Preparation and applications of new solid organozinc reagents for the functionalization of aromatics, heteroaromatic and alkykynyl compounds

Tüllmann, Carl Phillip (2020): Preparation and applications of new solid organozinc reagents for the functionalization of aromatics, heteroaromatic and alkykynyl compounds. Dissertation, LMU München: Faculty of Chemistry and Pharmacy

Abstract

This work focused on the development of solid alkynylzinc reagents prepared from the corresponding alkynes through a deprotonation under mild conditions using TMPZnCl·Mg(OPiv)2 as base. After evaporation of the solvent, the resulting solid alkynyl zinc pivalates can be handled in air for several hours without significant decomposition. These zinc reagents show an excellent reactivity in various carbon-carbon bond forming reactions including 1,3-dipolar cycloadditions. Such an alkynylzinc pivalate has been used to prepare a carboxyamidotriazole with potential antineoplastic activity in eight steps in 55% overall yield. In addition, the preparation of mono- and bis-pivaloyloxyzinc acetylides, which display enhanced air and moisture stability was examined. Mono-zinc acetylide pivalate underwent Negishi cross-couplings to form (hetero)aryl alkynes. A subsequent Sonogashira cross-coupling led to the synthesis of asymmetric bis-arylated alkynes without employing silyl protection steps. Furthermore, this zinc reagent underwent a copper-catalyzed azide-alkyne cycloaddition (CuAAC), which selectively led to 1,5-disubstituted 1,2,3-triazoles. In addition, bis pivaloyloxyzinc acetylide reacted in Negishi cross-couplings with aryl halides, yielding symmetrical bis-arylated alkynes. Finally, the preparation of (1H-tetrazol-5-yl)zinc pivalates as storable solids with appreciably high air and moisture stability was developed. They were obtained in high yields from protected 1H-tetrazoles by deprotonation using TMPZnCl·Mg(OPiv)2. Subsequent cross-couplings and copper-catalyzed aminations using hydroxylamino benzoates gave access to functionalized 1H-tetrazoles while tolerating many functional groups

• Item Type: Theses (Dissertation, LMU Munich)
• Keywords: Zinc pivalates, organometalls, zinc, solid, airstable
• Subjects: 500 Natural sciences and mathematics; 500 Natural sciences and mathematics > 540 Chemistry and allied sciences
• Faculties: Faculty of Chemistry and Pharmacy
• Language: English
• Date of oral examination: 27. February 2020
• 1. Referee: Knochel, Paul
• Signature of the printed copy: 0001/UMC 27056