An approach to exo-enol ether-cyclic ketal structures found in marine cembranoids, based on silver-assisted cyclisations of enynone precursors

Article abstract of DOI:10.1055/s-0031-1290363

Treatment of a solution of the (E)-enynone 17 in methanol with AgNO ₃ leads to cyclisation and isolation of the substituted furan 25 in >95% yield, rather than the anticipated exo-enol ether-cyclic ketal structure 24. By contrast, a similar Ag-mediated cyclisation of the related substituted enynone 20 led to the exo-enol ether-cyclic ketal structure 28 (50%) alongside the substituted furan 29 (45%). The outcomes of these silver-assisted enynone cyclisations are compared and contrasted with earlier studies with acid-catalysed reactions of furanoepoxides, for example 7, which also lead to exo-enol ether-cyclic ketals, viz. 1, and to substituted furanmethanol products, that is, 10. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0031-1290363

LETTER
723
An Approach to exo-Enol Ether – Cyclic Ketal Structures Found in Marine
Cembranoids, Based on Silver-Assisted Cyclisations of Enynone Precursors
S
ilver-Assisted E
n
e
ynone Cycl
r
isation
t
a
o
a
n
E
nol
E
l
ther–C
d
yclic
K
eta
l
Pattenden,* Johan M. Winne
School of Chemistry, The University of Nottingham, University Park, Nottingham, NG7 2RD, UK
Fax +44(115)9513535; E-mail: gp@nottingham.co.uk
Received 17 November 2011
CO2Me
OMe
Abstract: Treatment of a solution of the (E)-enynone 17 in metha-
nol with AgNO3 leads to cyclisation and isolation of the substituted
COR1
furan 25 in >95% yield, rather than the anticipated exo-enol ether–
cyclic ketal structure 24. By contrast, a similar Ag-mediated cycli-
sation of the related substituted enynone 20 led to the exo-enol
ether–cyclic ketal structure 28 (50%) alongside the substituted fu-
ran 29 (45%). The outcomes of these silver-assisted enynone cycli-
sations are compared and contrasted with earlier studies with acid-
catalysed reactions of furanoepoxides, for example 7, which also
lead to exo-enol ether–cyclic ketals, viz. 1, and to substituted furan-
methanol products, that is, 10.
OMe
R3
O
OAc
HO
O
HO
R2
O
O
1
R1 = H or OMe
CHO
OMe
2
CO2Me
OMe
Key words: enols, enynes, acetals, cyclisation, natural products
O
O
HO
HO
O
The interesting and unusual exo-enol ether–cyclic ketal
structural unit 1 is present in a number of cembranoid me-
tabolites, for example 2, 3, and 4, isolated from corals of
the genus Sinularia.1 In these corals the metabolites 2–4
are frequently found alongside furanmethanol and fura-
noepoxide – containing cembranoids, such as 5 and 6, re-
spectively (Figure 1).2
OAc
O
O
CO2Me
O
4
3
CHO
CO2Me
HO
3
3
7
7
O
O
O
OAc
HO
O
In earlier publications we have suggested that the structur-
al unit 1 found in the metabolites 2–4, most likely has its
origin in furan-containing congeners akin to 5 and 6, in-
volving acid-catalysed displacement reactions of their
oxy centres at C7 (cembranoid numbering) followed by
quenching the furanoxonium ion intermediates produced
in this manner with methanol (cf. structures 7, 8, and 9 in
Scheme 1).2 Using the epoxide 7 (R2 = R3 = Me) as a
model, we indeed found that its treatment with PTSA–
MeOH led to the enol ether–cyclic ketal 1 (R2 = R3 = Me).
Unfortunately, however, the structure 1 was unstable and
became rapidly isomerised under the reaction conditions
to its furanmethanol methyl ether positional isomer 10
(R2 = R3 = Me, Scheme 1).3
OAc
O
O
O
O
5
6
Figure 1 Structures of enol ether–cyclic ketal metabolites and their
congeners in Sinularia
CO2Me
R3
CO2Me
R3
HO
HO
O
O
O
R2
H+
R2
8
7
CO2Me
R3
H+
In this paper, we have examined an alternative perspective
on the relationship between the enol ether–cyclic ketal,
furanmethanol, and furanoepoxide structural units in the
metabolites 2–6, surmising that the furanoxonium ion in-
termediate 9 in Scheme 1 could be formed instead from
electrophilic activation of an acetylenic ketone precursor,
viz. 13.4 This acetylenic ketone 13 is related to the vinyl
carbocation species 14 and also to enedione compounds,
viz. 12, which can be produced in vivo by sequential oxi-
O
+
HO
MeOH
R2
MeOH
CO2Me
9
CO2Me
OMe
R3
MeO
R3
O
O
1
R2
R2
HO
HO
10
SYNLETT 2012, 23, 723–726
Advanced online publication: 24.02.2012
DOI: 10.1055/s-0031-1290363; Art ID: D68211ST
x
x.
x
x.
2
0
1
2
Scheme 1 Acid-catalyzed transformations of epoxyfurans to enol
ether–cyclic ketals and furanmethanol derivatives
© Georg Thieme Verlag Stuttgart · New York

724
G. Pattenden, J. M. Winne
LETTER
CO2Me
R3
CO2Me
[O]
id, followed by separation of 17 from its Z-isomer formed
concurrently by chromatography (Scheme 3).6,7 The p-
methoxy-benzylidene acetal 20, corresponding to 17, was
synthesised starting from the diastereoisomer 18 of 16a,
which, by straightforward treatment with p-methoxybenz-
aldehyde dimethylacetal in the presence of camphorsul-
fonic acid, first gave 19a. Oxidation of 19a with MnO2
and a Knoevenagel condensation of the resulting aldehyde
19b with ethyl acetoacetate, followed by chromatogra-
phy, then gave the benzylidene acetal substituted (E)-
enynone 20.8
R3
H2O
O
O
O
R2
HO R2
11
12
CO2Me
R3
CO2Me
R3
H+
+
O
O
R2
HO
14
13
HO
R2
A number of electrophilic reagents have been used to ac-
tivate acetylene-containing compounds as a prelude to
their capture and cyclisation with proximal oxy function-
alities.9 We were attracted to examining the cyclisations
of the (E)-enynone compounds 17 and 20 in the presence
of Ag(I) in the form of silver nitrate. Thus, when a solu-
tion of the (E)-enynone 17 in dry methanol was stirred in
the presence of anhydrous AgNO3 for five minutes, work-
up and chromatography gave a single cyclic product, con-
taining an incorporated OMe substituent, in almost
quantitative yield. The spectroscopic data for the new
compound, however, were not consistent for those of the
expected exo-enol ether–cyclic ketal product 24. Instead,
the spectroscopic data correlated with the furan structure
25 where the incorporated OMe substituent forms part of
a different enol ether unit (Scheme 4).10 The structure 25,
which was produced as a 3:2 mixture of Z- and E-isomers,
is most likely derived from the enynone 17 via initial for-
mation of the oxonium ion intermediate 21. Addition of
methanol to 21 would be expected to next lead to the
equilibrating silver-bound intermediates 22 and 23. Proto-
nation of the sp2 carbon-to-silver bond in 22 would then
lead to the enol ether–cyclic ketal 24, whereas protonation
of the tertiary alcohol centre in 23 accompanied by elimi-
nation would give the substituted furan 25. Presumably
the elimination reaction from 23 is much faster than the
protonation of 22, which explains why the substituted fu-
ran 25 is produced exclusively and at the expense of 24.
In support of the foregoing proposal, treatment of the
enynone 20 containing a benzylidene acetal unit at C7 (cf.
17) with silver nitrate gave the anticipated exo-enol ether–
cyclic ketal structure 28 alongside the furan structure 29
related to 25 (Scheme 5).11 We presume that in this con-
version, elimination from the silver-bound intermediate
27 (cf. 23) producing 29 is retarded by the bulky ben-
zylidene acetal substituent, thereby allowing the accumu-
lation of the enol ether–cyclic ketal 28 from the
equilibrating silver complex 26. This rationale is also in
accord with the observation that the cyclisation of 17 to 25
is complete within minutes, whereas the cyclisation of 20
to 28/29 takes more than 12 hours.
