
(from Mg (43 mg, 1.77 mmol) and methyl iodide (254 mg,
1.79 mmol)) in ether (30 mL) was added aldehyde 26 (150 mg,
0.59 mmol) as described before and the residue obtained on
workup was chromatographed (10% ethyl acetate/hexane) to
afford the naphthofuran 29 as a thick oil (30 mg, 20%) (Found:
M+ 252.1519. C18H20OrequiresM252.1514). νmax/cm−1 1245.
δH (200 MHz) 1.28 (6H, m, CH2CH3), 2.99 (4H, m, CH2CH3),

942
R. G. F. Giles et al.
5.21 (1H, d, J 12.6, pseudoaxial H3), 5.27 (1H, dm, J 10.1,
cis CH=CH2), 5.33 (1H, J 12.6, pseudoequatorial H3), 5.47
(1H, dm, J 17.0, trans CH=CH2), 5.82 (1H, dm, J 7.8, H1),
6.04 (1H, m, CH=CH2), 7.50 (2H, m, H6 and H7) and 8.06
(2H, m, H5 and H8). δC 14.6 and 14.9 (CH2CH3), 22.2 and
23.2 (CH2CH3), 71.6 (C3), 85.2 (C1), 116.9 (CH=CH2), 124.7
(C6)a, 124.5 (C7)a, 125.1 (C8)a, 125.3 (C5)a, 130.8 (C4)b, 132.1
(C9)b, 132.2 (C3a)b, 132.3 (C9a)b, 135.5 (C4a)c, 136.2 (C9a)c,
137.6 (CH=CH2). Further elution (30% ethyl acetate/hexane)
gave the naphthyl alcohol 10 as a thick viscous oil (100 mg,
63%) (Found: C 84.9, H 8.7. C19H24O requires C 85.0, H 9.0%).
νmax/cm−1 3320. δH 1.32 (200 MHz) (6H, m, CH2CH3), 1.67
(3H, d, J 6.8, CH(OH)CH3), 1.84 (1H, s, [CH(OH)CH3]), 3.06
(2H, q, J 7.8, CH2CH3), 3.38 (2H, ill-defined q, CH2CH3), 3.78
(2H, m, CH2CH=CH2), 4.80 (1H, dq, J 17.2 and 2.1, trans
CH=CH2), 5.09 (1H, dq, J 10.2 and 2.1, cis CH=CH2), 5.59
(1H, q, J 6.8, CH(OH)CH3), 6.18 (1H, m, CH=CH2), 7.49 (2H,
m, H6 and H7), 8.14 (2H, m, H5 and H8). δC 15.3 and 16.3
(CH2CH3), 21.9 and 22.0 (CH2CH3), 23.4 [CH(OH)CH3], 33.8
(CH2CH=CH2), 68.3 [CH(OH)CH3], 115.6 (CH=CH2), 124.7
(C6)a, 125.0 (C7)a, 125.1 (C5)a, 125.4 (C8)a, 131.7 (C1)b, 131.8
(C2)b, 131.9 (C3)b, 136.7 (C4)b, 137.8 (C4a)c, 138.4 (C8a)c,
138.6 (CH=CH2). m/z 268 (M+, 19%), 250 (100), 223 (46),
221 (33), 209 (32).
water (100 mL), followed by 25% aqueous ammonia (100 mL),
water, and hydrochloric acid (0.1 M, 100 mL), and finally
water. The residue obtained on workup was chromatographed
(10% ethyl acetate/hexane) to give naphthalene 35 as a yellow
oil (540 mg, 75%) (Found: C 80.4, H 7.6. C18H20O2 requires
C 80.6, H 7.5%). νmax/cm−1 1703. δH (200 MHz) 1.28 (3H,
t, J 7.4, CH2CH3), 2.61 (3H, s, COCH3), 3.07 (2H, q, J 7.4,
CH2CH3), 3.53 (2H, dt, J 5.4 and 1.8, ArCH2CH=CH2), 3.89
(3H, s, OCH3), 4.90 (1H, dq, J 17.2 and 1.8, trans CH=CH2),
5.07 (1H, dq, J 10.2 and 1.8, cis CH=CH2), 5.98 (1H, m,
CH=CH2), 7.54 (2H, m, H6 and H7), 8.10 (2H, m, H5 and
H8). δC 15.2 (CH2CH3), 21.4 (COCH3), 33.1 (CH2CH=CH2)a,
33.6 (CH2CH3)a, 63.6 (OCH3), 116.2 (CH=CH2), 122.7 (C6)b,
124.6 (C7)b, 125.6 (C5)b, 126.9 (C2)c, 127.1 (C8)b, 129.9 (C3)c,
133.4 (C4a)d, 133.6 (C8a)d, 135.6(C4)c, 136.8 (CH=CH2),
151.1 (C1), 206.8 (C=O). m/z 268 (M+, 70%), 253 (100), 239
(30), 237 (18), 227 (47), 225 (50).
