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The synthesis and resolution of a new chiral auxiliary and its application in asymmetric dihydroxylation & The first total synthesis of (+)-allomatrine and other lupin alkaloids

The synthesis and resolution of a new chiral auxiliary and its application in asymmetric dihydroxylation & The first total synthesis of (+)-allomatrine and other lupin alkaloids
The synthesis and resolution of a new chiral auxiliary and its application in asymmetric dihydroxylation & The first total synthesis of (+)-allomatrine and other lupin alkaloids
The synthesis and resolution of a new chiral auxiliary; trans-2-tritylcyclohexanol (1.15) is described allowing access to either enantiomer in gram quantities in excellent enantiomeric purity; (?)-1.15 in >99% ee and (+)-1.15 in 97% ee. Our new chiral controller (1.15) was subsequently applied to the diastereoselective osmium catalysed dihydroxylation of its 2-substituted acrylate ester derivatives. (±)-1.15 exhibited improved selectivity over other chiral auxiliary controlled dihydroxylations of substituted acrylate esters. In addition, the first total synthesis of the tetracyclic lupin alkaloid (+)-allomatrine (5.01) has been completed in 6% yield over 12 steps. This was followed by a second generation synthesis improving on our previous efforts; increasing the overall yield to 14%. The target molecule was assembled with excellent control of four contiguous stereocentres employing a diastereoselective imino-aldol reaction, ring-closing metathesis and an N-acyliminium cyclisation as key transformations. As part of our studies towards (+)-allomatrine (5.01) we performed the first total synthesis of the unnatural isomeric tricyclic alkaloid; (?)-lamprolobine (6.14) and bicyclic lupin alkaloid (?)-epilupinine (5.62).
Watkin, Samuel
2c7bcee4-92a8-4be8-af0d-7621245472c9
Watkin, Samuel
2c7bcee4-92a8-4be8-af0d-7621245472c9
Brown, Richard
21ce697a-7c3a-480e-919f-429a3d8550f5

(2013) The synthesis and resolution of a new chiral auxiliary and its application in asymmetric dihydroxylation & The first total synthesis of (+)-allomatrine and other lupin alkaloids. University of Southampton, Chemistry, Doctoral Thesis, 226pp.

Record type: Thesis (Doctoral)

Abstract

The synthesis and resolution of a new chiral auxiliary; trans-2-tritylcyclohexanol (1.15) is described allowing access to either enantiomer in gram quantities in excellent enantiomeric purity; (?)-1.15 in >99% ee and (+)-1.15 in 97% ee. Our new chiral controller (1.15) was subsequently applied to the diastereoselective osmium catalysed dihydroxylation of its 2-substituted acrylate ester derivatives. (±)-1.15 exhibited improved selectivity over other chiral auxiliary controlled dihydroxylations of substituted acrylate esters. In addition, the first total synthesis of the tetracyclic lupin alkaloid (+)-allomatrine (5.01) has been completed in 6% yield over 12 steps. This was followed by a second generation synthesis improving on our previous efforts; increasing the overall yield to 14%. The target molecule was assembled with excellent control of four contiguous stereocentres employing a diastereoselective imino-aldol reaction, ring-closing metathesis and an N-acyliminium cyclisation as key transformations. As part of our studies towards (+)-allomatrine (5.01) we performed the first total synthesis of the unnatural isomeric tricyclic alkaloid; (?)-lamprolobine (6.14) and bicyclic lupin alkaloid (?)-epilupinine (5.62).

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Published date: 30 April 2013
Organisations: University of Southampton, Chemistry

Identifiers

Local EPrints ID: 354592
URI: http://eprints.soton.ac.uk/id/eprint/354592
PURE UUID: 5025695a-decf-4d7c-9293-fdc38cb7a8d7
ORCID for Richard Brown: ORCID iD orcid.org/0000-0003-0156-7087

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Date deposited: 22 Oct 2013 15:07
Last modified: 06 Jun 2018 13:01

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