Synthesis of exo enol ether-cyclic ketal isomers of substituted furanmethanol structures related to marine furanocembranoids

Article abstract of DOI:10.1016/j.tetlet.2009.12.131

Oxidations of the 2-alkenylfurans 8a and 8b, using peroxy reagents, lead to the dienedione 9 and the furan epoxide 10, respectively. Treatment of the epoxide 10 with p-TSA in MeOH produces the enol ether cyclic ketal 12, which is rapidly isomerised to the furanmethanol ether 15, isolated in 80% yield. By contrast, when the propanol-substituted furan epoxide 23 was kept in CDCl₃ containing traces of HCl for 2 h, a 3:2 mixture of Z- and E-isomers of the enol ether spiro ketals 25a and 25b was produced in >92% yield; after 24 h this mixture of isomers underwent dehydration leading to the corresponding enol ether triene 26 (70%). When a solution of the dienedione 9 in H₂O-THF containing p-TSA was stirred at 25 °C for 20 h, the tertiary alcohol 27 was produced which, after a further 20 h was converted into the furan vicinal diol 29. Likewise, when the 'cembranoid' dienedione 31 was treated with p-TSA-H₂O, the hydroxymethyl-substituted furanobutenolide 33 was produced in 40% yield. It is probable that the enol ether cyclic hemiketals 28 and 32/34, which are related to 12 and 25, and also to the naturally occurring cembranoids 1 and 2 found in corals, are transient intermediates in the conversions leading to 29 and 33 from 9 and 31, respectively.

Full text of DOI:10.1016/j.tetlet.2009.12.131

Tetrahedron Letters 51 (2010) 1280–1283
Contents lists available at ScienceDirect
Tetrahedron Letters
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Synthesis of exo enol ether-cyclic ketal isomers of substituted
furanmethanol structures related to marine furanocembranoids
*
Yi Li, Gerald Pattenden , Joseph Rogers
School of Chemistry, University of Nottingham, University Park, Nottingham, NG7 2RD, UK
a r t i c l e i n f o
a b s t r a c t
Article history:
Oxidations of the 2-alkenylfurans 8a and 8b, using peroxy reagents, lead to the dienedione 9 and the
furan epoxide 10, respectively. Treatment of the epoxide 10 with p-TSA in MeOH produces the enol ether
cyclic ketal 12, which is rapidly isomerised to the furanmethanol ether 15, isolated in 80% yield. By con-
trast, when the propanol-substituted furan epoxide 23 was kept in CDCl3 containing traces of HCl for 2 h,
a 3:2 mixture of Z- and E-isomers of the enol ether spiro ketals 25a and 25b was produced in >92% yield;
after 24 h this mixture of isomers underwent dehydration leading to the corresponding enol ether triene
26 (70%). When a solution of the dienedione 9 in H2O–THF containing p-TSA was stirred at 25 °C for 20 h,
the tertiary alcohol 27 was produced which, after a further 20 h was converted into the furan vicinal diol
29. Likewise, when the ‘cembranoid’ dienedione 31 was treated with p-TSA–H2O, the hydroxymethyl-
substituted furanobutenolide 33 was produced in 40% yield. It is probable that the enol ether cyclic hemi-
ketals 28 and 32/34, which are related to 12 and 25, and also to the naturally occurring cembranoids 1
and 2 found in corals, are transient intermediates in the conversions leading to 29 and 33 from 9 and
31, respectively.
Received 10 December 2009
Accepted 23 December 2009
Available online 7 January 2010
Ó 2010 Elsevier Ltd. All rights reserved.
exo Enol ether-cyclic ketal isomers of substituted furanmetha-
nols are found in a small group of unusual secondary metabolites,
for example, 1 and 2, isolated from corals of the genus Sinularia and
Lophogorgia.1 The metabolites co-occur with substituted furan-
methanol, furanoepoxide and Z-enedione-based diterpene ‘cem-
branes’, for example, 3, 4 and 5, to which they are probably
interrelated biosynthetically.2 It has also been suggested that exo
enol ether-containing cembranoids are key intermediates in the
CO2Me
OMe
CHO
OMe
CHO
HO
HO
O
OAc
HO
O
HO
O
O
O
OAc
O
O
OAc
HO
O
O
O
O
1
2
3
CO2Me
OH
O
H
CO2Me
H
H
H
H
H
O
HO
H
OH
O
O
OAc
OH
O
O
O
H
HO
H
H
O
O
O
OAc
O
O
O
O
O
4
5
6
7
* Corresponding author.