2-Allyl-1-ethyl-3-(1ꢀ-hydroxyethyl)-
4-methoxynaphthalene 11
Using the method described for the reduction of ester 22, ketone
35 (580 mg, 2.16 mmol) was reduced with lithium aluminium
hydride to afford the alcohol 11 as an oil (560 mg, 96%) (Found:
C 79.9, H 8.4. C18H22O2 requires C 80.0, H 8.2%). νmax/cm−1
3412, 1634. δH (200 MHz)1.28(3H, t, J7.6, CH2CH3), 1.66(3H,
d, J 6.8, CH(OH)CH3), 3.04 (2H, dq, J 7.6 and 2.2, CH2CH3),
3.63 (2H, m, CH2CH=CH2), 4.06 (3H, s, OCH3), 4.22 (1H,
d, J 7.8, CH(OH)CH3), 4.84 (1H, dq, J 17.2 and 2.2, trans
CH=CH2), 5.10 (1H, dq, J 10.2 and 2.2, cis CH=CH2), 5.27
(1H, q, J 6.8, CH(OH)CH3), 6.10 (1H, m, CH=CH2), 7.50 (2H,
m, H6 and H7), 8.05 (2H, m, H5 and H8). δC 15.3 (CH2CH3),
21.8 [CH(OH)CH3], 25.1 (CH2CH3), 33.1 (CH2CH=CH3),
63.5 (OCH3), 67.5 [CH(OH)CH3], 116.1 (CH=CH2), 122.5
(C6)a, 124.6 (C7)a, 125.1 (C5)a, 126.0 (C8)a, 127.2 (C2)b,
132.0 (C4a)b, 132.6 (C8a)b, 133.2 (C4)b, 135.4 (C3)b, 136.9
(CH=CH2), 152.8 (C1). m/z 270 (M+, 22%), 252 (100), 239
(10), 223 (46), 221 (60), 211 (36).
3-Acetyl-2-allyl-4-methoxy-1-trifluoromethane-
sulfonyloxynaphthalene 34
2-Acetyl-4-allyloxy-1-methoxynaphthalene 32[17] (588 mg,
2.29 mmol) was pyrolyzed at 175◦C in an oil bath under nitrogen
for 7 h to afford the intermediate naphthol 33.The cooled residue
was dissolved in dry pyridine (2.5 mL) and further cooled to
0◦C at which time trifluoromethanesulfonic anhydride (676 mg,
2.40 mmol) was added dropwise under nitrogen and the resulting
solution was stirred for an additional 5 min. This was allowed to
warm to 25◦C and then stirred for a further 18 h after which it
was quenched with water (100 mL) and the aqueous mixture was
extracted with ether. The ether extracts were washed consecu-
tively with water, hydrochloric acid (1 M, thrice), water, and
brine. The residue obtained on workup was chromatographed
(10% ethyl acetate/hexane) to afford the naphthyl triflate 34
as a light yellow oil (703 mg, 83%) (Found: C 52.8, H 4.1.
C17H15F3O5S requires C 52.6, H 3.9%). νmax/cm−1 1703. δH
(300 MHz) 2.62 (3H, s, COCH3), 3.67 (2H, dt, J 6.1 and 1.6,
ArCH2), 3.92 (3H, s, OCH3), 4.99 (1H, dq, J 17.1 and 1.6,
trans CH=CH2), 5.11 (1H, dq, J 10.2 and 1.6, cis CH=CH2),
5.85 (1H, ddt, J 17.1, 10.2 and 6.1, CH=CH2), 7.66 (2H, m,
H6 and H7), 8.12 (2H, m, H5 and H8). δC 31.1 (COCH3)a,
33.0 (ArCH2)a, 64.0 (OCH3), 117.8 (CH=CH2), 118.7 (q, J
320.3, CF3), 122.1 (C6)b, 122.6 (C7)b, 127.5 (C5)b, 127.8 (C2)c,
128.0 (C3)c, 128.5 (C4a)d, 129.0 (C8)b, 132.7 (C8a)d, 134.3
(CH=CH2), 139.0 (C4), 153.1 (C1), 203.7 (C=O). m/z 388 (M+,
7%), 256 (50), 241 (100), 226 (22).
Methyl 1-Allyloxy-3-naphthoate 20
Ester 19[18] (1.03 g, 5.1 mmol) in dry acetone (90 mL) was
treated with potassium carbonate (2.11 g, 15 mmol) and allyl
bromide (1.29 mL, 1.80 g, 15 mmol) and the resultant mixture
was rapidly stirred and heated under reflux for 4 h. The cooled
solution was filtered and worked up as described for 17 to yield
after chromatography the naphthoate 20 (1.23 g, 100%) as an
oil (Found: C 74.5, H 5.9. C15H14O3 requires C 74.4, H 5.8%).
