Total Synthesis of Dehaloperophoramidine : Evolution of a Synthesis
(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.
(Less)
- author
- Danielsson, Jakob LU ; Popov, Kirill LU ; Seashore-Ludlow, Brinton and Somfai, Peter LU
- organization
- publishing date
- 2017
- type
- Chapter in Book/Report/Conference proceeding
- publication status
- published
- subject
- keywords
- Cascade reactions, Diels–Alder reactions, Domino reactions, Indole alkaloids, Palladium, Total synthesis
- host publication
- Strategies and Tactics in Organic Synthesis
- series title
- 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
- 2022-03-09 08:12:02
@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}},
booktitle = {{Strategies and Tactics in Organic Synthesis}},
issn = {{1874-6004}},
keywords = {{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}},
doi = {{10.1016/B978-0-12-811790-3.00008-0}},
volume = {{13}},
year = {{2017}},
}