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Step-efficient asymmetric approaches to saturated nitrogen heterocycles

Step-efficient asymmetric approaches to saturated nitrogen heterocycles
Step-efficient asymmetric approaches to saturated nitrogen heterocycles
An imino-aldol reaction between phenyl chlorovalerate and a variety of (S)-tert butylsulfinimines was developed which gave consistently high diastereoselectivites of up to 95:5:0:0 dr and yields of up to 87%. In several cases, single crystal X-ray crystallography confirmed the stereochemistry of the major products to be syn. Successful isolation of these syn imino-aldol products allowed them to be converted to a variety of enantiopure saturated nitrogen heterocycles. Natural products (–)-epilupinine ((–)-1.71) and (–)-tashiromine ((–)-1.72) were successfully synthesised in enantiopure form in 6 steps from chloroalkanoic acid phenyl esters via this highly stereoselective imino-aldol reaction with 19 and 12% overall yield respectively. Absolute stereochemical determination of the minor anti imino-aldol product was possible through its use in the synthesis of (+)-lupinine ((+)-1.70). A new synthetic route towards the synthesis of (+)-allomatrine ((+)-1.121) was devised and investigated. The key imino-aldol step was not very selective however, as such this approach was abandoned and was not investigated further due to time constraints. Finally a range of piperidine analogues was synthesised from a variety of imino-aldol products produced using our reaction conditions. These confirmed the stereochemistry of the major diastereomers as being syn, demonstrating both the reliability of these reaction conditions, and the effectiveness of using the imino-aldol reaction as the key step in this short route to enantiopure saturated nitrogen heterocycles.
Cutter, Amanda C.
695ec27a-ac9d-425a-b74b-65045e3a9927
Cutter, Amanda C.
695ec27a-ac9d-425a-b74b-65045e3a9927
Brown, Richard
21ce697a-7c3a-480e-919f-429a3d8550f5

(2012) Step-efficient asymmetric approaches to saturated nitrogen heterocycles. University of Southampton, Chemistry, Doctoral Thesis, 198pp.

Record type: Thesis (Doctoral)

Abstract

An imino-aldol reaction between phenyl chlorovalerate and a variety of (S)-tert butylsulfinimines was developed which gave consistently high diastereoselectivites of up to 95:5:0:0 dr and yields of up to 87%. In several cases, single crystal X-ray crystallography confirmed the stereochemistry of the major products to be syn. Successful isolation of these syn imino-aldol products allowed them to be converted to a variety of enantiopure saturated nitrogen heterocycles. Natural products (–)-epilupinine ((–)-1.71) and (–)-tashiromine ((–)-1.72) were successfully synthesised in enantiopure form in 6 steps from chloroalkanoic acid phenyl esters via this highly stereoselective imino-aldol reaction with 19 and 12% overall yield respectively. Absolute stereochemical determination of the minor anti imino-aldol product was possible through its use in the synthesis of (+)-lupinine ((+)-1.70). A new synthetic route towards the synthesis of (+)-allomatrine ((+)-1.121) was devised and investigated. The key imino-aldol step was not very selective however, as such this approach was abandoned and was not investigated further due to time constraints. Finally a range of piperidine analogues was synthesised from a variety of imino-aldol products produced using our reaction conditions. These confirmed the stereochemistry of the major diastereomers as being syn, demonstrating both the reliability of these reaction conditions, and the effectiveness of using the imino-aldol reaction as the key step in this short route to enantiopure saturated nitrogen heterocycles.

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Published date: 30 September 2012
Organisations: University of Southampton, Chemistry

Identifiers

Local EPrints ID: 354552
URI: http://eprints.soton.ac.uk/id/eprint/354552
PURE UUID: 2a30647f-deec-42f1-9171-abf89f68e9cf
ORCID for Richard Brown: ORCID iD orcid.org/0000-0003-0156-7087

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Date deposited: 21 Oct 2013 14:31
Last modified: 06 Jun 2018 13:01

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