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Total Synthesis of Dehaloperophoramidine : Evolution of a Synthesis

Danielsson, Jakob LU ; Popov, Kirill LU ; Seashore-Ludlow, Brinton and Somfai, Peter LU (2017) In Strategies and Tactics in Organic Synthesis 13. p.217-242
Abstract

This account describes our efforts toward developing a stereodivergent entry to perophoramidine and the communesin alkaloids. The original approach toward our simplified model substrates relied on a palladium-catalyzed carbopalladation–carbonylation of a tetrasubstituted olefin to install the vicinal all-carbon quaternary stereocenters present in the target molecules, the olefin's stereochemistry thus dictating the relative stereochemistry of the quaternary stereocenters. Although the carbonylation–carbopalladation sequence worked well for trisubstituted olefins, only premature esterification was observed when using tetrasubstituted alkene substrates. Our second approach made use of the latent symmetry embedded in our target molecules.... (More)

This account describes our efforts toward developing a stereodivergent entry to perophoramidine and the communesin alkaloids. The original approach toward our simplified model substrates relied on a palladium-catalyzed carbopalladation–carbonylation of a tetrasubstituted olefin to install the vicinal all-carbon quaternary stereocenters present in the target molecules, the olefin's stereochemistry thus dictating the relative stereochemistry of the quaternary stereocenters. Although the carbonylation–carbopalladation sequence worked well for trisubstituted olefins, only premature esterification was observed when using tetrasubstituted alkene substrates. Our second approach made use of the latent symmetry embedded in our target molecules. A Diels–Alder reaction or SmI2-mediated bis-alkylation of isoindigo was to be used to access the communesin and perophoramidine scaffolds, respectively. We found that due to unfavorable thermodynamics, it was not possible to reach the communesin scaffold. However, two new complexity-generating, cascade reactions were encountered en route to the synthesis of dehaloperophoramidine, resulting in a short and efficient synthesis.

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author
organization
publishing date
type
Chapter in Book/Report/Conference proceeding
publication status
published
subject
keywords
Cascade reactions, Diels–Alder reactions, Domino reactions, Indole alkaloids, Palladium, Total synthesis
in
Strategies and Tactics in Organic Synthesis
volume
13
pages
26 pages
publisher
Academic Press
external identifiers
  • scopus:85037049701
ISSN
1874-6004
DOI
10.1016/B978-0-12-811790-3.00008-0
language
English
LU publication?
yes
id
cdb70462-aaff-4dd4-90c5-9423ec92bcbd
date added to LUP
2018-01-02 11:45:26
date last changed
2018-01-02 11:45:26
@inbook{cdb70462-aaff-4dd4-90c5-9423ec92bcbd,
  abstract     = {<p>This account describes our efforts toward developing a stereodivergent entry to perophoramidine and the communesin alkaloids. The original approach toward our simplified model substrates relied on a palladium-catalyzed carbopalladation–carbonylation of a tetrasubstituted olefin to install the vicinal all-carbon quaternary stereocenters present in the target molecules, the olefin's stereochemistry thus dictating the relative stereochemistry of the quaternary stereocenters. Although the carbonylation–carbopalladation sequence worked well for trisubstituted olefins, only premature esterification was observed when using tetrasubstituted alkene substrates. Our second approach made use of the latent symmetry embedded in our target molecules. A Diels–Alder reaction or SmI<sub>2</sub>-mediated bis-alkylation of isoindigo was to be used to access the communesin and perophoramidine scaffolds, respectively. We found that due to unfavorable thermodynamics, it was not possible to reach the communesin scaffold. However, two new complexity-generating, cascade reactions were encountered en route to the synthesis of dehaloperophoramidine, resulting in a short and efficient synthesis.</p>},
  author       = {Danielsson, Jakob and Popov, Kirill and Seashore-Ludlow, Brinton and Somfai, Peter},
  issn         = {1874-6004},
  keyword      = {Cascade reactions,Diels–Alder reactions,Domino reactions,Indole alkaloids,Palladium,Total synthesis},
  language     = {eng},
  pages        = {217--242},
  publisher    = {Academic Press},
  series       = {Strategies and Tactics in Organic Synthesis},
  title        = {Total Synthesis of Dehaloperophoramidine : Evolution of a Synthesis},
  url          = {http://dx.doi.org/10.1016/B978-0-12-811790-3.00008-0},
  volume       = {13},
  year         = {2017},
}