COMMUNICATIONS
butyldiphenylsilyl ether 11 (99%), and reduction with
lithium borohydride, followed by an oxidative cleavage
with sodium periodate, afforded the aldehyde 12,[22]
which was oxidized to the corresponding acid 13 (90%
from 11). Subsequent esterification with trimethylsilyl-
diazomethane and deprotection of the silyl ether lead to
14 (14 A; 69%),[26] which is the C1 C9 subunit of
zincophorin.
The C1 C9 subunit of zincophorin has been synthe-
sized by an approach that involves three key steps: a
diastereoselective hydroboration of an optically en-
riched isopropenyl-cyclopropane, an anti-aldol conden-
sation, and a diastereoselective intramolecular oxy-
mercuration of a cyclopropylmethanol.
Received: February 25, 2002 [Z18771]
[1] Polyether Antibiotics, Vol. 1 and 2 (Ed.: J. W. Westley), Marcel
Dekker, New York, 1982.
[2] M. Dobler in Ionophores and their Structures, Wiley, New
York, 1981.
[3] H. A. Brooks, D. Gardner, J. P. Poyser, T. J. King, J. Antibiot.
1984, 37, 1501.
[4] U. Gr‰fe, W. Schade, M. Roth, L. Radics, M. Incze, K. Ujszaszy,
J. Antibiot. 1984, 37, 836.
[5] L. Radics, J. Chem. Soc. Chem. Commun. 1984, 599.
[6] U. Gr‰fe (Akademie der Wissenschaften der DDR), Ger.
(East) Patent, DD 231 793, 1986 [Chem. Abstr. 1987, 106,
101970].
[7] a) R. E. Zelle, M. P. DeNinno, H. G. Selnick, S. J. Danishefsky,
J. Org. Chem. 1986, 51, 5032; b) S. J. Danishefsky, H. G.
Selnick, R. E. Zelle, M. P. DeNinno, J. Am. Chem. Soc. 1988,
110, 4368.
[8] a) M. Balestra, M. D. Wittman, J. Kallmerten, Tetrahedron
Lett. 1988, 29, 6905; b) C. L. Cywin, J. Kallmerten, Tetrahedron
Lett. 1993, 34, 1103.
[9] J. A. Marshall, M. R. Palovich, J. Org. Chem. 1998, 63, 3701.
[10] S. R. Chemler, W. R. Roush, J. Org. Chem. 1998, 63, 3800.
[11] J. F. Booysen, C. W. Holzapfel, Synth. Commun. 1995, 25, 1473.
[12] S. D. Burke, R. A. Ng, J. A. Morrison, M. J. Alberti, J. Org.
Chem. 1998, 63, 3160.
Scheme 2. Synthesis of the C1 C9 subunit of zincophorin. a) BH3 ¥ THF/THF,
À308C !RT, then NaOH, H2O2; b) PCC, 4 ä molecular sieves, CH2Cl2, RT;
c) NaH, (EtO)2P(O)-CH2-COOEt, THF; d) H2, cat. PtO2, EtOAc, RT; e) DIBAL-
H, toluene, À788C; f) 6, EtNMe2, cHex2BCl, Et2O, 0 8C; add 5, À788C, 2 h and
À238C, 12 h, then MeOH, H2O2, pH 7buffer; g) HF ¥ pyridine, THF, RT;
h) Hg(OCOCF3)2, CH2Cl2, RT then KBr/H2O; i) nBu3SnH, toluene/THF,
RT !608C then CCl4; j) tBuPh2SiCl, imidazole, DMF, RT; k) LiBH4, THF,
À208C !RT then NaIO4, MeOH, RT; l) NaClO2, NaH2PO4, 2-methylbut-2-ene,
tBuOH/H2O, RT; m) Me3SiCHN2, MeOH/C6H6. R tBuPh2Si, Bz benzoyl.
[13] Y. Guindon, L. Murtagh, V. Caron, S. R. Landry, G. Jung, M.
¬
Bencheqroun, A.-M. Faucher, B. Guerin, J. Org. Chem. 2001,
66, 5427.
procedure (Hg(OCOCF3)2, CH2Cl2, RT, aqueous KBr work-
up), an extremely clean conversion to the organomercuric
bromide 9 was observed. The latter was not purified but
immediately subjected to reductive demercuration with
tributyltin hydride;[24] this lead to tetrahydropyran 10 in
85% yield and with a high diastereoselectivity (d.r. 93/
7).[25] The relative configuration of 10 indicates that the
[14] a) T. L. B. Boivin, Tetrahedron 1987, 43, 3309; b) G. Cardillo, M.
¡
Orena, Tetrahedron 1990, 46, 3321; c) J.-C. Harmange, B. Figadere,
Tetrahedron: Asymmetry 1993, 4, 1711.
[15] a) D. A. Evans, S. L. Bender, J. Morris, J. Am. Chem. Soc. 1988, 110,
2506; b) K. Bratt, A. Garavelas, P. Perlmutter, G. Westman, J. Org.
Chem. 1996, 61, 2109; for a related approach with allenes, see: c) R. D.
Walkup, G. Park, J. Am. Chem. Soc. 1990, 112, 1597; d) R. D. Walkup,
S. W. Kim, J. Org. Chem. 1994, 59, 3433.
[16] a) D. B. Collum, F. Mohamadi, J. S. Hallock, J. Am. Chem. Soc. 1983,
105, 6882; b) A. G. M. Barrett, W. Tam, J. Org. Chem. 1997, 62, 4653.
[17] For the synthesis of stereotriads involving an intramolecular oxy-
mercuration process, see: J. Cossy, N. Blanchard, C. Meyer, Org. Lett.
2001, 3, 2567.
[18] a) J. Cossy, N. Blanchard, C. Hamel, C. Meyer, J. Org. Chem. 1999, 64,
2608; b) J. Cossy, N. Blanchard, C. Meyer, Synthesis 1999, 1063.
[19] J. Cossy, N. Blanchard, C. Meyer, Eur. J. Org. Chem. 2001, 339.
[20] M. P. Doyle, R. E. Austin, A. S. Bailey, M. P. Dwyer, A. B. Dyatkin,
A. V. Kalinin, M. M. Y. Kwan, S. Liras, C. J. Oalmann, R. J. Pieters,
M. N. Protopopova, C. E. Raab, G. H. P. Roos, Q. L. Zhou, S. F.
Martin, J. Am. Chem. Soc. 1995, 117, 5763.
[21] The use of PCC or other oxidation procedures (Swern or Dess
Martin oxidations) afforded similar results and no alteration of the
diastereomeric purity of the aldehyde from 2 was detected.
intramolecular oxymercuration involved, as anticipated, an
[16, 17]
inversion of configuration at the C7atom.
The presence
of the silyl protecting group interferes with the intramolecular
oxymercuration of 7 (R tBuPh2Si), and implies additional
deprotection and protection steps. The corresponding benzyl
ether derivative was therefore synthesized (R CH2Ph), but
its intramolecular oxymercuration, followed by reductive
demercuration, proceeded in lower yield (46%) and diaster-
eoselectivity (d.r. 85/15) than for 8. Therefore, the presence
of the free alcohol at C9 was more appropriate for the
intramolecular oxymercuration step, and the synthesis of the
C1 C9 subunit of zincophorin was pursued from 10
(Scheme 2). The alcohol 10 was transformed to the tert-
Angew. Chem. Int. Ed. 2002, 41, No. 12
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