νmax/cm−1 (film) 1715 cm. δH (100 MHz) 3.96 (3H, s, OCH3),
4.76 (2H, m, ArOCH2), 5.46 (2H, m, CH=CH2), 6.20 (1H, m,
CH=CH2), 7.39 (1H, d, J 2, H2), 7.58 (2H, m, H6 and H7), 7.89
(1H, m, H5), 8.21 (1H, d, J 2, H4), 8.33 (1H, m, H8). m/z 242
(M+, 87%), 202 (17), 201 (100), 143 (53).
3-Acetyl-2-allyl-1-ethyl-4-methoxynaphthalene 35
Methyl 2-Allyl-1-hydroxy-3-naphthoate 36
To a solution of triflate 34 (1.04 g, 2.68 mmol) in dry dimethyl-
formamide(20 mL)containingbis(triphenylphosphine)dichloro-
palladium(ii) (20 mg, 0.03 mmol), lithium chloride (0.34 g,
8.02 mmol), and 2,6-di-t-butyl-4-methylphenol (30 mg,
13.6 mmol) was added tetraethyltin (2.60 g, 11.07 mmol) and the
resulting solution was stirred under nitrogen at 85◦C for 96 h.
The cooled reaction mixture was dissolved in ether (150 mL) and
washed with aqueous (10%) ammonium fluoride (100 mL), then
Allyloxy ester 20 (697 mg, 2.88 mmol) was heated neat under
nitrogen for 1.5 h in an oil bath at 180◦C. The darkened oil was
chromatographed (3% ethyl acetate/hexane) to afford naphthol
36 (645 mg, 94%) as white needles, mp 62.5–63.5◦C (hexane)
(Found: C 74.4, H 6.0. C15H14O3 requires C 74.4, H 5.9%).
νmax/cm−1 3460, 1689. δH (100 MHz) 1.30 (1H, s, 1-OH), 3.89
(2H, m, ArCH2), 3.91 (3H, s, OCH3), 5.17 (2H, m, CH=CH2),
6.10 (1H, m, CH=CH2), 7.54 (2H, m, H6 and H7), 7.82 (1H, m,

Naphthopyrans and their C4 Alcohols
943
H5), 8.03 (1H, s, H4), 8.18 (1H, m, H8). m/z 242 (M+, 100%),
227 (17), 183 (26), 182 (42), 181 (48).
elution with the same solvent yielded naphthopyran 38 (23 mg,
43%) as colourless plates, mp 106–107◦C (hexane) (Found: M+
270.1615. C18H22O2 requires M 270.1620). νmax/cm−1 1260.
δH (200 MHz) 1.28 (3H, t, J 7.6, CH2CH3), 1.39 (3H, d, J 5.8,
3-CH3), 1.61 (3H, d, J 6.6, 1-CH3), 2.64 (1H, dd, J 17.0 and
11.0, pseudoaxial H4), 3.00 (2H, dq, J 7.6 and 4.0, CH2CH3),
3.17 (1H, dd, J 17.0 and 3.6, pseudoequatorial H4), 3.89 (3H, s,
OCH3), 4.26 (1H, m, H3), 5.37 (1H, q, J 6.6, H1), 7.46 (2H, m,
H7 and H8) and 8.05 (2H, m, H6 and H9). δC 15.4 (CH2CH3),
20.5 (3-CH3), 21.8 (1-CH3), 22.5 (CH2CH3), 30.9 (C4), 60.8
(OCH3), 62.3 (C3)a, 70.1 (C1)a, 122.3 (C7)b, 122.5 (C4a)c,
124.4 (C8)b, 125.1 (C9)b, 125.6 (C6)b, 127.0 (C10a)c, 130.7
(C10)c, 131.5 (C5a)c, 135.0 (C9a)c, 151.6 (C5).
Repeating the reaction on alcohol 9 (58 mg, 0.21 mmol) and
using potassium t-butoxide (96 mg, 0.86 mmol) under the same
conditions but for 30 min afforded naphthopyran 38 (40 mg,
69%) as the sole product. The ratios of naphthopyrans 41 and 38
estimated from NMR integrations after 45 min were 17:83 and
after 60 min were 27:73.
Methyl 2-Allyl-1-methoxy-3-naphthoate 37
Naphthol 36 (694 mg, 2.87 mmol) dissolved in acetone (60 mL)
was treated with potassium carbonate (1.19 g, 8.6 mmol) and
dimethyl sulfate (0.78 mL, 1.04 g, 8.6 mmol) and the mixture
was rapidly stirred and heated under reflux under nitrogen
for 1.5 h. The cooled mixture was filtered and the acetone
was removed under reduced pressure to produce an oil, which
was taken up in ether (150 mL) and washed successively with
ammonia (25%), water, hydrochloric acid (0.5 M), and water.