E-mail address: GP@nottingham.ac.uk (G. Pattenden).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.12.131

Y. Li et al. / Tetrahedron Letters 51 (2010) 1280–1283
1281
biosynthesis of more complex polycyclic diterpenes, for example,
bielschowskysin 6 and rameswaralide 7,3 found in corals, involving
novel transannular cycloaddition reactions.4 To gain a closer
insight into the likely origin of exo enol ether-cyclic ketal struc-
tures akin to 1 and 2, we have investigated their synthesis from
simple model furanoepoxide and enedione precursors related to
4 and 5.
We first examined the oxidation/hydrolysis chemistry of the
simple alkenyl furans 8a and 8b, which differ according to whether
they have a Me or a CO2Me group at C-3 in their furan rings. Thus,
treatment of the C-3 methyl substituted alkenyl furan 8a with per-
oxy reagents, that is, mCPBA, dimethyldioxirane (DMDO), Dess–
Martin periodinane (DMP), resulted in specific oxidative cleavage
of the furan ring, and formation of the Z-dienedione 9 in approx.
75% yield. By contrast, oxidation of the alkenylfuranoate 8b using
DMDO at À40 °C led to the corresponding epoxide 10 (84%). The
variation in the pattern of oxidation of 8a and 8b reflects the deac-
tivating effect of the CO2Me group in the substrate 8b towards oxi-
dation of the furan ring relative to 8a.5,6
is, dH 6.99 (s, @CH), 5.16 (s, OC@CH); dC 138.9 (d, @CH), 116.9 (d,
OC@CH) ppm established unequivocally that it had the furanmeth-
anol methyl ether structure 15, and not the isomeric dihydrofuran
enol ether structure 12 we might have anticipated.7
When the
same epoxide 10 was treated with aqueous HCl at room tempera-
ture overnight, the chlorohydrin 13 was isolated exclusively (65%),
with no evidence for the presence of the isomeric enol ether struc-
ture 14 (Scheme 1). The structure of 13 followed unambiguously
by comparison of NMR spectroscopic data with those of the iso-
meric chlorohydrin 17 produced from the alkenylfuran 8b using
aqueous N-chlorosuccinimide.8
It is likely that the products 13 and 15 are produced from the
epoxide 10 via the same oxonium ion intermediate 11 and the
enol ethers 12 and 14, respectively, which are very
rapidly isomerised under the reaction conditions to the more
stable furan derivatives. Likewise, the chlorohydrin isomer 17
of 13 is derived from the alkenylfuran 8b via the oxonium ion
species 16 [cf. 11], and possibly the isomeric enol ether [cf.
14]. In each of the experiments carried out with the substrates
10 and 8b, it is evident that the isomerisation of any enol ether
intermediates, viz. 12 and 14, to the corresponding furanmetha-
nol derivatives 13 and 15, respectively, is so rapid at ambient
temperature, as to preclude their isolation and characterisation.
Hence, in a more detailed study, a solution of epoxide 10 in
CDCl3 containing 10 equiv of methanol was treated with a crys-
tal of p-TSA at room temperature and the reaction was moni-
tored by 1H NMR spectroscopy. After 5 min (30% conversion),
the 1H NMR spectrum demonstrated the formation of the E-iso-
mer of the enol ether 12, dH 5.37 (s, OC@CH), 7.87 (s, @CH),
together with the isomeric furan structure 15 in the ratio 2:5.
After a further 10 min (80% conversion) the ratio of 12 to
15 was 1:3.9 Finally, after 25 min the only product observed
by 1H NMR spectroscopy was the furanmethanol methyl ether
15.
