Communications
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Scheme 3. Mechanistic explanation for the PdII-catalyzed heterocycliza-
tion/cross-coupling of a-allenols and protected a-allenols.
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active substrates, this is a potentially attractive method for
organic synthesis. Current work is aimed at exploring the
scope of the reaction with respect to both a-allenols and
protected a-allenols, and identifying applications in complex-
molecule synthesis.
Experimental Section
[5] a) B. Alcaide, P. Almendros, C. Aragoncillo, M. C. Redondo,
M. R. Torres, Chem. Eur. J. 2006, 12, 1539; b) B. Alcaide, P.
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G. Cabrero, M. P. Ruiz, Org. Lett. 2005, 7, 3981; f) B. Alcaide, P.
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[6] a) B. Alcaide, P. Almendros, C. Aragoncillo, M. C. Redondo, Eur.
J. Org. Chem. 2005, 98; b) B. Alcaide, P. Almendros, C.
Aragoncillo, Chem. Eur. J. 2002, 8, 1719; c) M. B. Isaac, T.-H.
Chan, J. Chem. Soc. Chem. Commun. 1995, 1003; the a-allenol
(À)-2g had been prepared previously as a mixture of regio- and
diastereoisomers by stannane chemistry: d) A. McCluskey, I. W.
Muderawan, Muntari, D. J. Young, J. Org. Chem. 2001, 66, 7811.
[7] Complete diastereoselectivity was observed in all cases except for
the reaction of the aldehyde (+)-1h.
[8] The configuration at the carbinol stereogenic center of the
enantiomerically pure a-allenols 2g–j was established by com-
parison of the 1H NMR chemical shifts of the corresponding
acetylmandelates according to the method developed by Trost
and co-workers: a) B. M. Trost, J. L. Belletire, S. Godleski, P. G.
McDougal, J. M. Balkovec, J. J. Baldwin, M. E. Christy, G. S.
Ponticello, S. L. Varga, J. P. Springer, J. Org. Chem. 1986, 51, 2370;
b) K. M. Sureshan, T. Miyasou, S. Miyamori, Y. Watanabe,
Tetrahedron: Asymmetry 2004, 15, 3357; for a review, see:
c) J. M. Seco, E. Quiꢁoꢂ, R. Riguera, Chem. Rev. 2004, 104, 17.
General procedure: PdCl2 (0.005 mmol) was added to a stirred
solution of an a-allenol 2 (0.10 mmol) and the appropriate protected
a-allenol 3 (0.30 mmol) in N,N-dimethylformamide (1.0 mL). The
reaction mixture was stirred under an argon atmosphere until the
starting material had disappeared (monitored by TLC). Water
(0.5 mL) was then added, and the reaction mixture was extracted
with ethyl acetate (3 4 mL). The organic phase was washed with
water (2 2mL), dried (MgSO ), and concentrated under reduced
4
pressure. Chromatography of the residue with mixtures of hexanes
and ethyl acetate as the eluent gave analytically pure 2,3,4-trisub-
stituted 2,5-dihydrofurans 4. (+)-4e: Prepared from (+)-2h (55 mg,
0.19 mmol); chromatographic purification of the crude product
(hexanes/ethyl acetate 20:1) gave (+)-4e (64 mg, 75%) as a colorless
oil; [a]D = + 45.5 (c = 2.1, CHCl3); 1H NMR (300 MHz, CDCl3,
258C): d = 7.48 (d, J = 9.0 Hz, 2H), 7.11 (d, J = 8.0 Hz, 2H), 6.97 (d,
J = 8.0 Hz, 2H), 6.79 (d, J = 9.0 Hz, 2H), 6.17 (br s, 1H), 5.28–5.30 (m,
1H), 5.21 (d, J = 1.2Hz, 1H), 4.72(d, J = 5.6 Hz, 1H), 4.67–4.69 (m,
2H), 4.58 (d, J = 1.2Hz, 1H), 4.55–4.57 (m, 1H), 3.67 (s, 3H), 3.65 (s,
3H), 2.33 (d, J = 0.7 Hz, 3H), 1.84 (d, J = 1.2Hz, 3H), 1.66–1.68 ppm
(m, 3H); 13C NMR (75 MHz, CDCl3, 2 58C): d = 164.9, 156.3, 144.2,
136.2, 135.9, 134.9, 134.5, 133.5, 130.4, 129.3, 129.1, 128.6, 118.9, 114.2,
114.1, 86.9, 82.7, 77.6, 61.7, 59.4, 55.3, 21.1, 15.1, 12.0 ppm; IR
(CHCl3): n˜ = 1742cm À1; MS (ESI): m/z (%): 446 (100) [M+H]+, 445
(11) [M]+; elemental analysis calcd (%) for C28H31NO4 (445.5): C
75.48, H 7.01, N 3.14; found: C 75.72, H 7.06, N 3.10.
Received: March 16, 2006
Published online: June 7, 2006
Keywords: allenes · cross-coupling · domino reactions ·
.
heterocycles · palladium
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2006, 45, 4501 –4504