Isobenzofuran Cycloaddition
2068±2071
1
Compound 3a: M.p. 235 ± 2408C (decomp); H NMR (300 MHz, CDCl
3
):
J.P. Mathias, A.M.Z. Slawin, D.R. Smith, J.F. Stoddart, D.J.
d 6.90 (m, 8H), 5.00 (brs, 4H), 3.00 (m, 4H), 2.87 (m, 4H), 2.53 (dt, J
Williams, J. Am. Chem. Soc. 1992, 114, 6330 ± 6353; c) J.Luo, H.
Hart, J. Org. Chem. 1987, 52, 4833 ± 4836; d) F.-G. Kl‰rner, J. Panitzky,
1
3
1
0.0, 2.2 Hz, 2H), 1.36 (m, 4H), 0.94 ppm (brd, 2H, J 10.0 Hz); C NMR
(
3
75 MHz, CDCl
3
) : d 209.9, 145.2, 126.5, 118.2, 82.56, 53.67, 43.77, 42.03,
D.Bl‰ser, R.Boese,
Tetrahedron 2001, 57, 3673 ± 3687; e) A.P.
4.15 ppm; MS: m/z: 477 [MH] , 459, 441, 293, 275, 183, 165; elemental
Marchand, J.M.Coxon, Acc. Chem. Res. 2002, 35, 271 ± 277; f) R.N.
Warrener, A.C.Schultz, D.N.Butler, S.D.Wang, I.B.Mahadevan,
R.A.Russell, Chem. Commun. 1997, 1023 ± 1024.
analysis calcd (%) for C32
H
28
O
4
: C 80.7, H 5.9; found: C 80.5, H 5.8.
1
Compound 3b: M.p. 207 ± 2108C (decomp); H NMR (300 MHz, CDCl
3
):
[
[
2] a) N.R.Lokan, M.N.Paddon-Row, M.Koeberg, J.W.Verhoeven,
Am. Chem. Soc. 2000, 122, 5075 ± 5081; b) V.Balaji, L.Ng, K .D .
Jordan, M.N.Paddon-Row, H.K.Patney, J. Am. Chem. Soc. 1987, 109,
6957 ± 6969.
J.
d 7.0 ± 7.40 (m, 8H), 5.17 (brs, 2H), 5.08 (dd, J 3.5, 2.0 Hz, 2H), 3.03 (m,
2
2
1
H), 2.91 (m, 2H), 2.87 (m, 2H), 2.68 (dt, J 10.3, 2.1 Hz, 1H), 2.29 (m,
H), 2.12 (m, 2H) 1.82 (m, 2H), 0.97 (dt, J 10.3, 1.3 Hz, 1H), 0.16 (dt, J
1
3
1.7 Hz, 1.3 Hz, 1H), À1.18 pp, (dt, J 11.7, 2.1 Hz, 1H); C NMR.
3] a) M.North, J. Peptide Science 2000, 6, 301 ± 313; b) I.G.Jones, W.
Jones, M.North, J. Org. Chem. 1998, 63, 1505 ± 1513.
(
75 MHz, CDCl
3
): d 209.4, 145.7, 144.4, 127.1, 126.6, 119.9, 118.9, 82.87,
8
1.16, 54.45, 53.73, 43.65, 41.99, 41.96, 37.98, 34.52, 31.93 ppm; MS: m/z: 494
[4] a) F.A.Khan, B.Prabhudas, J.Dash,
J. Prakt.Chem. 2000, 342, 512 ±
[
C
MNH
4
] , 477 [MH] , 459, 441, 359; elemental analysis calcd (%) for
5
2
5
17; b) G.Mehta, D .S .Reddy,
125 ± 2126; c) J.S.Yadav, P.K.Sasmal, Tetrahedron 1999, 55, 5185 ±
194.
J. Chem. Soc. Perkin Trans. 1 1998,
32
H
28
O
4
: C 80.7, H 5.9; found: C 80.7, H 6.0.
Compound 3c: 1H NMR (300 MHz, CDCl
H), 2.83 (m, 4H), 2.43 (m, 4H), 2.38 (m, 4H), 0.18 (brd, J 11.5 Hz, 2H),
): d 7.15 (m, 8H), 5.29 (m,
3
4
[
[
[
5] G.Mehta, S.Padma, J. Am. Chem. Soc. 1987, 109, 7230 ± 7232.
6] a) G.Mehta, R.Uma, Acc. Chem. Res. 2000, 33, 278 ± 286.
7] a) P.Yates, K.Switlak, Can. J. Chem. 1990, 68, 1894 ± 1900; b) M.C.
Carre nƒ o, R.J.L.Garcia, A.Urbano, M.A.Hoyos, J. Org. Chem. 1996,
1
3
À1.11 pp, (brd, J 11.5 Hz, 2H); C NMR (75 MHz, CDCl ): d 209.4,
3
1
44.3, 127.1, 119.8, 81.26, 54.40, 42.36, 38.14, 31.76 ppm; MS: m/z: 477
[
MH] , 459, 441.
Reduction of 3a: The diketone 3a (101 mg, 0.21 mmol) was refluxed with
LAH (100 mg, 2.5 mmol) in Na-dried tetrahydrofuran (5 mL) for 12 hours.
The reaction mixture was quenched (50 mL MeOH, water 30 mL), the
solvent was removed under reduced pressure, and the aqueous residue was
carefully acidified with hydrochloric acid (3m) to just below pH4 and
6
1, 2980 ± 2985.
8] W.Albrecht, Justus Liebigs Ann. Chem. 1906, 348, 31.
9] J.Meinwald, G .A .Wiley, J. Am. Chem. Soc. 1958, 80, 3667 ± 3671.
[
[
¹
[
10] AM1 minimized structures were calculated in Mopac 97 (Fujitsu
¹
Limited) implementation under ChemOffice2002 (Cambridge Soft
extracted with CH
filtered, and evaporated, and the residue was recrystallized from CH
pentane to yield 4 as colorless crystals (76 mg, 75%); H NMR (300 MHz,
2
Cl
2
(2 Â 100 mL).The extracts were dried (MgSO
4
),
Corporation, 100 Cambridge Park Drive, Cambridge, MA 02140).
2
Cl
2
/
¹
[
[
[
[
11] InsightII v.2000, 2002 Accelrys Inc.
1
12] B.Rickborn, Adv. Theor. InterestingMol. 1989, 1, 1 ± 134.
13] L.F.Fieser, M.J.Haddadin, Can. J. Chem. 1965, 43, 1599 ± 1606.
14] For a similar NMR assignment, see M.A.Makhlouf, B.Rickborn, J.
Org. Chem. 1981, 46, 2734 ± 2739.
15] This assignment, supported by COSY, NOESY, HMBC, and HMQC
data, contrasts with analogous systems for which opposite axial and
equatorial assignments are reported: a) M.P. Cava, F.M. Scheel, J.
Org. Chem. 1967, 32, 1304 ± 1307; b) K.Tori, K.Kitahonoki, Y .T akano,
H.Tanida, T.Tsuji, Tetrahedron Letters 1964, 5, 559 ± 564.
16] M J. .Stoermer, D C. .Chalmers, D P. .Fairlie, Royal Australian
Chemical Institute, Organic Division 16th National Conference,
Fairmont Resort, Leura, 1998.
CDCl
3
): d 7.07 (m, 8H), 4.97 (m, 4H), 4.28 (m, 2H), 3.18 (brs, 2H; OH),
2
0
1
.75 (m, 4H), 2.61 (dt, J 9.5, 2.2 Hz, 2H), 2.50 (m, 4H), 1.69 (m, 4H),
1
3
.93 ppm (brd, J 9.5 Hz, 2H); C NMR (75 MHz, CDCl ): d 146.5,
3
26.0, 118.4, 83.08, 70.87, 46.06, 44.78, 43.05, 37.97 ppm; MS: m/z: 481
[
[
MH] ; elemental analysis calcd (%) for C32
32 4
H O : C 80.0, H 6.7; found:
C 79.7, H 6.6.
Acknowledgement
[
We thank the Australian Research Council for initial funding for this work.
[
1] a) G.Mehta, J.Chandrasekhar,
Chem. Rev. 1999, 99, 1437 ± 1467;
b) P.R.Ashton, G.R.Brown, N.S.Isaacs, D.Giuffrida, F.H.Kohnke,
Received: November 28, 2002 [F4619]
Chem. Eur. J. 2003, 9, 2068 ± 2071
www.chemeurj.org
¹ 2003 Wiley-VCH Verlag GmbH & Co.KGaA, Weinheim
2071