R
CO2Me
O
O
O
O
O
8
9
10
a, R = Me
b, R = CO2Me
When a solution of the epoxide 10 in methanol was stirred in
the presence of p-TSA at room temperature for 0.5 h, work-up
and chromatography gave a single product corresponding to over-
all addition of methanol, in 80% yield. Comparison of pertinent
NMR spectroscopic data recorded for the product, that is, dH 6.60
(s, @CH), 3.94 (s, CHOMe); dC 110.3 (d, @CH), 84.2 (d, CHOMe)
ppm, with those reported for the natural products 1 and 2, that
In an effort to intercept and isolate an enol ether correspond-
ing to 12, we next studied the acid-catalysed hydrolysis of the
CO2Me
H3O+
CO2Me
CO2Me
OMe
ii
O
O
O
O
HO
HO
10
11
12
i
CO2Me
Cl
CO2Me
CO2Me
MeO
HO
Cl
O
O
O
HO
HO
14
13
15
CO2Me
CO2Me
CO2Me
HO
Cl
iii
O
O
O
Cl
8b
16
17
Scheme 1. Reagents and conditions: (i) aq HCl (2 M), rt overnight, 65%; (ii) MeOH, p-TSA (cat.), rt 0.5 h, 80%; (iii) NCS, H2O, CH2Cl2, rt 2 d, 49%.

1282
Y. Li et al. / Tetrahedron Letters 51 (2010) 1280–1283
CO2Me
CO2Me
BzO
i
I
+
OTBS
OTBS
O
BzO
O
18
19
20
CO2Me
CO2Me
CO2Me
iv
iii
ii
OH
O
OTBS
O
OTBS
O
O
O
21
22
23
CO2Me
HO
CO2Me
CO2Me
O
O
v
O
O
O
HO
HO
24
25
26
a, Z-isomer
b, E-isomer
Scheme 2. Reagents and conditions: (i) NaH, THF, 0 °C, 72%; (ii) Pd(OAc)2, dppf, K2CO3, CH3CN/H2O (10:1), rt 50%; (iii) DMDO, acetone, 0 °C, 78%; (iv) TBAF, THF, rt 71%; (v)
HCl–CDCl3, 70%.
substrate 23 which is substituted with a propanol group at C-2
HO
H3O+
OH
in the furan ring. We anticipated that this propanol group might
participate by quenching any oxonium ion species produced
from 23, that is, 24, in an intramolecular fashion, thereby leading
to an isolable enol ether. The substrate 23 was prepared by
alkylation of the anion derived from the b-keto ester 18,10 with
the propargyl iodide 19,11 followed by cyclisation of the result-
ing substituted b-keto ester 20 to the furan 21 using the condi-
tions described by Wipf et al.12 (Scheme 2). Epoxidation of the
alkenylfuran 21 using DMDO next gave the epoxide 22 which
was then deprotected using TBAF, leading to the desired propa-
nol-substituted furan epoxide 23.
When a solution of the epoxide 23 in CDCl3 (containing traces
of HCl) was left at room temperature for 0.5 h, 1H NMR spectro-
scopic analysis showed that it was converted (30%) into a 4:3
mixture of Z-[dH 5.00 (OC@CH), 6.92 (@CH)], and E-[dH 5.35
(OC@CH), 7.83 (@CH)] isomers of the exo enol ether spiroketal
structures 25a and 25b, respectively.13 After 2 h, the conversion
of 23 into 25a and 25b (ratio 3:2) was essentially complete
(>92%),14 and when the solution was left for a further 24 h, the
only product isolated, in 70% yield, was a single isomer of enol
ether triene 26, resulting from dehydration of 24/25.15 The Z-ste-
reochemistry assigned to 26 followed from a NOESY correlation
analysis.
In a separate study, a solution of the Z-dienedione 9 in H2O–THF
containing p-TSA was stirred at room temperature and the pro-
gress of the reaction was monitored by 1H NMR spectroscopy. After
ca. 20 h, work-up and chromatography gave the tertiary alcohol 27
(10%), resulting from hydration of the terminal alkene bond in 9, as
the first-formed product.16 When the reaction of 9 with p-TSA in
H2O–THF was left longer, or when the hydroxyenedione 27 was
treated again with p-TSA–H2O–THF for ca. 20 h, the only product
isolated was the furan vicinal diol structure 29.16 As with the epox-
ide 10, we believe that the enol ether 28 is a likely intermediate in
the conversion of 9 and 27 into 29, but the isomerisation of 28 into
29 is too rapid under the reaction conditions to allow its separate
isolation.
