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Published on: April 9, 2021
Sequential Michael Addition/Electrophilic Alkynylation: Synthesis of α-Alkynyl-β-Substituted Ketones and Chromanones
Bruno V M Teodoro1, Luiz F Silva1
1Departamento de Química Fundamental, Instituto de Química , Universidade de São Paulo , São Paulo 05508-000 , Brazil.
Abstract:
We describe the synthesis of α-alkynyl-β-substituted cyclic ketones and analogue chromanones via one-pot Michael addition/hypervalent iodine-based α-alkynylation. Cu(I)-catalyzed Michael addition using either alkyl-aluminum or Grignard reagents, followed by diastereoselective electrophilic alkynylation of the resulting enolate by 1-ethynyl-1λ3,2-benziodoxol-3(1H)-one (EBX) resulted in the α-alkynyl-β-substituted cyclic ketones or chromanones within 34-89% yield (16 examples). The reaction was successfully upscaled to the 5 mmol scale, and further functionalization of a model alkynylated ketone was demonstrated.
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Halogenation is another class of electrophilic addition reactions where a halogen molecule gets added across a π bond. In alkynes, the presence of two π bonds allows for the addition of two equivalents of halogens (bromine or chlorine). The addition of the first halogen molecule forms a trans-dihaloalkene as the major product and the cis isomer as the minor product. Subsequent addition of the second equivalent yields the tetrahalide.
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