CO2Me
R3
MeOH
1
O
+
R2
HO
9
Scheme 2 Proposed mode of cyclisation of (E)-enynones to enol
ether–cyclic ketals
dative cleavage and hydrolysis of alkenylfuran-containing
precursors, that is, 11 (Scheme 2).2
To examine the feasibility of the synthesis of exo-enol
ether–cyclic ketals, viz. 1, from electrophilic activation of
acetylenic ketones of constitution 13, we synthesised the
substrates 17 and 20. The substituted (E)-enynone 17 was
smoothly prepared from the known methyl ketone 155 fol-
lowing: i) addition of the bisanion of propargyl alcohol
and separation of the diastereoisomer 16a of the resulting
tert-alcohol by chromatography; ii) oxidation of 16a to
the corresponding aldehyde 16b, using MnO2 in CH2Cl2,6
and iii) a Knoevenagel condensation between 16b and
ethyl acetoacetate in the presence of piperidine–acetic ac-
CO2Et
R
O
O
O
i
iii
HO
HO
O
O
O
O
O
15
17
16a, R = CH2OH
16b, R = CHO
ii
CO2Et
R
R
O
iv
iii
HO
O
O
O
O
O
OH
O
OH
Ar
ii
Ar
18
R = CH2OH
20
19a, R = CH2OH
19b, R = CHO
In conclusion, we have shown that solutions of appropri-
ately functionalised (E)-enynones in methanol undergo
cyclisation in the presence of AgNO3 leading to enol
ether–cyclic ketal structures, for example 28, similar to
those present in cembranoids metabolites isolated from
corals, cf. 2, 3, and 4.4 This investigation therefore com-
Scheme 3 Synthesis of the substituted (E)-enynones 17 and 20.
Reagents and conditions: i, HOCH2CCH, BuLi, THF, –40 °C to r.t.,
37% (16a) + 31% (18); ii, MnO2, CH2Cl2, 25 °C, 69% (16b), 65%
(19b); iii, MeCOCH2CO2Et, piperidine, AcOH, THF, 25 °C, chroma-
tographic separation of E-isomers, 30% (17), 21% (20); iv,
ArCH(OMe)2, CSA, CH2Cl2, 0–25 °C, 78% (Ar = 4-MeOC6H4).
Synlett 2012, 23, 723–726
© Thieme Stuttgart · New York

LETTER
Silver-Assisted Enynone Cyclisation to an Enol Ether–Cyclic Ketal
725
CO2Et
References and Notes
(1) (a) Kamel, H. N.; Ferreira, D.; Garcia-Fernandez, L. F.;
Ag
HO
AgNO3
Slattery, M. J. Nat. Prod. 2007, 70, 1223.
O
17
(b) Venkateswarlu, Y.; Sridevi, K. V.; Rama Rao, M. J. Nat.
Prod. 1999, 62, 756. (c) Epifánio, R. de A.; Maria, L. F.;
Fenical, W. J. Braz. Chem. Soc. 2000, 11, 584. (d)Sánchez,
M. C.; Ortega, M. J.; Zubia, E.; Carballo, J. L. J. Nat. Prod.
2006, 69, 1749. (e) Grote, D.; Dahse, H.-M.; Seifert, K.
Chem. Biodiversity 2008, 5, 2449.
O
MeOH
25 °C
O
MeOH
OMe
21
H+
Ag
CO2Et
OMe
CO2Et
(2) For a recent summary, and speculations on these
biosynthetic interrelationships, see: Yi, L.; Pattenden, G.
Nat. Prod. Rep. 2011, 28, 1269.
Ag
HO
H+
O
O
HO
O
O
(3) Yi, L.; Pattenden, G.; Rogers, J. Tetrahedron Lett. 2010, 51,
1280.
O
O
23
(4) Related exo-enol ether spiroketal metabolites have been
isolated alongside polyacetylenic compounds, from
compositae, and it is believed that the two families are
related biosynthetically, see: Bohlmann, F.; Burkhardt, T.;
Zdero, C. Naturally Occurring Acetylenes; Academic Press:
London/New York, 1973.
