Intramolecular allenolate acylations in studies toward a synthesis of FR182877

Organic Letters

Volumn 3, Issue 26, 2001, Pages 4307-4310

  Vanderwal, Christopher D ^a   Vosburg, David A ^a   Sorensen, Erik J ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALLENOLIC ACID; ANTINEOPLASTIC AGENT; FR 182877; NAPHTHALENE DERIVATIVE; POLYCYCLIC HYDROCARBON;

ACYLATION; ARTICLE; CHEMICAL STRUCTURE; CHEMISTRY; SYNTHESIS;

ACYLATION; ANTINEOPLASTIC AGENTS; MOLECULAR STRUCTURE; NAPHTHALENES; POLYCYCLIC COMPOUNDS;

EID: 0035961039     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol016994v     Document Type: Article

References (44)

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5. Reference 1 details a sequence of type I intramolecular Diels-Alder, ring-closing Knoevenagel and transannular hetero Diels-Alder reactions. We note that an alternative order in which a structure of type 4 undergoes a ring-closing Knoevenagel condensation followed by two sequential transannular Diels-Alder reactions is also appealing from both biogenetic and synthetic standpoints.
6. For a review of the Diels-Alder reaction in polyketide natural product biosynthesis, see: Ichihara, A.; Oikawa, H. In Comprehensive Natural Products Chemistry; Barton, D. H. R., Nakanishi, K., Meth-Cohn, O., Eds.; Elsevier: New York, 1999; Vol. 5, p 367.
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10. c (reference b). Macquarimicin A (5) is nonetheless depicted in Figure 1 as it was originally disclosed.
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23. Macromodel MM2 calculations predict that the desired E-alkylidene 3 is 5.5 kcal/mol more stable than Z-alkylidene 21. It was hoped that the build-up of strain in the transition state for the allenolate acylation may favor a stereospecific acylation to deliver the desired E-product.
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33. Though very susceptible to protodestannylation, dienylstannane 15 can be purified by rapid filtration through a short plug of basic alumina. The instability of 2-substituted-1-stannyl-1,3-dienes has been documented. For an example, see: Uenishi, J.; Kawahama, R.; Tanio, A.; Wakabayashi, S. J. Chem. Soc., Chem. Commun. 1993, 1438.
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35. The stannylation/Stille two-step reaction sequence could be performed on 20 mmol scale.
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37. The use of various catalysts, apolar solvents, and/or alternative diol protecting groups shifted the diastereomeric ratio in favor of the undesired endo cycloadduct.
38. Removal of steric crowding in the vicinity of the aldehyde carbonyl was a prerequisite for ring-forming bond constructions.
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40. Our preliminary experiments suggest that this reductive acylation method may not be general.
41. Examination of molecular models suggests that the geometrical requirements for acylation are satisfied only when the allenolate configuration is S as shown in 22.
42. We were not able to isomerize 20 or 21 to the desired E geometry. We could not induce formation of the desired E-alkylidene geometry by altering reaction temperature, solvent, and reducing agent.
43. The synthesis of 21 proceeds in 8.3% yield over 18 steps from 12, and as such, gram quantities of 21 should be readily available.
44. 3, δ): compound 11, acyclic: 8.15; compound 20, 12-membered ring: 7.45; macquarimicin A (5), 10-membered ring: 6.77; cochleamycin A (6), 10-membered ring: 6.78.