The residue obtained on workup was chromatographed (15%
ethyl acetate/hexane) to yield the oily naphthoate 37 (691 mg,
94%) (Found: C 75.1, H 6.3. C16H16O3 requires C 75.0, H
6.3%). νmax/cm−1 1729. δH (100 MHz) 3.91 (6H, s, 2 × OCH3),
3.92 (2H, m, ArCH2), 4.63 (2H, m, CH=CH2), 6.06 (1H, m,
CH=CH2), 7.57 (2H, m, H6 and H7), 7.88 (1H, m, H5), 8.10
(1H, m, H8), 8.20 (1H, s, H4). m/z 256 (M+, 100%), 241 (24),
209 (58), 182 (31), 181 (43).
cis-5,10-Diethyl-3,4-dihydro-1,3-dimethyl-1H-naphtho
[2,3-c]pyran 42, trans-5,10-Diethyl-3,4-dihydro-1,3-
dimethyl-1H-naphtho[2,3-c]pyran 39, (Z)- and (E)-1,4-
Diethyl-3-(1ꢀ-hydroxyethyl)-2-(prop-1ꢀ-enyl)naphthalene
45, and 9-Ethyl-10-(1ꢀ-hydroxethyl)-4-
2-Allyl-3-hydroxymethyl-1-methoxynaphthalene 14
To a stirred suspension of lithium aluminium hydride (87 mg,
2.28 mmol) in ether (20 mL) was added dropwise a solution
of ester 37 (157 mg, 0.61 mmol) under nitrogen over 10 min at
25◦C. After an additional 10 min stirring, sufficient saturated
aqueous ammonium chloride was added to destroy the excess of
reagent. The residue obtained on workup was chromatographed
(30% ethyl acetate/hexane) to give the title compound 14 as
a thick oil (130 mg, 93%) (Found: C 79.0, H 6.9. C15H16O2
requires C 78.9, H 7.1%). νmax/cm−1 3330. δH (100 MHz) 1.97
(1H, br s, CH2OH), 3.68 (2H, m, ArCH2CH=CH2), 3.92 (3H, s,
OCH3), 4.80 (2H, s, ArCH2OH), 4.96 (2H, m, CH=CH2), 6.08
(1H, m, CH=CH2), 7.50 (2H, m, H6 and H7), 7.77 (1H, s, H4),
7.81 (1H, m, H5), 8.07 (1H, m, H8). m/z 228 (M+, 100%), 210
(16), 195 (75), 179 (26), 165 (55).
methylphenanthrene 46
To a solution of alcohol 10 (80 mg, 0.30 mmol) in dimethyl-
formamide (12 mL) under nitrogen in an oil bath at 60◦C was
added at once potassium t-butoxide (135 mg, 1.20 mmol) and
the resulting solution, which turned from colourless to orange
brown, was stirred for 45 min and then worked up as described
before to afford naphthopyran 42 as a colourless oil (18 mg,
23%) (Found: M+ 268.1830. C19H24O requires M 268.1827).
νmax/cm−1 1264. δH (200 MHz) 1.26 (3H, t, J 7.6, CH2CH3),
1.32 (3H, t, d, J 7.2, CH2CH3), 1.42 (3H, d, J 6.2, 3-CH3), 1.49
(3H, d, J 6.6, 1-CH3), 2.73 (1H, dd, J 15.8 and 10.6, pseudoaxial
H4), 2.95 (1H, dd, J 15.8 and 2.4, pseudoequatorial H4), 3.07
(4H, m, CH2CH3), 3.70 (1H, ddq, J 10.6, 6.2, and 2.4, H3), 5.48
(1H, q, J 6.6, H1), 7.47 (2H, m, H7 and H8), 8.06 (2H, m, H6
and H9). δC 11.1 (CH2CH3), 14.8 (CH2CH3)a, 15.5 (3-CH3)a,
20.8 (1-CH3)a, 21.2 and 25.9 (CH2CH3), 33.1 (C4), 72.1 (C3)b,
73.1 (C1)b, 124.5 (C7)c, 124.7 (C8)c, 125.2 (C6)c, 125.4 (C9)c,
129.2 (C5)d, 131.0 (C4a)d, 131.1 (C10a)d, 133.5 (C10)d, 134.2
(C5a)d, 135.1 (C9a)d. Further elution afforded the naphthopy-
ran 39 as a colourless oil (44 mg, 55%) (Found: M+ 268.1832.
