Evaluating aryl esters as bench-stable C(1)-ammonium enolate precursors in catalytic, enantioselective Michael addition–lactonisations

Claire Young, James Taylor, Andrew Smith

Research output: Contribution to journalArticle

Abstract

An evaluation of a range of aryl, alkyl and vinyl esters as prospective C(1)-ammonium enolate precursors in enantioselective Michael addition–lactonisation processes with (E)-trifluoromethylenones using isothiourea catalysis is reported. Electron deficient aryl esters are required for reactivity, with 2,4,6-trichlorophenyl esters providing optimal product yields. Catalyst screening showed that tetramisole was the most effective isothiourea catalyst, giving the desired dihydropyranone product in excellent yield and stereoselectivity (up to 90 : 10 dr and 98 : 2 er). The scope and limitations of this process have been evaluated, with a range of diester products being generated after ring-opening with MeOH to give stereodefined dihydropyranones with excellent stereocontrol (10 examples, typically ∼90 : 10 dr and >95 : 5 er).
LanguageEnglish
JournalOrganic and Biomolecular Chemistry
Early online date11 Apr 2019
DOIs
StatusE-pub ahead of print - 11 Apr 2019

Cite this

@article{86971b4e68d746b49d3b23d63ba7430e,
title = "Evaluating aryl esters as bench-stable C(1)-ammonium enolate precursors in catalytic, enantioselective Michael addition–lactonisations",
abstract = "An evaluation of a range of aryl, alkyl and vinyl esters as prospective C(1)-ammonium enolate precursors in enantioselective Michael addition–lactonisation processes with (E)-trifluoromethylenones using isothiourea catalysis is reported. Electron deficient aryl esters are required for reactivity, with 2,4,6-trichlorophenyl esters providing optimal product yields. Catalyst screening showed that tetramisole was the most effective isothiourea catalyst, giving the desired dihydropyranone product in excellent yield and stereoselectivity (up to 90 : 10 dr and 98 : 2 er). The scope and limitations of this process have been evaluated, with a range of diester products being generated after ring-opening with MeOH to give stereodefined dihydropyranones with excellent stereocontrol (10 examples, typically ∼90 : 10 dr and >95 : 5 er).",
author = "Claire Young and James Taylor and Andrew Smith",
year = "2019",
month = "4",
day = "11",
doi = "10.1039/C9OB00703B",
language = "English",
journal = "Organic and Biomolecular Chemistry",
issn = "1477-0520",
publisher = "Royal Society of Chemistry",

}

TY - JOUR

T1 - Evaluating aryl esters as bench-stable C(1)-ammonium enolate precursors in catalytic, enantioselective Michael addition–lactonisations

AU - Young, Claire

AU - Taylor, James

AU - Smith, Andrew

PY - 2019/4/11

Y1 - 2019/4/11

N2 - An evaluation of a range of aryl, alkyl and vinyl esters as prospective C(1)-ammonium enolate precursors in enantioselective Michael addition–lactonisation processes with (E)-trifluoromethylenones using isothiourea catalysis is reported. Electron deficient aryl esters are required for reactivity, with 2,4,6-trichlorophenyl esters providing optimal product yields. Catalyst screening showed that tetramisole was the most effective isothiourea catalyst, giving the desired dihydropyranone product in excellent yield and stereoselectivity (up to 90 : 10 dr and 98 : 2 er). The scope and limitations of this process have been evaluated, with a range of diester products being generated after ring-opening with MeOH to give stereodefined dihydropyranones with excellent stereocontrol (10 examples, typically ∼90 : 10 dr and >95 : 5 er).

AB - An evaluation of a range of aryl, alkyl and vinyl esters as prospective C(1)-ammonium enolate precursors in enantioselective Michael addition–lactonisation processes with (E)-trifluoromethylenones using isothiourea catalysis is reported. Electron deficient aryl esters are required for reactivity, with 2,4,6-trichlorophenyl esters providing optimal product yields. Catalyst screening showed that tetramisole was the most effective isothiourea catalyst, giving the desired dihydropyranone product in excellent yield and stereoselectivity (up to 90 : 10 dr and 98 : 2 er). The scope and limitations of this process have been evaluated, with a range of diester products being generated after ring-opening with MeOH to give stereodefined dihydropyranones with excellent stereocontrol (10 examples, typically ∼90 : 10 dr and >95 : 5 er).

U2 - 10.1039/C9OB00703B

DO - 10.1039/C9OB00703B

M3 - Article

JO - Organic and Biomolecular Chemistry

T2 - Organic and Biomolecular Chemistry

JF - Organic and Biomolecular Chemistry

SN - 1477-0520

ER -