Subscribe to RSS
DOI: 10.1055/s-0031-1290363
An Approach to exo-Enol Ether - Cyclic Ketal Structures Found in Marine Cembranoids, Based on Silver-Assisted Cyclisations of Enynone Precursors
Publication History
Publication Date:
24 February 2012 (online)
![](https://www.thieme-connect.de/media/synlett/201205/lookinside/thumbnails/10.1055-s-0031-1290363-1.jpg)
Abstract
Treatment of a solution of the (E)-enynone 17 in methanol with AgNO3 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.
Key words
enols - enynes - acetals - cyclisation - natural products
-
1a
Kamel HN.Ferreira D.Garcia-Fernandez LF.Slattery M. J. Nat. Prod. 2007, 70: 1223 -
1b
Venkateswarlu Y.Sridevi KV.Rama Rao M. J. Nat. Prod. 1999, 62: 756 -
1c
Epifánio R. de A.Maria LF.Fenical W. J. Braz. Chem. Soc. 2000, 11: 584 -
1d
Sánchez MC.Ortega MJ.Zubia E.Carballo JL. J. Nat. Prod. 2006, 69: 1749 -
1e
Grote D.Dahse H.-M.Seifert K. Chem. Biodiversity 2008, 5: 2449 - 2 For a recent summary, and speculations
on these biosynthetic interrelationships, see:
Yi L.Pattenden G. Nat. Prod. Rep. 2011, 28: 1269 - 3
Yi L.Pattenden G.Rogers J. Tetrahedron Lett. 2010, 51: 1280 - 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. -
5a
Saito S.Hasegawa T.Inaba N.Nishida R.Fujii T.Nomizu S.Muriwake T. Chem. Lett. 1984, 1389 -
5b
Doroh B.Sulikowski GA. Org. Lett. 2006, 8: 903 -
6a
Pattenden G.Winne JM. Tetrahedron Lett. 2009, 50: 7310 -
6b
Pattenden G.Winne JM. Tetrahedron Lett. 2010, 51: 5044 - 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
References and Notes
Aldehyde 16b
¹H
NMR (270 MHz, CDCl3): δ = 1.35 [3
H, s, CH
3C(OR)2CH3],
1.41 [3H, s, CH
3C(OR)2CH
3], 1.61
(3
H, s, CH
3COH), 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): δ = 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).
(
E
)-Enynone 17
¹H
NMR (400 MHz, CDCl3): δ = 1.31 (3 H,
t, J = 7.1 Hz, CO2CH2CH
3), 1.37 [3 H, s,
CH
3C(OR)2CH3],
1.42 [3 H, s, CH
3C(OR)2CH
3], 1.60 (3 H, s,
CH
3COH), 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, CO2CH
2CH3],
4.40-4.32 [1 H, m, CH(OR)],
6.80 (1 H, s, C=CH). ¹³C NMR
(100 MHz, CDCl3): δ = 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+]
(
E
)-Enynone 20
¹H
NMR (400 MHz, CDCl3): δ = 1.32 (3 H,
t, J = 7.1 Hz, CO2CH2CH
3), 1.62 (3 H, s, CH3COR),
1.73 [1 H, d(AB)d,
J = 13.1,
2.4 Hz, CH(OR)CH
eq
H],
1.85 [1 H, d(AB)d, J = 13.1,
11.8 Hz, CH(OR)CHH
ax
],
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, CO2CH
2CH3),
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): δ = 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 (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+].
Substituted Furan
25
Isolated as a ca. 3:2 mixture of E/Z-isomers.
¹H
NMR (400 MHz, CDCl3): δ [major isomer
(integrating for 60%)] = 1.35 [3
H, s, CH
3C(OR)2CH3],
1.35 (3 H, t, J = 7.1 Hz, CO2CH2CH
3], 1.44 [3
H, s, CH3C(OR)2CH
3],
1.87 (3 H, s, CH3C=C), 2.58-2.43 [2
H, m, CH(OR)CH
2],
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, CO2CH
2CH3), 6.60 (1
H, s, FurH); δ [minor isomer (integrating for
40%)] = 1.34 (3 H, t, J = 7.1
Hz, CO2CH2CH
3),
1.35 [3 H, s, CH
3C(OR)2CH3],
1.41 [3 H, s, CH3C(OR)2CH
3], 1.87 (3 H, s,
CH3C=C), 2.58-2.43 [2 H, m, CH(OR)CH
2], 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, CO2CH
2CH3), 6.69 (1
H, s, FurH). ¹³C NMR (HMQC-HMBC, 400
MHz, CDCl3): δ (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); δ (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+].
Enol Ether Cyclic
Ketal 28
Isolated as a 1:1 mixture of ketal epimers.
¹H
NMR (400 MHz, CDCl3): δ = 1.33 (3 H,
t, J = 7.1 Hz, CO2CH2CH
3), 1.48 [3 H, s,
CH
3C(OR)], 1.671
and 1.674 [1 H, 2 × ddd, J = 13.1, 11.9, 1.3 Hz, CH(OR)CH
ax
H],
1.73 and 1.74 [3 H, 2 × s, CH
3C(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)CHH
eq
],
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, CO2CH
2CH3), 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].
¹³C NMR + HMQC
(400 MHz, CDCl3): δ = 14.2 (CH3, 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): δ = 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): δ = 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+].
Substituted Furan 29
Isolated
as a ca. 3:2 mixture of E/Z-isomers.
¹H
NMR (400 MHz, CDCl3): δ [major isomer
(integrating for 58%)] = 1.356 (3 H,
t, J = 7.1 Hz, CO2CH2CH
3), 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, CO2CH
2CH3), 6.66 (1
H, s, FurH); δ [minor isomer (integrating for
42%)] = 1.359
(3 H, t, J = 7.1 Hz, CO2CH2CH
3), 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, CO2CH
2CH3), 6.63 (1 H,
s, FurH). ESI-MS: m/z calcd
for C15H22O6Na+:
321.1309; found: 321.1297 [MNa+].