O
O
9
O
O
HO
HO
HO
27
29
28
Finally, we examined the acid-catalysed isomerisation of a Z-
dienedione contained within a macrocyclic cembranoid, that is,
31, with the expectation that this substrate would be ‘locked’ con-
formationally, thereby favouring the formation of an isolable enol
ether-cyclic hemiketal, that is, 32. Thus, oxidative cleavage of the
furan ring in the furanobutenolide 30 (rubifolide), first gave
the enedione 31 (also known as isoepilophodione B).17 When the
enedione 31 was treated with p-TSA–H2O, a single product was
isolated in 40% yield, whose spectroscopic data were consistent
with the hydroxymethyl-substituted alkenylfuran structure 3318
and not with the structure 32. Indeed, reduction of the alcohol
group in the product, using Et3SiH–TFA in CH2Cl2 at 0 °C, regener-
ated rubifolide 30 in 56% yield. We rationalise the formation of 33
from 31, taking place by acid-catalysed hydration–enolisation of
31 via the enol ether intermediates 32 and 34, followed by isomeri-
sation of 34 to the corresponding alkenylfuran 33. Once again,
therefore, our efforts to interrupt the rapid isomerisation of enol
ether-cyclic hemiketals to their furan counterparts, and to isolate
cembranoid compounds, viz. 32, similar in constitution to natural
products, that is, 1 and 2, were thwarted.
In conclusion, the enol ether cyclic ketals 12 and 25, having
structural features in common with the novel cembranoid natu-
ral products 1 and 2, have been synthesised and characterised.
Similar enol ethers have been implicated in the conversions of
the epoxide 10, the 2-alkenylfuran 8b, and the dienediones 9
and 31 into the substituted furans 13, 17, 29 and 33, respec-
tively. However, further studies, involving subtle changes to
the structures of precursors are required before a clearer insight
into the origin of cembranoid enol ether cyclic ketals and their
importance in biosynthetic pathways is to be forthcoming. These
investigations are in progress in our laboratory.

Y. Li et al. / Tetrahedron Letters 51 (2010) 1280–1283
1283
OH
O
m
CPBA
O
p
-TSA
H2O
O
O
HO
O
O
O
O
O
O
31
30
32
Et3SiH/TFA
O
OH
HO
O
O
O
O
O
34
33
(s), 150.1 (s), 113.9 (s), 109.5 (d), 75.5 (d), 73.8 (s), 51.4 (q), 29.5 (q), 27.1 (q),
13.8 (q); HRMS (ESI) 269.0517 (M+Na+, C11H15ClO4Na requires 269.0557).
9. The enol ether cyclic ketal 12 showed: dH (400 MHz, CDCl3): 7.87 (1H, s, @CH),
5.37 (1H, s, OC@CH), 3.81 (3H, s, CO2Me), 3.14 (3H, s, OMe), 2.58 (3H, s,
MeOCMe), 1.70 (3H, s, CMeMe), 1.42 (3H, s, CMeMe).
10. Heslin, J. C.; Moody, C. J. J. Chem. Soc., Perkin Trans. 1 1988, 1417–1423.
11. The iodide 19 was prepared from propargyl chloride following: (i)
deprotonation (n-BuLi) and alkylation with acetone, (ii) protection of the
resulting alcohol (Bz2O, Et3N, MgBr2), and (iii) exchange of chloride for iodide
under Finkelstein conditions (NaI, acetone).
Acknowledgements
We thank the EPSRC for a Fellowship (to Y.L.) and for a Student-
ship (to J.R.). We also thank Merck for support, and Bencan Tang
and Amael Veyron for some initial studies in this area.
