Catalytic enantioselective synthesis of 1,4-dihydropyridines via the addition of C(1)-ammonium enolates to pyridinium salts.

Autor:	McLaughlin C; EaStCHEM, School of Chemistry, University of St Andrews St Andrews Fife KY16 9ST UK ads10@st-andrews.ac.uk., Bitai J; EaStCHEM, School of Chemistry, University of St Andrews St Andrews Fife KY16 9ST UK ads10@st-andrews.ac.uk., Barber LJ; EaStCHEM, School of Chemistry, University of St Andrews St Andrews Fife KY16 9ST UK ads10@st-andrews.ac.uk., Slawin AMZ; EaStCHEM, School of Chemistry, University of St Andrews St Andrews Fife KY16 9ST UK ads10@st-andrews.ac.uk., Smith AD; EaStCHEM, School of Chemistry, University of St Andrews St Andrews Fife KY16 9ST UK ads10@st-andrews.ac.uk.
Jazyk:	angličtina
Zdroj:	Chemical science [Chem Sci] 2021 Aug 06; Vol. 12 (36), pp. 12001-12011. Date of Electronic Publication: 2021 Aug 06 (Print Publication: 2021).
DOI:	10.1039/d1sc03860e
Abstrakt:	The regio- and stereoselective addition of C(1)-ammonium enolates - generated in situ from aryl esters and the isothiourea catalyst ( R )-BTM - to pyridinium salts bearing an electron withdrawing substituent in the 3-position allows the synthesis of a range of enantioenriched 1,4-dihydropyridines. This represents the first organocatalytic approach to pyridine dearomatisation using pronucleophiles at the carboxylic acid oxidation level. Optimisation studies revealed a significant solvent dependency upon product enantioselectivity, with only toluene providing significant asymmetric induction. Using DABCO as a base also proved beneficial for product enantioselectivity, while investigations into the nature of the counterion showed that co-ordinating bromide or chloride substrates led to higher product er than the corresponding tetrafluoroborate or hexafluorophosphate. The scope and limitations of this process are developed, with enantioselective addition to 3-cyano- or 3-sulfonylpyridinium salts giving the corresponding 1,4-dihydropyridines (15 examples, up to 95 : 5 dr and 98 : 2 er). Competing Interests: There are no conflicts to declare. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
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