A new method for the synthesis of spiroacetals and synthesis studies towards (+)-phyllanthocin
A new method for the synthesis of spiroacetals and synthesis studies towards (+)-phyllanthocin
A new method for the synthesis of spiroacetals is presented involving the facile addition of a stannyl radical to an appropriate triple bond and subsequent 5-exo-trig-cyclisation onto a suitable double bond. The requisite alkyne was synthesised by the addition of lithium acetylide to a lactone, followed by coupling of the lactol formed to an allylic alcohol. Radical cyclisation, using tri-n-butyltin hydride, was followed by protodestannylation, best effected by n-butyllithium. Several 6,5-spiroacetal systems were formed via this methodology, including the 6,5,6-ring system that forms the basic skeleton of (+ )-phyllanthocin. A synthetic strategy for (+ )-phyllanthocin, using the above methodology, is presented, requiring the synthesis of a lactone, (4S, 5R)-4-hydroxy-5-methyl-2H-pyran-2-one, and an allylic alcohol, methyl (3R)-hydroxycyclohex-4-en-1S-carboxylate. Attempts to make the requisite lactone using the radical cyclisation of 1-(2-bromo-2-propenyl)-2-benzyloxypropenoate only yielded the reduced analogue. However, the aldol coupling of methyl acetate with (R)-3-[(tert-butyldimethylsilyl)oxy]-2-methylpropan-1-al, then fluoride induced desilylation and ring closure gave the required lactone as a 1:1 mixture of epimers at the 4-hydroxy position. A synthetic route to the desired alcohol and a procedure to complete the synthesis is proposed.
University of Southampton
1992
Biggs, Karen Ruth
(1992)
A new method for the synthesis of spiroacetals and synthesis studies towards (+)-phyllanthocin.
University of Southampton, Doctoral Thesis.
Record type:
Thesis
(Doctoral)
Abstract
A new method for the synthesis of spiroacetals is presented involving the facile addition of a stannyl radical to an appropriate triple bond and subsequent 5-exo-trig-cyclisation onto a suitable double bond. The requisite alkyne was synthesised by the addition of lithium acetylide to a lactone, followed by coupling of the lactol formed to an allylic alcohol. Radical cyclisation, using tri-n-butyltin hydride, was followed by protodestannylation, best effected by n-butyllithium. Several 6,5-spiroacetal systems were formed via this methodology, including the 6,5,6-ring system that forms the basic skeleton of (+ )-phyllanthocin. A synthetic strategy for (+ )-phyllanthocin, using the above methodology, is presented, requiring the synthesis of a lactone, (4S, 5R)-4-hydroxy-5-methyl-2H-pyran-2-one, and an allylic alcohol, methyl (3R)-hydroxycyclohex-4-en-1S-carboxylate. Attempts to make the requisite lactone using the radical cyclisation of 1-(2-bromo-2-propenyl)-2-benzyloxypropenoate only yielded the reduced analogue. However, the aldol coupling of methyl acetate with (R)-3-[(tert-butyldimethylsilyl)oxy]-2-methylpropan-1-al, then fluoride induced desilylation and ring closure gave the required lactone as a 1:1 mixture of epimers at the 4-hydroxy position. A synthetic route to the desired alcohol and a procedure to complete the synthesis is proposed.
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Published date: 1992
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Local EPrints ID: 461255
URI: http://eprints.soton.ac.uk/id/eprint/461255
PURE UUID: 66c6a63d-73c8-4942-895f-de13c39d3f1a
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Date deposited: 04 Jul 2022 18:41
Last modified: 04 Jul 2022 18:41
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Author:
Karen Ruth Biggs
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