References and notes
12. (a) Rahmann, L. T.; Rector, S. R.; Wipf, P. J. Org. Chem. 1998, 63, 7132; (b) Wipf,
P.; Soth, M. J. Org. Lett. 2002, 4, 1787–1790.
1. (a) Kamel, H. N.; Ferreira, D.; Garcia-Fernandez, L. F.; Slattery, M. J. Nat. Prod.
2007, 70, 1223–1227; (b) Venkateswarlu, Y.; Sridevi, K. V.; Rama Rao, M. J. Nat.
Prod. 1999, 62, 756–758; (c) Epifánio, R. de A.; Maria, L. F.; Fenical, W. J. Braz.
Chem. Soc. 2000, 11, 584–591; (d) Sánchez, M. C.; Ortega, M. J.; Zubia, E.;
Carballo, J. L. J. Nat. Prod. 2006, 69, 1749–1755; (e) Grote, D.; Dahse, H.-M.;
Seifert, K. Chem. Biodiv. 2008, 5, 2449–2456.
13. Interestingly, exo enol ether spiroketal metabolites have been isolated from
Compositae, alongside polyacetylenic compounds which are thought to be their
biosynthetic precursors; see Bohlmann, F.; Burkhardt, T.; Zdero, C. Naturally
Occurring Acetylenes, Academic Press, London and New York, 1973. Furthermore,
related heterocyclic structures have recently been synthesised and shown to
have insectanti-feedant properties; see Yin, B.-L.; Chen, L.; Xu, H.-H.; Zhang, J.-C.;
Wu, Y.-L. Chin. J. Chem. 2007, 25, 808–813, and references therein.
2. For a recent summary of furanocembranes and related natural products, see:
Roethle, P. A.; Trauner, D. Nat. Prod. Rep. 2008, 25, 298–317.
3. Bielschowskysin: (a) Marrero, J.; Rodríguez, A. D.; Baran, P.; Raptis, R. G.;
Sánchez, J. A.; Ortega-Barria, E.; Capson, T. L. Org. Lett. 2004, 6, 1661–1664;
Rameswaralide: (b) Ramesh, P.; Srinivasa Reddy, N.; Venkateswarlu, Y.;
Venkata Rami Reddy, M.; Faulkner, D. J. Tetrahedron Lett. 1998, 39, 8217–8220.
4. For contemporaneous studies directed towards rameswaralide based on a
biogenetically inspired transannular [4+3] cycloaddition approach, see:
Pattenden, G.; Winne, J. M. Tetrahedron Lett. 2009, 50, 7310–7313.
5. The oxidations of furans, leading to dienediones and 2,5-dialkoxy-2,5-
dihydrofurans have been studied extensively. So to have the oxidations of
furanmethanols, leading to pyranones, precursors to oxidopyrylium ions. See
for example: (a) Achmatowicz, O., Jr.; Bukowski, P.; Szechner, B.;
Zweierzchowska, Z.; Zamojski, A. Tetrahedron 1971, 27, 1973–1996; (b)
Burke, M. D.; Berger, E. M.; Schreiber, S. L. J. Am. Chem. Soc. 2004, 126,
14095–14104; (c) Burke, M. D.; Schreiber, S. L. Angew. Chem., Int. Ed. 2004, 43,
46–58; (d) Singh, V.; Krishna, U. M.; Vikrant; Trivedi, G. K. Tetrahedron 2008, 64,
3405–3428; (e) Harris, J. M.; O’Doherty, G. A. Tetrahedron Lett. 2000, 41, 183–
187; (f) Takeuchi, M.; Taniguchi, T.; Ogasawara, K. Synthesis 1999, 2, 341–354;
(g) Wender, P. A.; Rice, K. D.; Schnute, M. E. J. Am. Chem. Soc. 1997, 119, 7897–
7898; (h) Doncaster, J. R.; Etchells, L. L.; Kershaw, N. M.; Nakamura, R.; Ryan,
H.; Takeuchi, R.; Sakaguchi, K.; Sardarian, A.; Whitehead, R. C. Bioorg. Med.
Chem. Lett. 2006, 16, 2877–2881.