22
X
CO2Et
CO2Et
OMe
MeO
(5) (a) Saito, S.; Hasegawa, T.; Inaba, N.; Nishida, R.; Fujii, T.;
Nomizu, S.; Muriwake, T. Chem. Lett. 1984, 1389.
(b) Doroh, B.; Sulikowski, G. A. Org. Lett. 2006, 8, 903.
(6) (a) Pattenden, G.; Winne, J. M. Tetrahedron Lett. 2009, 50,
7310. (b) Pattenden, G.; Winne, J. M. Tetrahedron Lett.
2010, 51, 5044.
O
O
HO
O
O
O
O
24 (not observed)
25 (E/Z mixture)
(7) Aldehyde 16b
Scheme 4 Rationalisation of the formation of the furan 25 from the
(E)-enynone 17 in the presence of AgNO3
1H NMR (270 MHz, CDCl3): d = 1.35 [3 H, s,
CH3C(OR)2CH3], 1.41 [3H, s, CH3C(OR)2CH3], 1.61
(3 H, s, CH3COH), 1.96 [1 H, d(AB)d, J = 14.1, 5.5 Hz,
CH(OR)CHHC], 2.15 [1 H, d(AB)d, J = 14.1, 7.2 Hz,
CH(OR)CHHC], 3.47 [1 H,(br) s, OH], 3.64 (1 H, dd,
J = 8.2, 7.0 Hz, CHHOR], 4.14 [1 H, dd, J = 8.2, 6.0 Hz,
CHHOR], 4.38 [1 H, (app. t)(app. t), J = 7.2, 7.0, 6.0, 5.5 Hz,
CH(OR)], 9.22 (1 H, s, CHO). 13C NMR (67 MHz, CDCl3):
d = 25.8 (CH3), 26.8 (CH3), 29.5 (CH3), 45.3 (CH2), 67.0 (C),
69.9 (CH2), 72.9 (CH), 81.2 (C), 98.8 (C), 109.3 (C), 176.8
(CH).
CO2Et
CO2Et
H+
OMe
OMe
Ag
O
Ag
O
AgNO3
O
O
20
MeOH
25 °C
Ar
Ar
O
OH
O
OH
H+
26
27
(E)-Enynone 17
1H NMR (400 MHz, CDCl3): d = 1.31 (3 H, t, J = 7.1 Hz,
CO2CH2CH3), 1.37 [3 H, s, CH3C(OR)2CH3], 1.42 [3 H, s,
CH3C(OR)2CH3], 1.60 (3 H, s, CH3COH), 1.96 [1 H,
d(AB)d, J = 14.1, 5.5 Hz, CH(OR)CHH], 2.13 [1 H, d(AB)d,
J = 14.1, 7.0 Hz, CH(OR)CHH], 2.44 (3 H, s, CH3CO), 2.96
[1 H,(br) s, OH), 3.65 (1 H, dd, J = 8.2, 7.5 Hz, CHHOR],
4.14 (1 H, dd, J = 8.2, 6.0 Hz, CHHOR), 4.27 [2 H, q, J = 7.1
Hz, CO2CH2CH3], 4.40–4.32 [1 H, m, CH(OR)], 6.80 (1 H,
s, C=CH). 13C NMR (100 MHz, CDCl3): d = 14.1 (CH3),
25.8 (CH3), 26.8 (CH3), 29.9 (CH3), 30.4 (CH3), 45.4 (CH2),
61.8 (CH2), 67.5 (C), 69.9 (CH2), 73.1 (CH), 79.0 (C), 108.2
(C), 109.1 (C), 122.5 (CH), 143.0 (C), 163.7 (C), 198.5 (C).
