Enantioselektivní katalyzátory odvozené od amidů a thioamidů (3\kur{S})-1,2,3,4-tetrahydroisochinolin-3-karboxylové kyseliny

Ing. Ladislav Androvič

Master's thesis

Enantioselective catalysts derived from amides and thioamides of (3\kur{S})-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid

Abstract:

Souhrn Bylo připraveno a charakterizováno osm nových opticky čistých N-substituovaných (S)-1,2,3,4-tetrahydroisochinolin-3-karboxamidů a thioamidů: (3S)-1,2,3,4-tetrahydro-isochinolin-3-karboxamid (3S)-N-(pyridin-2-yl)-1,2,3,4-tetrahydroisochinolin-3-karboxamid, (3S)-N-benzyl-1,2,3,4-tetrahydroisochinolin-3-karbox-amid, (3S)-N-[(1S)-1-fenylethyl]-1,2,3,4-tetrahydro-isochinolin-3-karboxamid, (3S)-N-[(1R)-1-fenylethyl]-1,2,3,4-tetrahydro-isochinolin-3-karboxamid, (3S)-N-[(4-methylfenyl)sulfonyl]-1,2,3,4-tetrahydro-isochinolin-3-karboxamid, (3S)-N-[(1S)-1-fenylethyl]-1,2,3,4-tetrahydroiso-chinolin-3-karbothioamid a (3S)-N-[(1R)-1-fenylethyl]-1,2,3,4-tetrahydro-isochinolin-3-karbothioamid. Tyto amidy a thioamidy byly testovány jako organokatalyzátory aldolizační reakce acetonu s 4-nitrobenzaldehydem (20 mol% katalyzátoru; 25 °C, - 10 °C). Thioamidy poskytují vyšší enantioselektivitu vzniku (4R) nebo (4S)-4-hydroxy-4-(4-nitrofenyl)butan-2-onu ve srovnání s analogickými amidy. (3S)-N-[(1R)-1-Fenylethyl]-1,2,3,4-tetrahydroisochinolin-3-karbothioamid poskytuje v dané sérii nejlepší enantioselektivní výtěžek (17%, 77% ee), katalyzuje však mnohem pomaleji než analogický (S)-prolinový derivát (62 % ; 84% ee ).

Abstract:

Eight new optically pure N-substituted (S)-1,2,3,4-tetrahydroisoquinoline-3-carboxamides and thioamides were prepared and characterised: (3S)-1,2,3,4-tetrahydroisoquinoline-3-carboxamide (3S)-N-(pyridin-2-yl)-1,2,3,4-tetrahydroisoquinoline-3-carboamide, (3S)-N-benzyl-1,2,3,4-tetrahydroisoquinoline-3-carboxamide, (3S)-N-[(1S)-1-phenylethyl]-1,2,3,4-tetrahydro-isoquinoline-3-carboxamide, (3S)-N-[(1R)-1-phenylethyl]-1,2,3,4-tetrahydro-isoquinoline-3-carboxamide, (3S)-N-[(4-methylphenyl)sulfonyl]-1,2,3,4-tetrahydro-isoquinoline-3-carboxamide, (3S)-N-[(1S)-1-phenylethyl]-1,2,3,4-tetrahydroisoquinoline-3-carbothioamide and (3S)-N-[(1R)-1-phenylethyl]-1,2,3,4-tetrahydroisoquinoline-3-carbothioamide. These amides and thioamides were tested as organocatalysts for aldolization of acetone with 4-nitrobenzaldehyde (20mol% catalyst, 25°C, -10°C). Thioamides provide higher enantioselectivity of formation of (4R) or (4S)-4-hydroxy-4-(4-nitrophenyl)butan-2-one compared with analogic amides. (3S)-N-[(1R)-1-Phenylethyl]-1,2,3,4-tetrahydroisoquinoline-3-carbothioamide provides in the reaction sequence the best enantioselective excess (17%, 77% ee), but catalyses more slowly than analogic (S)-proline derivative (62%, 84%ee)

Keywords

aldolizace, enantioselektivita, organokatalýza, tetrahydroisochinolin-3-karboxamidy

Language used: Czech

Date on which the thesis was submitted / produced: 21. 5. 2012

Thesis defence

• Date of defence: 4. 6. 2012
• Supervisor: prof. Ing. Miloš Sedlák, DrSc.

University of Pardubice

Faculty of Chemical Technology

Master programme / field:
Chemistry / Organic Chemistry