14. The Z-enol ether 25a showed: dH (400 MHz, CDCl3): 6.92 (1H, s, @CH), 5.0 (1H,
s, OC@CH), 4.21–4.03 (2H, m, OCH2), 3.81 (3H, s, OMe), 2.65–2.56 (1H, m,
OCH2CHH), 2.25–2.10 (3H, m, OCH2CHHCH2), 1.44 (3H, s, CMeMe), 1.42 (3H, s,
CMeMe); The E-enol ether 25b showed: dH (400 MHz, CDCl3): 7.83 (1H, d, J 0.4,
@CH), 5.35 (1H, d, J 0.4, OC@CH), 4.21–4.03 (2H, m, OCH2), 3.81 (3H, s, OMe),
2.65–2.56 (1H, m, OCH2CHH), 2.25–2.10 (3H, m, OCH2CHHCH2), 1.44 (3H, s,
CMeMe), 1.42 (3H, s, CMeMe); HRMS (ESI) 277.1043 (M+Na+, C13H18O5Na
requires 277.1052).
15. The Z-enol ether triene 26 showed: dH (400 MHz, CDCl3): 6.96 (1H, s, @CH),
5.31 (1H, s, OC@CH), 5.18 (1H, br s, @CHH), 4.97 (1H, br s, @CHH), 4.18 (1H,
app. dt, J 7.5 and 4.5, OCHH), 4.08 (1H, app. q, J 7.4, OCHH), 3.81 (3H, s, OMe),
2.63–2.53 (1H, m, OCH2CHH), 2.30–2.12 (3H, m, OCH2CHHCH2), 2.15 (3H, s,
@CMe); dC (100 MHz, CDCl3): 168.2 (s), 157.9 (s), 153.1 (s), 140.3 (s), 138.1 (d),
132.2 (s), 117.0 (t), 109.8 (d), 69.8 (t), 51.7 (q), 35.1 (t), 25.1 (t), 22.4 (q); HRMS
(ESI) 237.1119 (M+H+, C13H17O4 requires 237.1127).
16. The b-hydroxyketone 27 showed: m
max (film)/cmÀ1 3642, 3516, 1704, 1614; dH
(400 MHz, CDCl3): 6.03 (1H, q, J 1.5, @CH), 3.53 (1H, br s, Me2COH), 2.67 (2H, s,
CH2), 2.32 (3H, s, COMe), 2.00 (3H, d, J 1.5, @CMe), 1.27 (6H, s, Me2COH); dC (100
MHz, CDCl3): 206.6 (s), 200.2 (s), 156.7 (s), 124.6 (d), 69.8 (s), 53.3 (t), 29.4
(2 Â q), 28.0 (q), 20.3 (q); HRMS (ESI) 207.0989 (M+Na+, C10H16O3Na requires
207.0992). The furan vicinal diol 29 showed mmax (CHCl3 solution)/cmÀ1 3578,
2927, 1704, 1672; dH (300 MHz, CDCl3): 6.08 (1H, s, @CH), 4.38 (1H, br s,
CH(OH)C), 2.19 (3H, s, @CMe), 1.92 (3H, s, @CMe), 1.28 (3H, s, MeMeC), 1.26
(2H, br s, 2 Â OH), 1.19 (3H, s, MeMeC); dC (75 MHz, CDCl3): 150.7 (s), 147.0 (s),
114.5 (s), 111.3 (d), 74.7 (q), 73.1 (s), 26.0 (q), 25.0 (q), 11.4 (q), 9.8 (q); HRMS
(ESI) 207.0988 (M+Na+, C10H16O3Na requires 207.0992). For a special example
of the transition of a cyclic bis-ketal enedione to an exo enol ether-cyclic ketal,
where the enol ether is part of a vinylogous carbonate, see: Etchells, L. L.;
Sardarian, A.; Whitehead, R. C. Tetrahedron Lett. 2005, 46, 2803–2807.
6. For contemporaneous studies of the oxidative cleavage of the furanocembrane-
based natural product bipinnatin J, leading to intricarene by way of
a
transannular [5+2] (1,3-dipolar) cycloaddition reaction, see: Tang, B.; Bray, C.