ESI-MS: m/z calcd for C17H24O6Na+: 347.1465; found:
347.1472 [MNa+]
CO2Et
CO2Et
OMe
MeO
O
O
O
Ar
HO
OH
O
OH
28 (50%)
29 (45%, E/Z mixture)
Scheme 5 Formation of the exo-enol ether–cyclic ketal 28 from
Ag(I)-assisted cyclisation of the (E)-enynone 20 (Ar = 4-MeOC6H4)
plements earlier work where the same exo-enol ether–
cyclic ketal structures were derived from acid-catalysed
reactions with furanoepoxides (Scheme 1).1 However,
these studies, taken together, highlight the sensitivity of
the same exo-enol ether–cyclic ketal structures in vitro
and their propensity for rearrangement and isomerisation
to their more stable furan positional isomers, cf. structures
1 and 10, 24 and 25, also 28 and 29.
(8) (E)-Enynone 20
1H NMR (400 MHz, CDCl3): d = 1.32 (3 H, t, J = 7.1 Hz,
CO2CH2CH3), 1.62 (3 H, s, CH3COR), 1.73 [1 H, d(AB)d,
J = 13.1, 2.4 Hz, CH(OR)CHeqH], 1.85 [1 H, d(AB)d, J =
13.1, 11.8 Hz, CH(OR)CHHax], 2.03 [1 H,(br) s, OH], 2.45
(3 H, s, CH3CO), 3.63 [1 H, d(AB)d(br), J = 11.9, 5.8 Hz,
CHCHHOH], 3.74 [1 H, d(AB)(app. t)(br), J = 11.9, ca. 3
Hz, CHCHHOH], 3.80 [3 H,(br) s, CH3OAr), 4.17–4.24 [1
H, m, CH(OR)], 4.30 (2 H, q, J = 7.1 Hz, CO2CH2CH3), 5.93
[1 H, s, ArCH(OR)2], 6.84 (1 H, s, C=CH), 6.90 [2 H,
d(AA¢XX ¢), J = 8.7 Hz, ArH), 7.46 [2 H, d(AA¢XX ¢), J =
8.7 Hz, ArH]. 13C NMR (100 MHz, CDCl3): d = 14.2 (CH3),
29.3 (CH3), 30.4 (CH3), 38.2 (CH2), 55.3 (CH2), 61.9 (CH3),
65.3 (CH2), 70.8 (C), 74.6 (CH), 82.5 (C), 97.4 (CH), 106.0
Acknowledgment
We thank the EPSRC for funding to support Johan Winne.
© Thieme Stuttgart · New York
Synlett 2012, 23, 723–726

726
G. Pattenden, J. M. Winne
LETTER
13C NMR + HMQC (400 MHz, CDCl3): d = 14.2 (CH3,
(C), 113.7 (2 CH), 122.3 (CH), 127.8 (2 CH), 130.5 (C),
143.0 (C), 160.2 (C), 165.3 (C), 193.6 (C). ESI-MS: m/z
calcd for C22H26O7Na+: 425.1571; found: 425.1566 [MNa+].
1.33), 24.4 and 24.6 (CH3, 1.73 and 1.74), 29.3 (CH3, 1.48),
36.0 (CH2, 1.67, 1.73, 1.74), 50.57 and 50.62 (CH3, 3.13 and
3.16), 55.3 (CH3, 3.80), 61.0 (CH2, 4.29), 65.9 (CH2, 3.61–
3.73), 75.08 and 75.13 (CH, 3.96–4.03), 75.34 and 75.36
(C), 96.53 and 96.56 (CH, 5.72 and 5.73), 110.17 and 110.21
(CH, 4.89 and 4.91), 113.7 (2 CH, 6.90), 114.2 (C), 127.6 (2
CH, 7.44), 131.3 (C), 134.3 and 134.4 (C), 137.4 and 137.5
(CH, 7.02 and 7.03), 153.25 and 153.32 (C), 160.0 (C),
161.8 (C). 1H NMR + HMBC (400 MHz, CDCl3): d = 1.33
(61.0), 1.48 (36.0, 75.4, 110.2), 1.67 (29.3, 65.9, 75.1, 75.3,
110.2), 1.73 and 1.74 (50.6, 114.2, 134.3 and 134.4), 1.99