C19H24O requires M 268.1827). νmax/cm−1 1265. δH (200 MHz)
1.29 (6H, m, CH2CH3), 1.41 (3H, d, J 6.0, 3-CH3), 1.64 (3H, d,
J 6.6, 1-CH3), 2.70 (1H, dd, J 16.8 and 11.0, pseudoaxial H4),
3.06 (5H, m, CH2CH3 and pseudoequatorial H4), 4.35 (1H, m,
H3), 5.42 (1H, q, J 6.6, H1), 7.47 (2H, m, H7 and H8) and
8.07 (2H, m, H6 and H9). δC 10.5 (CH2CH3), 14.4 (CH2CH3)a,
15.4 (1-CH3)a, 20.6 (3-CH3), 21.5 and 21.9 (CH2CH3), 32.2
(C4), 67.3 (C3)b, 70.8 (C1)b, 124.4 (C7)c, 124.6 (C8)c, 125.2
(C6)c, 125.3 (C9)c, 126.7 (C5)d, 130.7 (C4a)d, 131.2 (C10a)d,
132.8 (C10)d, 133.7 (C5a)d, 136.1 (C9a)d. The final compound
to elute was phenanthrene 46 (12 mg, 15%) as light yellow crys-
tals, mp 146–147◦C (hexane) (Found: M+ 264.1509. C19H20O
requires M 264.1514). νmax/cm−1 3320. δH (200 MHz) 1.37
(3H, t, J 7.2, CH2CH3), 1.86 (3H, d, J 7.0, CH(OH)CH3), 2.58
(3H, s, 4-CH3), 3.24 (2H, m, CH2CH3), 5.95 (1H, q, J 7.0,
CH(OH)CH3), 7.42 (1H, dd, J 8.4 and 1.6, H3), 7.61 (2H, m, H6
and H7), 8.15 (1H, m, H2), and 8.64 (3H, m, H5, H8, and H1).
δC 15.5 (CH2CH3), 22.08 (4-CH3)a, 22.13 (10-CHCH3)a, 23.2
Base-Induced Cyclization Reactions
cis-10-Ethyl-3,4-dihydro-5-methoxy-1,3-dimethyl-
1H-naphtho[2,3-c]pyran 41 and
trans-10-Ethyl-3,4-dihydro-5-methoxy-1,3-dimethyl-
1H-naphtho[2,3-c]pyran 38
Potassium t-butoxide (87 mg, 0.78 mmol) was added in one
portion to alcohol 9 (53 mg, 0.196 mmol) in dimethylformamide
(18 mL) at 60◦C under nitrogen and the resulting solution was
stirred vigorously for 2 h. The cooled mixture was poured
into water (100 mL) and the organic material exhaustively
extracted with ether. The residue obtained on workup was chro-
matographed (10% ethyl acetate/hexane) to afford naphthopyran
41 as a thick oil (14 mg, 26%) (Found: C 79.9, H 8.0. C18H22O2
requires C 80.0, H 8.2%). νmax/cm−1 1258. δH (200 MHz) 1.30
(3H, t, J 7.5, CH2CH3), 1.41 (3H, d, J 6.2, 3-CH3), 1.53 (3H,
d, J 6.2, 1-CH3), 2.60 (1H, dd, J 15.6 and 10.6, pseudoaxial
H4), 3.02 (2H, q, J 7.5, CH2CH3), 3.16 (1H, dd, J 15.6 and
1.6, pseudoequatorial H4), 3.65 (1H, ddq, J 10.6, 6.2 and 1.6,
H3), 3.92 (3H, s, OCH3), 5.41 (1H, q, J 6.2, H1), 7.48 (2H,
m, H7 and H8), 8.02 (1H, m, H9), 8.14 (1H, m, H6). δC 15.6
(CH2CH3), 20.7 (3-CH3), 22.4 (1-CH3), 25.8 (CH2CH3), 32.1
(C4), 61.6 (OCH3), 69.4 (C3)a, 71.5 (C1)a, 122.4 (C7)b, 124.3
(C8)b, 124.5 (C4a)c, 125.2 (C9)b, 125.6 (C6)b, 126.9 (C10a)c,
131.6 (C10)c, 131.9 (C5a)c, 135.6 (C9a)c, 151.0 (C5). m/z 270
(M+, 55%), 269 (100), 267 (29), 255 (70), 239 (19). Further

944
R. G. F. Giles et al.
(CH2CH3), 68.3 (10-CHCH3), 122.9 (C1)b, 123.0 (C2)b, 125.0
(C3)b, 126.2 (C5)b, 126.4 (C6)b, 126.6 (C7)b, 127.4 (C8)b, 128.4
(C4)c, 129.8 (C4a)c, 130.4 (C4b)c, 130.8 (C8a)c, 134.5 (C9)c,
135.5 (C10)c, 135.7 (C10a)c.
cis-5-Ethyl-3,4-dihydro-10-methoxy-1,3-dimethyl-
1H-naphtho[2,3-c]pyran 43, trans-5-Ethyl-3,4-dihydro-
10-methoxy-1H-1,3-dimethylnaphtho[2,3-c]pyran 40,
rac-(1R,3R,4S)-5-Ethyl-4-hydroxy-3,4-dihydro-10-
methoxy-1,3-dimethyl-1H-naphtho[2,3-c]pyran 50, and
rac-(1R,3R,4R)-5-Ethyl-4-hydroxy-3,4-dihydro-10-
methoxy-1,3-dimethyl-1H-naphtho[2,3-c]pyran 51
Repeating the reaction on the alcohol 10 (68 mg, 0.22 mmol)
and stopping the reaction after 30 min afforded the following
products in order of elution: (i) naphthopyran 42 (7.5 mg; 11%);
(ii) naphthopyran 39 (29 mg; 43%); (iii) a (1:1) mixture of the
(E)/(Z) conjugated naphthyl alcohols 45 (25 mg; 37%); and (iv)
phenanthrene 46 (4 mg; 6%). Spectroscopic data for alcohol 45:
thick oil (Found: M+ 268.1820. C19H24O requires M 268.1827).
