References
1
Li YS.
Matsunaga K.
Ishibashi M.
Ohizumi Y.
J. Org. Chem.
2001,
66:
2165
2
Garlaschelli L.
Vidari G.
Zanoni G.
Tetrahedron
1992,
48:
9495
3a This step is related to the proposed biosynthesis of the iridoids; for a review of iridoid chemistry, including biosynthetic aspects, see: El-Naggar LJ.
Beal JL.
J. Nat. Prod.
1980,
43:
649
3b For a pioneering total synthesis based on this mode of dialdehyde cyclisation see: Büchi G.
Gubler B.
Schneider RS.
Wild J.
J. Am. Chem. Soc.
1967,
89:
2776
4
Ménard M.
DPhil Thesis
Oxford;
UK:
2003.
5
Curran DP.
Chang CT.
J. Org. Chem.
1989,
54:
3140
6
Forbes JE.
Tailhan C.
Zard SZ.
Tetrahedron Lett.
1990,
31:
2565
7
Ollivier C.
Bark T.
Renaud P.
Synthesis
2000,
1598
8a
Doyle MP.
Dyatkin AB.
Kalinin AV.
Ruppar DA.
Martin SF.
Spaller MR.
Liras S.
J. Am. Chem. Soc.
1995,
117:
11021
8b
Ali SM.
Chapleo CB.
Finch MAW.
Roberts SM.
Woolley GT.
Cave RJ.
Newton RF.
J. Chem. Soc., Perkin Trans. 1
1980,
2093
9
Bertrand F.
Quiclet-Sire B.
Zard SZ.
Angew. Chem. Int. Ed.
1999,
38:
1943
10 DLP (100 mg, 0.25 mmol) was added every 2 h (3×) to a solution of iodide 8 (750 mg, 2.98 mmol) in dry chlorobenzene (40 mL) at 95 °C. After 7 h in total, a solution of ethyl 2-phenylvinyl sulfone
[15]
(1.75 g, 8.93 mmol) in chlorobenzene (5 mL) was added and the reaction mixture was heated at 145 °C. tert-Butyl peroxide was added every 2 h (3 × 100 µL) and the solution was heated at 145 °C for 16 h. The cooled solution was poured directly onto the top of a silica gel column, and the column was flushed with petroleum ether to remove chlorobenzene. Elution was then continued with a 4:1 mixture of petroleum ether-EtOAc to afford lactone 18 (390 mg, 57%) as colourless crystals after recrystallisation from Et2O. R
f
= 0.42 (3:1 petroleum ether-EtOAc); mp 76-81 °C. IR (KBr disc): νmax = 2971 (m), 1779 (s), 1493 (w), 1448 (w), 1421 (w), 1357 (w), 1299 (w), 1248 (w), 1176 (s), 1042 (s), 974 (s), 898 (w), 752 (m), 696 (m) cm-1. 1H NMR (400 MHz, CDCl3): δ = 1.57-1.66 (1 H, m), 1.93-2.01 (1 H, m), 2.04-2.11 (1 H, m), 2.23-2.31 (1 H, m), 2.42-2.50 (1 H, m), 2.44 (1 H, dd, J = 18.8, 1.4 Hz), 2.57 (1 H, br q, apparent J = 8.0 Hz), 2.76 (1 H, dd, J = 18.8, 8.8 Hz), 4.99-5.08 (1 H, m), 6.08 (1 H, dd, J = 15.6, 7.6 Hz), 6.44 (1 H, d, J = 15.6), 7.21-7.36 (5 H, m, Ph). 13C NMR (100.6 MHz, CDCl3): δ = 32.0, 34.1, 45.7, 49.6, 77.2, 85.8, 126.1, 127.5, 128.6, 130.6, 130.8, 136.8, 176.9. MS (CI, NH3): m/z (%) = 246 (100) [MNH4
+], 229 (25) [MH+], 169 (10), 87 (20), 70 (20). HRMS (CI): m/z calcd for C15H20NO2 [MNH4
+]: 246.1494; found: 246.1491.
11 Compounds analogous to lactone 21 that lack oxygen-containing functionality in the cyclopentane ring (cf. the dioxolane in 21) exist, in general, as tautomeric mixtures. Spectroscopic data for 21: R
f
= 0.35 (EtOAc); mp 81-84 °C. IR (KBr disc): νmax = 2967 (s), 2883 (m), 2740 (s), 1718 (s), 1682 (s), 1618 (s), 1420 (s), 1373 (m), 1198 (s), 1128 (s), 1074 (s), 1014 (s), 966 (m), 943 (m) cm-1. 1H NMR (500 MHz, CDCl3): δ = 1.51-1.63 (1 H, m), 1.68-1.80 (1 H, m), 2.01-2.10 (1 H, m), 2.24-2.39 (2 H, m), 3.27 (1 H, ddd, J = 9.1, 6.8, 2.3 Hz), 3.95-4.03 and 4.09-4.16 (4 H, m), 4.86-4.93 (1 H, m) overlaying 4.89 (1 H, d, J = 5.2 Hz), 7.44 (1 H, dd, J = 14.1, 2.3 Hz), 9.13 (1 H, d, J = 14.1 Hz). 13C NMR (125.7 MHz, CDCl3): δ = 27.0, 33.5, 39.1, 49.0, 65.0, 65.1, 82.3, 105.6, 105.9, 154.6, 172.8. HRMS (ES): m/z calcd for C11H13O5 [M - H]: 225.0763; found: 225.0754. NOE experiment: Irradiation of the enolic hydroxyl proton at δ = 9.13 ppm led to enhancement of the resonances at δ = 3.27 (-CHC=), 3.95-4.03 and 4.09-4.16 (-OC2H4O-), 4.89
[-CH(OR)2], and 7.44 (=CHOH) ppm; irradiation of the olefinic proton at δ = 7.44 ppm led only to an enhancement at δ = 9.13 (=CHOH) ppm.
12 Conditions attempted: CSA, THF; HCl, THF; HCl, acetone; TsOH, MeOH; BF3·OEt2, CD2Cl2; Dowex, MeOH; CSA, CD3OD. For further details, see ref. 4
13
Stork G.
Sher PM.
J. Am. Chem. Soc.
1983,
105:
6765
14 For example: Larock RC.
Lee NH.
J. Am. Chem. Soc.
1991,
113:
7815
15
Truce WE.
Goralski CT.
J. Org. Chem.
1971,
36:
2536
