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Synthesis of Isoquinolin‐4‐ols by Palladium‐Catalysed Intramolecular Nucleophilic Addition of Aryl Iodides to Aldehydes
Author(s) -
Solé Daniel,
Mariani Francesco,
Fernández Israel
Publication year - 2014
Publication title -
advanced synthesis and catalysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.541
H-Index - 155
eISSN - 1615-4169
pISSN - 1615-4150
DOI - 10.1002/adsc.201400408
Subject(s) - chemistry , nucleophile , intramolecular force , aryl , palladium , triethylamine , nucleophilic addition , medicinal chemistry , base (topology) , organic chemistry , catalysis , alkyl , mathematical analysis , mathematics
A palladium‐catalysed intramolecular nucleophilic addition of aryl iodides to aldehydes leading to tetrahydroisoquinolin‐4‐ols is reported. A variety of products were isolated in good to excellent yields. The joint experimental‐computational study shows that although two competitive reaction pathways can be promoted by Pd(0) starting from α‐(2‐iodobenzylamino)‐aldehydes, the selectivity of the process can be controlled by the proper selection of the base. While the nucleophilic addition of the aryl‐Pd(II) intermediate to the carbonyl group is selectively promoted by using the base triethylamine (Et 3 N), the CH bond activation at the formyl group competes with the nucleophilic addition only when the base is replaced by cesium carbonate (Cs 2 CO 3 ).