Chalcogen-alkynes: Synthesis and application in multicomponent reactions to achieve quinolines, propargyl amines and vinyl β-borylated esters

Author(s)

Isadora Maria de Oliveira

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ)
• Defense date: 2020-04-28

Examining board members

Helio Alexandre Stefani; Erick Leite Bastos; Antonio Carlos Bender Burtoloso; Marcio Weber Paixão

• Advisor: Helio Alexandre Stefani

Abstract

Chalcogen-alkynes had shown a high regioselectivity and proven that they are versatile intermediaries. Methodologies were developed to obtain internal and terminal chalcogen alkynes containing sulfur, selenium and tellurium, as well as aryl and alkyl groups. These compounds were used in the synthesis of 4-chalcogen-quinolines, chalcogen-propargyl amines and vinyl β-borylated chalcogen esters. Chalcogen-quinolines derivatives both 2,4 disubstituted (28 examples, 15-69%) and 2,3,4-trisubstituted (13 examples, 20-62%) good yields were obtained, as well as their functionalizations have been successfully described. The 2,4-disubstituted chalcogen-quinoline libraries were submitted for antifungal and anticancer tests, and the observed results have demonstrated a promising potential. The A3-coupling for obtaining chalcogen-propargylamine (20 examples, 15-85%) has been described in use of internal chalcogen-alkyne, the desilylation reaction occurs in situ using a biocatalytic system combining CuCl and succinic acid. The chalcogen-propargylamine were functionalized employing different methodologies, such as the hydrohalogenation reaction (3 examples, 70-93%) with the subsequent coupling of Sonogashira to reach chalcogen-enynes (6 examples, 46-66%), and also in cyclization reactions with FeCl3 and diaryl dichalcogenides, for the formation of 4H-chalcogenchromenes (15 examples, 22-94%). Finally, hydroboration reactions of the internal chalcogen-alkyne were described to achieve regioselective vinyl β-borylated chalcogen esters (18 examples, 20-85%) under copper catalysis and with carbene ligands with imidazole nucleus. These ligands had allowed the obtention of products with only one isomer, thus showing their high regioselectivity. Then, the β-borylated chalcogen vinyl esters were oxidized under mild conditions to form α-chalcogen-ketones (16 examples, 43-93%), which are versatile synthetic intermediates. (AU)

• FAPESP's process: 16/04289-3 - Synthesis of calcogeno amino acids derivatives and 4-calcogeno quinolines via multicomponent reactions
• Grantee: Isadora Maria de Oliveira
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)