D.; Pattenden, G. Tetrahedron Lett. 2006, 47, 6401–6404; Tang, B.; Bray, C. D.;
Pattenden, G. Org. Biomol. Chem. 2009, 7, 4448–4457; See also: Roethle, P. A.;
Hernandez, P. T.; Trauner, D. Org. Lett. 2006, 8, 5901–5904.
7. The furanmethanol methyl ether 15 showed: dH (400 MHz, CDCl3): 6.60 (1H, s,
@CH), 3.94 (1H, s, CH(OMe)), 3.83 (3H, s, C(O)OMe), 3.32 (3H, s, (MeO)CH), 3.28
(1H, s, MeMeC(OH)), 2.59 (3H, s, @CMe), 1.22 (3H, s, MeMeC(OH)), 1.21 (3H, s,
MeMeC(OH)); dC (100 MHz, CDCl3): 164.5 (s), 159.3 (s), 149.8 (s), 113.8 (s),
110.3 (d), 84.2 (d), 72.5 (s), 57.6 (q), 51.3 (q), 25.9 (q), 24.5 (q), 13.9 (q); HRMS
(ESI) 265.1043 (M+Na+, C12H18O5Na requires 265.1052).
8. The chlorohydrin 13 showed: dH (400 MHz, CDCl3): 6.69 (1H, s, @CH), 4.86 (1H,
s, CH(Cl)C), 3.84 (3H, s, C(O)OMe), 2.61 (3H, s, MeC@), 2.29 (1H, br s,
MeMeC(OH)),1.39 (3H, s, MeMeCH(OH)), 1.37 (3H, s, MeMeCH(OH)); dC
(100 MHz, CDCl3): 164.1 (s), 159.5 (s), 149.0 (s), 114.2 (s), 110.7 (d), 73.0 (s),
64.9 (d), 51.5 (q), 26.9 (q), 25.8 (q), 13.9 (q). The isomeric chlorohydrin 17
showed: dH (400 MHz, CDCl3): 6.63 (1H, s, @CH), 4.64 (1H, d, J 5.2, CH(OH)C),
3.81 (3H, s, CO2Me), 2.65 (1H, d, J 5.2, CH(OH)C), 2.57 (3H, s, MeC@), 1.67 (3H, s,
MeMeCH(Cl)), 1.65 (3H, s, MeMeCH(Cl)); dC (100 MHz, CDCl3): 164.3 (s), 158.9
17. Roethle, P. A.; Hernandez, P. T.; Trauner, D. Org. Lett. 2006, 8, 5901–5904.
18. The 19-hydroxyrubifolide 33 showed: mmax (CHCl3 solution)/cmÀ1 3452, 1748,
1646, 1628; dH (400 MHz, CDCl3) (cembrane ring numbering): 6.90 (1H, app. t, J
1.5, H-11), 6.33 (1H, br s, H-7), 6.14 (1H, br s, H-5), 5.10–5.03 (1H, m, H-10),
4.94–4.87 (2H, m, H-16), 4.29 (2H, app. d, J ꢀ3.0, H-19), 3.17 (1H, app. t, J ꢀ12,
H-9b), 2.87 (1H, dd, J 12.1 and 4.4, H-9
13b), 2.14–2.05 (1H, m, H-13
1.70–1.58 (2H, m, H-14b and CH2OH), 1.17 (1H, ddt, J 13.8, 3.3 and 0.8, H-14
a
), 2.64–2.33 (4H, m, H-2, H-1 and H-
), 1.94 (3H, br s, H-18), 1.75 (3H, br s, H-17),
);
a
a
dC (100 MHz, CDCl3): 174.5 (s), 151.9 (d), 150.6 (s), 149.3 (s), 145.4 (s), 132.9
(s), 129.1 (s), 117.6 (s), 117.6 (d), 116.0 (d), 113.1 (t), 79.6 (d), 68.3 (t), 43.4 (d),
35.9 (t). 31.2 (t), 30.6 (t), 20.1 (t), 19.2 (q), 9.6 (q); HRMS (ESI) 351.1566
(M+Na+, C20H24O4Na requires 351.1567).