νmax/cm−1 3366. δH (300 MHz) 1.17 (3H, t, J 7.6, CH2CH3),
1.36 (3H, t, J 7.4, CH2CH3), 1.47 and 1.51 (3H, each dd, J
6.6 and 1.4, CH=CHCH3), 1.57 and 1.59 (3H, each d, J 7.0,
CH(OH)CH3), 3.04 (2H, q, J 7.6, CH2CH3), 3.36 (2H, q, J 7.4,
CH2CH3), 5.53 and 5.58 (1H, each q, J 7.0, CH(OH)CH3), 5.96
and 6.03 (1H, each dq, J ∼11.0 and 6.6, CH=CHCH3), 6.73 and
6.77 (1H, each an ill-defined dm, J ∼11, CH=CHCH3), 7.49
(2H, m, H6 and H7), 8.11 (2H, m, H5 and H8). δC 14.59, 14.65,
15.00, and 15.06 (CH2CH3), 16.11 and 16.31 [CH(OH)CH3],
21.66 and 21.85 (CH=CHCH3), 22.6, 22.73, 23.52, and 23.64
(CH2CH3), 69.04 and 69.40 [CH(OH)CH3], 124.95 (C6)a,
125.01 (C7)a, 125.31 (C5)a, 125.36 (C8)a, 127.5 (C4)b, 129.1
(C3)b, 130.2 (C2)b, 130.3 (C1)b, 131.3 (CH=CHCH3)c, 136.1
(C4a)d, 136.4 (C8a)d, 138.0 (CH=CHCH3)c.
Potassium t-butoxide (116 mg, 1.04 mmol) was added in one
portion to alcohol 11 (70 mg, 0.26 mmol) in dimethylformamide
(6 mL) in an oil bath at 60◦C and the resulting mixture was
stirred for 2 h in the presence of air. It was then worked up as
described earlier to afford after chromatography naphthopyran
43 (12 mg, 17%) followed by naphthopyran 40 (16 mg, 23%),
both having spectroscopic properties identical to those reported
above. Further elution yielded an inseparable mixture of the 4-
hydroxynaphthopyrans 50 and 51 in a ratio of 3:1 as a thick oil
(25 mg, 34%) (Found: C 75.4, H 7.8; M+ 286.1566. C18H22O3
requires C 75.5, H 7.7%; M 286.1569). νmax/cm−1 3450. δH
(major diastereoisomer) (200 MHz) 1.18 (3H, d, J 6.6, 3-CH3),
1.36 (3H, t, J 7.4, CH2CH3), 1.58 (1H, s, 4-OH), 1.68 (3H, d, J
6.4, 1-CH3), 3.24 (2H, q, J 7.4, CH2CH3), 3.87 (3H, s, OCH3),
4.34 (1H, dq, J 2.6 and 6.6, H3), 4.68 (1H, br s, H4), 5.22 (1H,
q, J 6.4, H1), 7.51 (2H, m, H7 and H8), 8.10 (2H, m, H6 and
H9). δH (minor diastereoisomer) 1.46 (3H, d, J 6.6, 3-CH3), 1.28
(3H, t, J 6.2, CH2CH3), 1.58 (1H, s, 4-OH), 1.63 (3H, d, J 6.4,
1-CH3), 3.20 (2H, q, J 6.2, CH2CH3), 3.89 (3H, s, OCH3), 4.19
(1H, dq, J 1.3 and 6.6, H3), 4.60 (1H, br s, H4), 5.35 (1H, q, J
6.4, H1), 7.51 (2H, m, H7 and H8), 8.10 (2H, m, H6 and H9).