(–), 2.33 and 2.39 (75.1, 75.3), 3.13 and 3.16 (114.2), 3.61–
3.73 (75.1), 3.80 (160.0), 3.96–4.03 (–), 4.29 (14.2, 161.8),
4.89 and 4.91 (29.3, 36.0, 137.4 and 137.5, 153.3), 5.72 and
5.73 (75.1, 127.5), 6.90 (113.7, 131.3, 160.0), 7.02 and 7.03
(114.2, 153.3, 161.8), 7.44 (96.5, 113.7, 127.5, 160.0). 1H
NMR + COSY (400 MHz, CDCl3): d = 1.33 (4.29), 1.48
(–), 1.67 (2.33 and 2.39, 3.96–4.03, 4.89 and 4.91), 1.73 and
1.74 [7.02 and 7.03 (w)], 1.99 (3.61–3.73), 2.33 and 2.39
(1.67, 3.96–4.03), 3.13 and 3.16 (–), 3.61–3.73 (1.99, 3.96–
4.03), 3.80 (6.90), 3.96–4.03 (1.67, 2.33 and 2.39, 3.61–
3.73), 4.29 (1.33), 4.89 and 4.91 (1.67, 7.02 and 7.03), 5.72
and 5.73 (7.44), 6.90 (3.80, 7.44), 7.02 and 7.03 [4.89 and
4.91, 1.73 and 1.74 (w)], 7.44 (5.72 and 5.73, 7.44). ESI-MS:
m/z calcd for C23H30O8Na+: 457.1824; found: 457.1833
[MNa+].
(9) For a recent study with 1-alkynyl-2-carbonyl quinoline
substrates, see: Godet, T.; Vaxelaine, C.; Michel, C.; Milet,
A.; Belmont, P. Chem. Eur. J. 2007, 13, 5632; and
references cited therein.
(10) Substituted Furan 25
Isolated as a ca. 3:2 mixture of E/Z-isomers.
1H NMR (400 MHz, CDCl3): d [major isomer (integrating
for 60%)] = 1.35 [3 H, s, CH3C(OR)2CH3], 1.35 (3 H, t, J =
7.1 Hz, CO2CH2CH3], 1.44 [3 H, s, CH3C(OR)2CH3], 1.87 (3
H, s, CH3C=C), 2.58–2.43 [2 H, m, CH(OR)CH2], 2.60 (3 H,
s, FurCH3), 3.46 (3 H, s, CH3O), 3.65 (1 H, app. t, J = 8.1,
ca. 7 Hz, CHHOR), 4.05 (1 H, dd, J = 8.1, 6.0 Hz, CHHOR),
4.20–4.26 [1 H, m, CH(OR)], 4.29 (2 H, q, J = 7.1 Hz,
CO2CH2CH3), 6.60 (1 H, s, FurH); d [minor isomer
(integrating for 40%)] = 1.34 (3 H, t, J = 7.1 Hz,
CO2CH2CH3), 1.35 [3 H, s, CH3C(OR)2CH3], 1.41 [3 H, s,
CH3C(OR)2CH3], 1.87 (3 H, s, CH3C=C), 2.58–2.43 [2 H, m,
CH(OR)CH2], 2.59 (3 H, s, FurCH3), 3.47 (3 H, s, CH3O),
3.53 (1 H, app. t, J = 8.1, ca. 7 Hz, CHHOR), 4.01 (1 H, dd,
J = 8.1, 6.0 Hz, CHHOR), 4.20–4.26 [1 H, m, CH(OR)], 4.29
(2 H, q, J = 7.1 Hz, CO2CH2CH3), 6.69 (1 H, s, FurH). 13
C
NMR (HMQC-HMBC, 400 MHz, CDCl3): d (major isomer)
= 13.9 (CH3), 14.4 (CH3), 18.0 (CH3), 25.7 (CH3), 26.9
(CH3), 35.9 (CH2), 58.5 (CH3), 60.1 (CH2), 69.5 (CH2), 74.9
(CH), 108.7 (C), 111.4 (CH), 114.4 (C), 120.0 (C), 141.8
(C), 146.7 (C), 158.4 (C), 163.9 (C); d (minor isomer) = 13.9
(CH3), 14.4 (CH3), 16.2 (CH3), 25.7 (CH3), 26.8 (CH3), 36.6
(CH2), 58.3 (CH3), 60.1 (CH2), 69.1 (CH2), 74.9 (CH), 108.9
(C), 111.1 (CH), 114.4 (C), 120.5 (C), 142.3 (C), 146.6 (C),
158.7 (C), 163.9 (C). ESI-MS: m/z calcd for C18H26O6Na+:
361.1622; found: 361.1618 [MNa+].
