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Synlett 2012(5): 723-726  
DOI: 10.1055/s-0031-1290363
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

An Approach to exo-Enol Ether - Cyclic Ketal Structures Found in Marine Cembranoids, Based on Silver-Assisted Cyclisations of Enynone Precursors

Gerald 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;
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Publication History

Received 17 November 2011
Publication Date:
24 February 2012 (online)

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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

    References and Notes

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  • 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. 
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7

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+]

8

( 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+].

10

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+].

11

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+].