Towards the total synthesis of desogestrel
Towards the total synthesis of desogestrel
Proposed is at total synthesis of the steroid desogestrel, utilizing a 1,4-addition/alkylation reaction to install the correct stereochemistry at C8, C13 and C14 in a single-pot operation as well as to domino reaction to construct the B and C-steroid rings in a single operation. Detailed is the synthesis of a number of 1,4-addition precursors including the optimization of an achiral Z-allylic phosphonate and the subsequent 1,4-addition reactions of these compounds. It was discovered that, whilst a Z-allylic phosphonate took part in the 1,4-addition/alkylation as expected, the reaction with the E-double bond isomer afforded a 2 : 1 mixture of the 1,4-addition/alkylation product : an intramolecular-cyclization bicyclic heptanone product. This intramolecular-cyclization reaction has plagued the 1,4-addition/alkylation reactions with phenyl allyl sulfoxide, and this discovery enabled the reaction to be conducted successfully within the allylic sulfoxide series by employing a Z-allylic sulfoxide. Also detailed are the subsequent reactions to convert the 1,4-addition/alkylation products into the domino cyclization precursors and the attempted domino reactions of these compounds. Whilst the domino reaction could not be realized, the C-ring cyclization was found to be extremely successful in the phosphonate series and subsequent optimization enabled yields of up to 92% to be obtained.
University of Southampton
Clarkson, Robert Aldous
9b1622b5-e239-4a8a-a60d-893f6f0f4604
2004
Clarkson, Robert Aldous
9b1622b5-e239-4a8a-a60d-893f6f0f4604
Clarkson, Robert Aldous
(2004)
Towards the total synthesis of desogestrel.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
Proposed is at total synthesis of the steroid desogestrel, utilizing a 1,4-addition/alkylation reaction to install the correct stereochemistry at C8, C13 and C14 in a single-pot operation as well as to domino reaction to construct the B and C-steroid rings in a single operation. Detailed is the synthesis of a number of 1,4-addition precursors including the optimization of an achiral Z-allylic phosphonate and the subsequent 1,4-addition reactions of these compounds. It was discovered that, whilst a Z-allylic phosphonate took part in the 1,4-addition/alkylation as expected, the reaction with the E-double bond isomer afforded a 2 : 1 mixture of the 1,4-addition/alkylation product : an intramolecular-cyclization bicyclic heptanone product. This intramolecular-cyclization reaction has plagued the 1,4-addition/alkylation reactions with phenyl allyl sulfoxide, and this discovery enabled the reaction to be conducted successfully within the allylic sulfoxide series by employing a Z-allylic sulfoxide. Also detailed are the subsequent reactions to convert the 1,4-addition/alkylation products into the domino cyclization precursors and the attempted domino reactions of these compounds. Whilst the domino reaction could not be realized, the C-ring cyclization was found to be extremely successful in the phosphonate series and subsequent optimization enabled yields of up to 92% to be obtained.
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Published date: 2004
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Local EPrints ID: 465436
URI: http://eprints.soton.ac.uk/id/eprint/465436
PURE UUID: a9650025-9b6e-4a0d-a8fa-5402a2929e16
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Date deposited: 05 Jul 2022 00:59
Last modified: 16 Mar 2024 20:10
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Author:
Robert Aldous Clarkson
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