Substituted Furan 29
Isolated as a ca. 3:2 mixture of E/Z-isomers.
1H NMR (400 MHz, CDCl3): d [major isomer (integrating
for 58%)] = 1.356 (3 H, t, J = 7.1 Hz, CO2CH2CH3), 1.88
(3 H, s, CH3C=C), 2.05 [1 H,(br)s, CHOH), 2.29 (1 H, s,
CH2OH), 2.31 (1 H, dd, J = 13.8, 5.2 Hz, =CCHH), 2.49 (1
H, dd, J = 13.8, 8.6 Hz, =CCHH), 2.59 (3 H, s, FurCH3), 3.46
(1 H,(br) dd, J = 11.5, 6.5 Hz, CHHOH), 3.478 (3 H, s,
CH3O), 3.62–3.68 (1 H, m, CHHOH), 3.84–3.93 (1 H, m,
CHOH), 4.298 (2 H, q, J = 7.1 Hz, CO2CH2CH3), 6.66 (1 H,
s, FurH); d [minor isomer (integrating for 42%)] = 1.359
(3 H, t, J = 7.1 Hz, CO2CH2CH3), 1.86 (3 H, s, CH3C=C),
2.29 (1 H, s, CH2OH), 2.36 [1 H, d(AB)d, J = 13.1, 5.8 Hz,
=CCHH], 2.51 [1 H, d(AB)d, J = 13.1, 8.1 Hz, =CCHH],
2.56 [1 H, d(br), J = 5.3 Hz, CHOH], 2.61 (3 H, s, FurCH3),
3.55 [1 H,(br) d(app. t), J = 11.2, 4.6 Hz, CHHOH), 3.481 (3
H, s, CH3O), 3.62–3.68 (1 H, m, CHHOH), 3.84–3.93 (1 H,
m, CHOH), 4.303 (2 H, q, J = 7.1 Hz, CO2CH2CH3), 6.63 (1
H, s, FurH). ESI-MS: m/z calcd for C15H22O6Na+: 321.1309;
found: 321.1297 [MNa+].
(11) Enol Ether Cyclic Ketal 28
Isolated as a 1:1 mixture of ketal epimers.
1H NMR (400 MHz, CDCl3): d = 1.33 (3 H, t, J = 7.1 Hz,
CO2CH2CH3), 1.48 [3 H, s, CH3C(OR)], 1.671 and 1.674 [1
H, 2 × ddd, J = 13.1, 11.9, 1.3 Hz, CH(OR)CHaxH], 1.73 and
1.74 [3 H, 2 × s, CH3C(OCH3)], 1.99 [1 H,(br) dd, J = 7.7,
5.3 Hz, OH], 2.33 and 2.39 [1 H, 2 × dd, J = 13.1, 2.1 Hz,
CH(OR)CHHeq], 3.13 and 3.16 (3 H, 2 × s, CH3OCOR),
3.61–3.73 (2 H, m, CH2OH), 3.80 (3 H, s, CH3OAr), 3.96–
4.03 [1 H, m, CH(OR)CH2OH], 4.29 (2 H, q, J = 7.1 Hz,
CO2CH2CH3), 4.89 and 4.91 [1 H, 2 × d, J = 1.3 Hz,
CH=C(OR)], 5.72 and 5.73 [1 H, 2 × s, ArCH(OR)2], 6.90 [2
H, d(AA¢XX ¢), J = 8.6 Hz, ArH], 7.02 and 7.03 (1 H, 2 × s,
CH=CCO2R), 7.44 [2 H, d(AA¢XX ¢), J = 8.6 Hz, ArH].
Synlett 2012, 23, 723–726
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