cis-5-Ethyl-3,4-dihydro-10-methoxy-1,3-dimethyl-
1H-naphtho[2,3-c]pyran 43 and
trans-5-Ethyl-3,4-dihydro-10-methoxy-1H-1,3-
dimethylnaphtho[2,3-c]pyran 40
10-Ethyl-3,4-dihydro-5-methoxy-3-methyl-1H-
naphtho[2,3-c]pyran 57
To the alcohol 11 (80 mg, 0.30 mmol) dissolved in degassed
dimethylformamide (10 mL) as described before was added
potassium t-butoxide (134 mg, 1.20 mmol) at 60◦C and stirring
was continued for 120 min after which time the reaction mixture
was worked up as described before to yield first naphthopyran
43 (13 mg, 16%) as colourless cubes, mp 108–110◦C (hexane)
(Found: C 79.8, H 8.1; M+ 270.1622. C18H22O2 requires C 80.0,
H 8.2%; M 270.1620). νmax/cm−1 1260. δH (200 MHz) 1.24 (3H,
t, J 7.8, CH2CH3), 1.43 (3H, d, J 6.0, 3-CH3), 1.66 (3H, d, J 6.2,
1-CH3), 2.72 (1H, dd, J 15.8 and 10.6, pseudoaxial H4), 2.90
(1H, dd, J 15.8 and 2.8, pseudoequatorial H4), 3.04 (2H, dq, J
7.8 and 2.8, CH2CH3), 3.74 (1H, ddq, J 10.6, 6.0, and 2.8, H3),
3.88 (3H, s, OCH3), 5.29 (1H, q, J 6.2, H1), 7.47 (2H, m, H7 and
H8), 8.10 (2H, m, H6 and H9). δC 14.5 (CH2CH3), 21.0 (3-CH3),
22.1 (1-CH3), 22.8 (CH2CH3), 35.2 (C4), 61.1 (OCH3), 69.9
(C1)a, 71.6 (C3)a, 122.5 (C7)b, 124.0 (C8)b, 124.9 (C6)b, 125.8
(C9)b, 127.0 (C4a)c, 128.8 (C5)c, 131.4 (C9a)c, 131.7 (C5a)c,
133.0 (C10a)c, 150.7 (C10). Further elution with the same elu-
ent afforded naphthopyran 40 (46 mg, 58%) as colourless plates,
mp 113–114◦C (hexane) (Found: C 80.1, H 8.0; M+ 270.1623.
C18H22O2 requires C 80.0, H 8.2%; M 270.1620). νmax/cm−1
1258. δH (200 MHz) 1.24 (3H, t, J 7.8, CH2CH3), 1.41 (3H, d,
J 6.2, 3-CH3), 1.65 (3H, d, J 6.4, 1-CH3), 2.65 (1H, dd, J 16.8
and 10.8, pseudoaxial H4), 2.95 (1H, dd, J 16.8 and 3.6, pseudo-
equatorial H4), 3.03 (2H, dq, J 7.4 and 1.4, CH2CH3), 3.90 (3H,
s, OCH3), 4.20 (1H, m, H4), 5.36 (1H, q, J 6.4, H1), 7.49 (2H,
m, H7 and H8), 8.05 (2H, m, H6 and H9). δC 14.3 (CH2CH3),
20.78 (3-CH3)a, 20.80 (1-CH3)a, 22.3 (CH2CH3), 34.0 (C4),
61.4 (OCH3), 62.9 (C1)b, 69.1 (C3)b, 122.5 (C7)c, 124.1 (C8)c,
124.9 (C6)c, 125.7 (C9)c, 126.4 (C4a)d, 128.5 (C5a)d, 129.4
(C9a)d, 132.0 (C10a)d, 133.5 (C5)d, 149.7 (C10). Repeating the
reaction on a separate sample and stopping the reaction after
40 min afforded naphthopyran 40 as the sole product (70%).
Alcohol 12 (224 mg, 0.82 mmol) was dissolved in dimethylfor-
mamide (10 mL) that had been flushed with nitrogen for 10 min
after which potassium t-butoxide (369 mg, 3.29 mmol) was
added in one portion and the reaction mixture was then stirred
and heated at 60◦C under nitrogen for 2 h. The residue obtained
on workup as described earlier was chromatographed (15% ethyl
acetate/hexane) to afford the naphthopyran 57 (155 mg, 69%),
as white cubes, mp 81–82.5◦C (aqueous methanol) (Found:
C 79.7, H 7.8. C17H20O2 requires C 79.7, H 7.9%). νmax/cm−1
1258. δH (100 MHz) 1.20 (3H, t, J 8.0, CH2CH3), 1.42 (3H,
d, J 7.0, 3-CH3), 2.70 (3H, m, CH2CH3 and pseudoaxial H4),
3.12 (1H, dd, J 17.0 and 3.5, pseudoequatorial H4), 3.85 (3H, s,
OCH3), 3.87 (1H, m, 3-H), 4.89 (1H, d, J 17.0, pseudoaxial H1),
5.18 (1H, d, J 17.0, pseudoequatorial H1), 7.50 (2H, m, H7 and
H8), 8.08 (2H, m, H6 and H9). m/z 256 (M+, 100%), 227 (24),
225 (24), 213 (17), 212 (86), 197 (67).
