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Volumn 72, Issue 13, 2007, Pages 4611-4620

Indole diterpene synthetic studies: Development of a second-generation synthetic strategy for (+)-nodulisporic acids A and B

Author keywords

[No Author keywords available]

Indexed keywords

CROSS-COUPLING; FIRST-GENERATION APPROACH; INTERMEDIATES; NODULISPORIC ACIDS A;

EID: 34250895564     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo062423a     Document Type: Article
Times cited : (35)

References (54)
  • 16
    • 34250887578 scopus 로고    scopus 로고
    • Dankwardt and co-workers also examined the effect of the ring size on the mode of ring closure and therefore prepared an N-acryloyl-8- bromotetrahydroquinoline derivative upon Heck cyclization, and the ratio of the 5-exo-trig versus the 6-endo-trig products was reversed, favoring the former mode of cyclization. The authors concluded that the 6-endo-trig cyclization mode is only favored in systems (i.e, indoles and indolines) wherein the strain of the transition state would severely suppress the 5-exo- trig mode of ring closure
    • Dankwardt and co-workers also examined the effect of the ring size on the mode of ring closure and therefore prepared an N-acryloyl-8- bromotetrahydroquinoline derivative upon Heck cyclization, and the ratio of the 5-exo-trig versus the 6-endo-trig products was reversed, favoring the former mode of cyclization. The authors concluded that the 6-endo-trig cyclization mode is only favored in systems (i.e., indoles and indolines) wherein the strain of the transition state would severely suppress the 5-exo- trig mode of ring closure.
  • 17
    • 0030845067 scopus 로고    scopus 로고
    • For a few examples of radical or Pd-catalyzed cyclization of N-allyl-7-bromoindoles (Scheme 4), see: (a) Dobbs, A. P.; Jones, K.; Veal, K. T. Tetrahedron Lett. 1997, 38, 5379-5382.
    • For a few examples of radical or Pd-catalyzed cyclization of N-allyl-7-bromoindoles (Scheme 4), see: (a) Dobbs, A. P.; Jones, K.; Veal, K. T. Tetrahedron Lett. 1997, 38, 5379-5382.
  • 19
    • 34250870778 scopus 로고    scopus 로고
    • Intramolecular reactions between carbon-centered radicals and olefins prefer to proceed via a kinetic 5-exo-trig cyclization for stereoelectronic reasons. However, in the case of compound 17, only the corresponding 6-endo-trig cyclization product 19 was obtained along with some reduced product 20. Similar observations were obtained with the Pd-catalyzed cyclization of indole 21. The authors14 attributed the observed selectivity favoring the 6-endo-trig cyclization to the considerable strain and distortion in the transition state leading to the five-membered 1,7-annulated products, Chemical Equation Presented
    • 14 attributed the observed selectivity favoring the 6-endo-trig cyclization to the considerable strain and distortion in the transition state leading to the five-membered 1,7-annulated products. (Chemical Equation Presented)
  • 20
    • 34250852967 scopus 로고    scopus 로고
    • See Supporting Information
    • See Supporting Information.
  • 26
    • 0000010274 scopus 로고
    • Trost, B. M, Fleming, I, Eds, Pergamon: Oxford
    • Davis, D. R.; Garratt, P. J. In Comprehensive Organic Syntheses; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 2, pp 795-863.
    • (1991) Comprehensive Organic Syntheses , vol.2 , pp. 795-863
    • Davis, D.R.1    Garratt, P.J.2
  • 31
    • 34250889451 scopus 로고    scopus 로고
    • Generally, absolute ethanol at reflux is sufficient for the preparation of hydrazones; however, even after 12 h at reflux, we observed less than 5% of hydrazone 32, accompanied by significant decomposition of the hydrazine. Acetic acid was therefore added to catalyze the transformation.
    • Generally, absolute ethanol at reflux is sufficient for the preparation of hydrazones; however, even after 12 h at reflux, we observed less than 5% of hydrazone 32, accompanied by significant decomposition of the hydrazine. Acetic acid was therefore added to catalyze the transformation.
  • 38
    • 34250806627 scopus 로고    scopus 로고
    • The reaction was also found to be very sensitive to the anhydrous state of the NMP; that is, not sufficiently dried NMP caused the arylstannane 35 to undergo significant protodestannylation at the reaction temperature. The protodestannylation was found to be much faster than the cross-coupling; in some cases, no coupling product (40) was observed.
    • The reaction was also found to be very sensitive to the anhydrous state of the NMP; that is, not sufficiently dried NMP caused the arylstannane 35 to undergo significant protodestannylation at the reaction temperature. The protodestannylation was found to be much faster than the cross-coupling; in some cases, no coupling product (40) was observed.
  • 39
    • 0010521593 scopus 로고    scopus 로고
    • A survey of the literature revealed that this transformation might prove quite challenging since a mixture of 1,2- and 1,4-reduction products had been reported for many combination of enones and reducing agents: (a) Fortunato, J. M, Ganem, B. J. Org. Chem. 1976, 41, 2194-2200
    • A survey of the literature revealed that this transformation might prove quite challenging since a mixture of 1,2- and 1,4-reduction products had been reported for many combination of enones and reducing agents: (a) Fortunato, J. M.; Ganem, B. J. Org. Chem. 1976, 41, 2194-2200.
  • 50
    • 34250903652 scopus 로고    scopus 로고
    • Further increase in catalyst and ligand loadings did not result in higher yields of tetracyclic indole 45
    • Further increase in catalyst and ligand loadings did not result in higher yields of tetracyclic indole 45.
  • 54
    • 34250793991 scopus 로고    scopus 로고
    • When THF was used as the solvent, we isolated a side product in 10% yield in which the triflate functionality was reduced and the indoline ring was oxidized to the corresponding indole. This oxidation most likely occurred via air oxidation during the purification stage. However, we later found that, when THF was replaced with dioxane as the solvent, only the desired heptacyclic indole (+)-51 was obtained.
    • When THF was used as the solvent, we isolated a side product in 10% yield in which the triflate functionality was reduced and the indoline ring was oxidized to the corresponding indole. This oxidation most likely occurred via air oxidation during the purification stage. However, we later found that, when THF was replaced with dioxane as the solvent, only the desired heptacyclic indole (+)-51 was obtained.


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