• DOI:10.1021/JO9603789
• Corpus ID: 2723479

An Efficient Bidirectional Approach to the C(2)-Symmetric Stereoisomers of the Bistetrahydrofuran Core of the Acetogenins.

@article{Marshall1996AnEB,
  title={An Efficient Bidirectional Approach to the C(2)-Symmetric Stereoisomers of the Bistetrahydrofuran Core of the Acetogenins.},
  author={James A. Marshall and Kevin W. Hinkle},
  journal={The Journal of organic chemistry},
  year={1996},
  volume={61 13},
  pages={
          4247-4251
        }
}

• J. A. Marshall, K. Hinkle
• Published 26 June 1996
• Chemistry
• The Journal of organic chemistry

A bidirectional route to nonracemic C(2)-symmetric bistetrahydrofuran units related to acetogenin natural products was developed starting from the (S,S)-tartrate-derived dialdehyde 3.3. Bis-homologation with the (R)-alpha-OMOM crotylstannane (R)-4.1 in the presence of InCl(3) afforded the anti adduct, diol 4.3. The derived tosylate 4.4, upon treatment with TBAF in THF, underwent sequential TBS cleavage and cyclization to the (R,R,R,R,R,R)-bis-OMOM bistetrahydrofuran 4.7. The epimeric (S,R,R,R,R,S)-bis-OMOM bistetrahydrofuran 4.10 was prepared along similar lines, except that the (R)-alpha-OMOM crotylstannane (R)-4.1 was first converted to the (R)-gamma-isomer (R)-4.2 with BF(3).OEt(2). Subsequent addition of dialdehyde 3.3 led to the diol adduct 4.5, which after tosylation and treatment with TBAF, yielded the bistetrahydrofuran 4.10. By repeating the aforementioned sequences, but starting with the (S)-alpha-OMOM-crotylstannane (S)-4.1, the (S,S,R,R,S,S)- and the (R,S,R,R,S,R)-bistetrahydrofurans 5.5 and 5.8 were prepared. A variation on the foregoing sequence in which the OTBS grouping of the adduct was converted to a mesylate and the OH group was used to effect intramolecular displacement was also examined. Accordingly, adduct ent-5.3 from BF(3)-promoted addition of stannane (R)-4.2 and ent-3.3, the enantiomer of aldehyde 3.3, was acetylated. Cleavage of the TBS ether followed by mesylate formation and then concommitant acetate hydrolysis and cyclization with methanolic Triton B yielded the bis-OMOM bistetrahydrofuran 5.5. An analogous sequence was used to convert adduct 4.3 to ent-4.10. In this case, acetate saponification was effected with methanolic K(2)CO(3), and the resulting diol, 7.4, was cyclized with NaH in THF.