Angewandte
Chemie
Keywords: kinetic resolution · natural products · oxidation ·
.
tetrahydrofurans · tetrahydropyrans
[1] J. Hartung, M. Greb, J. Organomet. Chem. 2002, 661, 67 – 84.
[2] M. M. Faul, B. E. Huff, Chem. Rev. 2000, 100, 2407 – 2473.
[3] a) J. Hartung, P. Schmidt, Synlett 2000, 367 – 370; b) J. Hartung,
S. Drees, M. Greb, P. Schmidt, I. Svoboda, H. Fuess, A. Murso, D.
Stalke, Eur. J. Org. Chem. 2003, 2388 – 2408; c) J. Hartung, Pure.
Appl. Chem. 2005, 77, 1559 – 1576.
[4] W. Zhang, A. Basak, Y. Kosugi, Y. Hoshino, H. Yamamoto,
Angew. Chem. 2005, 117, 4363 – 4365; Angew. Chem. Int. Ed.
2005, 44, 4389 – 4391.
[5] The reaction of racemic bishomoallylic alcohol 1 was carried out
under the conditions of Hartung([VO(O iPr)3], CHCl3, TBHP
(1.1 equiv), RT, ligand L1 (10 mol% )), and s = 1.3 was
measured:
s = krel(fast/slow) = ln[(1ꢁc)(1ꢁee)]/ln[(1ꢁc)(1+ee)]:
“Kinetic Resolution”: H. B. Kagan, J. C. Fiaud in Topics in
Stereochemistry, Vol. 18 (Eds.: E. L. Eliel, S. H. Wilen), Wiley,
1988, pp. 249 – 330.
[6] A. T. Radosevich, C. Musich, F. D. Toste, J. Am. Chem. Soc.
2005, 127, 1090 – 1091.
[7] See the SupportingInformation.
[8] Only trisubstituted olefins gave promising results under these
conditions; substrates containingdisubstituted alkenes gave only
minor amounts of cyclic products, and only alcohol oxidation
was observed even usingCHCl 3/TBHP.
[9] Reported yields were calculated for racemic alcohols before the
resolution (i.e., highest theoretical yield = 50%).
[10] E. D. Mihelich, K. Daniels, D. J. Eickhoff, J. Am. Chem. Soc.
1981, 103, 7690 – 7692.
[11] H. Mimoun, M. Mignard, P. Brechot, L. Saussine, J. Am. Chem.
Soc. 1986, 108, 3711 – 3718.
[12] D. Rehder, Coord. Chem. Rev. 1999, 182, 297 – 322.
[13] Kennedy oxidative cyclizations generally provide trans-substi-
tuted THFs: a) S. Tang, R. M. Kennedy, Tetrahedron Lett. 1992,
33, 5303 – 5306; for exceptions, see: b) S. C. Sinha, A. Sinha, S. C.
Sinha, E. Keinan, J. Am. Chem. Soc. 1997, 119, 12014 – 12015;
c) Y. Morimoto, T. Iwai, J. Am. Chem. Soc. 1998, 120, 1633 –
1634.
Scheme 3. Synthesis of (ꢁ)-pantofuranoid E. Reagents and conditions:
a) TBSOTf, 2,6-lutidine, CH2Cl2, 08C, 30 min (95%); b) Me-
(MeO)NH·HCl, MeMgBr (2 equiv); then MeMgBr excess, THF,
ꢁ788C, 2 h (76%); c) lithium trimethylsilylacetylide, CeCl3, Et2O/Et3N
(1:1), ꢁ788C, 4 h; then K2CO3, MeOH, RT, 1 h (60%, d.r.=4:1);
d) nBu3SnH, [PdCl2(PPh3)2], CH2Cl2, 08C!RT, 30 min (82%); e) NBS,
CH2Cl2, 08C, 1 h (87%); f) TBAF, THF, RT, 1 h (94%). Tf=triflate.
installation of vinyl bromide was achieved in two steps from
16: first palladium-catalyzed hydrostannation[18] of the alkyne
was carried out (82% yield) followed by tin/bromide
exchange with N-bromosuccinimide (NBS; 87% yield).
Deprotection of the TBS group with tetrabutylammonium
fluoride (TBAF) gave (ꢁ)-pantofuranoid E in 94% yield.
Notably, this total synthesis and X-ray structural studies
allowed the assignment of the absolute configuration of
pantofuranoid E.
In conclusion, we have developed a highly diastereo- and
enantioselective synthesis of 2,5-trans-THPs and 2,4-cis-THFs
usingsequential resolution/oxidative cyclization of racemic
bis- and homoallylic a-hydroxyesters. Both steps in the
reaction sequence are catalyzed by a vanadium(v)–oxo
complex with a readily available tridentate Schiff base
ligand. Additionally, the reversed diastereoselectivity
observed in the formation of 2,5-trans-THPs and 2,4-cis-
THFs is attributed to chelation of the ester carbonyl group to
the Lewis acidic vanadium catalyst duringthe epoxidation
event. This synthetic method provides an efficient asymmetric
synthesis of cyclic ethers, as demonstrated by an expeditious
enantioselective synthesis of (ꢁ)-pantofuranoid E.
[14] Reversal in selectivity has also been observed for the titanium-
catalyzed epoxidation of homoallylic a-amino alcohols, see: A.
´
Krasinski, J. Jurczak, Tetrahedron: Asymmetry 2002, 13, 2075 –
2078.
[15] M. Cueto, J. Darias, Tetrahedron 1996, 52, 5899 – 5906.
[16] J. M. Williams, R. B. Jobson, N. Yasuda, G. Marchesini, U.-H.
Dolling, E. J. J. Grabowski, Tetrahedron Lett. 1995, 36, 5461 –
5464.
[17] a) M. E. Jung, J. Pontillo, J. Org. Chem. 2002, 67, 6848 – 6851;
b) E. M. Carreira, J. Du Bois, Tetrahedron Lett. 1995, 36, 1209 –
1212.
[18] B. M. Trost, Z. T. Ball, Synthesis 2005, 853 – 887.
Received: October 31, 2005
Published online: February 27, 2006
Angew. Chem. Int. Ed. 2006, 45, 2096 –2099
ꢀ 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim