Asymmetric Construction of Rings A−D of Daphnicyclidin-Type Alkaloids

Dunn, Travis B.; Ellis, J. Michael; Kofink, Christiane; Manning, James R.; Overman, Larry E.

doi:10.1021/ol902373m

Cited by 72 publications

(34 citation statements)

References 19 publications

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“…After the ketone was consumed, as judged by thin layer chromatography, 1.5 equiv of acetic acid were added to quench the excess organometallic reagent; allowing the reaction to then warm to −20 °C promoted lactonization to give pentacyclic lactone rac - 52 in 83% yield 51. The rate of vinylation was increased if 5 equiv of lithium chloride was added to the reaction mixture,52 however carbonate rac - 55 was then a significant byproduct ( rac - 52 : rac - 55 = 6:1). This byproduct was not observed when lithium chloride was absent.…”

Section: Resultsmentioning

confidence: 99%

Total Synthesis of (±)- and (−)-Actinophyllic Acid

2010

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Development of efficient sequences for the total syntheses of (±)-actinophyllic acid (rac-1) and (−)-actinophyllic acid (1) are described. The central step in these syntheses is the aza-Cope/Mannich reaction, which constructs the previously unknown hexacyclic ring system of actinophyllic acid in one step from much simpler tetracyclic precursors. The tetracyclic hexahydro-1,5-methano-1H-azocino [4,3-b]indole ketone rac-37 is assembled from o-nitrophenylacetic acid in four steps, with oxidative cyclization of a dienolate derivative of tricyclic precursor rac-35 being the central step. In the first-generation synthesis, this intermediate is transformed in two steps to homoallyl amine rac-43, whose formaldiminium derivative undergoes efficient aza-Cope/Mannich reaction to give pentacyclic ketone rac-44. In four additional steps, this intermediate is advanced to (±)-actinophyllic acid. The synthesis is streamlined by elaborating ketone rac-37 to β-hydroxyester intermediate rac-53, which is directly transformed to (±)-actinophyllic acid upon exposure to HCl and paraformaldehyde. This concise second-generation total synthesis of (±)-actinophyllic acid is realized in 22% overall yield from commercially available di-tert-butylmalonate and onitrophenylacetic acid by a sequence that proceeds by way of only six isolated intermediates. The first enantioselective total synthesis of (−)-actinophyllic acid (1) is accomplished by this direct sequence from tricyclic keto malonate (S)-35. Catalytic enantioselective reduction of α,β-unsaturated ketone 66 is the key step in the preparation of intermediate (S)-35 from the commercially available Boc-amino acid 65. Discussed also is the possibility that the aza-Cope/Mannich reaction might be involved in the biosynthesis of (−)-actinophyllic acid.

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Section: Resultsmentioning

confidence: 99%

Total Synthesis of (±)- and (−)-Actinophyllic Acid

2010

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“…The formation of both the monoaddition product and the unfavorable trans isomer was suppressed under these cerium-based carbonyl addition conditions. [16,17] The resultant diols were protected with MOM groups to give 1 a and 1 b in 74 % and 81 % overall yields, respectively, from 1,4-dihalobenzene. By using this method, we synthesized in total 50 g of the Lshaped monomers (1).…”

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Concise Synthesis and Crystal Structure of [12]Cycloparaphenylene

et al. 2011

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“…As significant homocoupling of the L-shaped diiodide was observed during the Pd-catalyzed synthesis of Ushaped unit, we changed our monomer unit to the corresponding dibromide 1 expecting high selectivity for crosscoupling. Accordingly, we developed a high-yielding synthesis of L-shaped dibromide 1: the addition of two equivalents of a 4-bromophenylcerium reagent [11] to cyclohexane-1,4-dione was followed by protection of the hydroxy groups with methoxymethyl (MOM) units (81 % overall yield of 1 from 1,4-dibromobenzene). Unlike our previous organolithium method, this Ce-based protocol provided the L-shaped unit with virtually complete cis stereoselectivity; the formation of the unfavorable trans isomer and the monoaddition product were both suppressed.…”

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confidence: 99%