5,10-Diethyl-3,4-dihydro-3-methyl-1H-naphtho[2,3-
c]pyran 58
Alcohol 13 (100 mg, 0.39 mmol) was dissolved in dimethyl-
formamide (12 mL) that had been flushed with nitrogen for
10 min and stirred under nitrogen at 60◦C at which time potas-
sium t-butoxide (176 mg, 1.57 mmol) was added at once and
stirring was continued for 1 h. The solution was then worked
up as described before to yield the naphthopyran 58 (72 mg,
72%) as white cubes, mp 89–90◦C (hexane) (Found: C 85.2,
H 8.6. C18H22O requires C 85.0, H 8.7%). νmax/cm−1 1260.
δH (200 MHz) 1.27 (6H, t, J 7.8, CH2CH3), 1.47 (3H, d, J 6.2,
3-CH3), 2.94 (6H, m, CH2CH3 and H4), 3.88 (1H, m, H3), 4.98
(1H, d, J 15.0, pseudoaxial H1), 5.20 (1H, d, J 15.0, pseudo-
equatorial H1), 7.48 (2H, m, H7 and H8), 8.08 (2H, m, H6 and

Naphthopyrans and their C4 Alcohols
945
H9). δC 14.18 and 14.24 (CH2CH3), 20.1 (3-CH3), 20.7 and 21.9
(CH2CH3), 34.4 (C4), 67.6 (C3), 70.7 (C1), 123.8 (C7)a, 124.2
(C8)a, 124.87 (C9)a, 124.92 (C6)a, 128.9 (C5)b, 129.5 (C10)b,
130.3 (C4a)b, 130.8 (C10a)b, 132.4 (C5a)c, 135.4 (C9a)c. m/z
254 (M+, 100%), 225 (26), 211 (25), 210 (74).
[10] E. M. Mmutlane, I. R. Green, J. P. Michael, C. B. de Koning, Org.
Biomol. Chem. 2004, 2, 2461. doi:10.1039/B407208A
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Trans. 1 1984, 2389. doi:10.1039/P19840002389
[12] G. M. Ramos Tombo, S. Chakrabarti, C. Ganter, Helv. Chim. Acta
1983, 66, 914. doi:10.1002/HLCA.19830660325
[13] C. M. Evans, A. J. Kirby, J. Chem. Soc., Perkin Trans. 2 1984, 1259.
doi:10.1039/P29840001259
9-Methoxyanthracene 59
Alcohol 14 (93 mg, 0.41 mmol) was dissolved in dimethylfor-
mamide (10 mL) and stirred 60◦C at which time potassium
t-butoxide(184 mg, 1.64 mmol)wasaddedatonceandtheresult-
ing mixture was stirred at the same temperature for 120 h. The
cooled mixture was poured into water (100 mL) and the organic
material exhaustively extracted with ether. The residue obtained
on workup was chromatographed (5% ethyl acetate/hexane) to
yield the known anthracene 59 (21 mg, 25%) as white needles,
mp 92◦C (hexane; lit.[27] 94◦C).
[14] C. M. Evans, A. J. Kirby, J. Chem. Soc., Perkin Trans. 2 1984, 1269.
doi:10.1039/P29840001269
[15] A. M. ElAbbady, S. H. Doss, Can. J. Chem. 1965, 43, 2408.
doi:10.1139/V65-323
[16] J. K. Stille, Angew. Chem. Int. Ed. Engl. 1986, 25, 508.
doi:10.1002/ANIE.198605081
[17] R. G. F. Giles, I. R. Green, L. S. Knight, V. R. Lee Son, S. C.Yorke, J.
Chem. Soc., Perkin Trans. 1 1994, 859. doi:10.1039/P19940000859
[18] F. G. Baddar, M. F. El-Newaihy, M. S. Ayoub, J. Chem. Soc. C 1971,
3332. doi:10.1039/J39710003332
[19] T. A. Chorn, R. G. F. Giles, I. R. Green, P. R. K. Mitchell, J. Chem.
Soc., Perkin Trans. 1 1983, 1249. doi:10.1039/P19830001249
[20] R. Aggarwal, A. A. Birkbeck, C. B. de Koning, R. G. F. Giles,
I. R. Green, S.-H. Li, F. J. Oosthuizen, Tetrahedron Lett. 2003, 44,
4535. doi:10.1016/S0040-4039(03)00986-9
Acknowledgements
Financial support from the Senate of Murdoch University and the Council
of the University of the Western Cape is gratefully acknowledged.
[21] R. G. F. Giles, I. R. Green, S.-H. Li, Aust. J. Chem. 2005, 58, 565.
doi:10.1071/CH05120
[22] R. Aggarwal, A. A. Birkbeck, R. G. F. Giles, I. R. Green,Y. Gruchlik,
F. J. Oosthuizen, Aust. J. Chem. 2003, 56, 489. doi:10.1071/CH03027
[23] D. W. Cameron, S. R. Hall, C. L. Raston, A. H. White, Aust. J. Chem.
1977, 30, 2313. doi:10.1071/CH9772313
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