Sulfonic Acid Functionalized Silica: A Mild, Reusable and Efficient Heterogeneous Catalyst for the Highly Diastereoselective Synthesis of cis-Isoquinolonic Acids

Abstract

Sulfonic acid functionalized silica (SAFS) is found to be a recyclable heterogeneous catalyst for the rapid and efficient synthesis of various cis-isoquinolonic acids from the three-component condensation reaction of homophthalic anhydride, an amine, and an aldehyde. This reaction was highly diastereoselective and only one diastereomer was obtained in all cases.

Homogeneous and heterogeneous catalysts for multicomponent reactions

“…Recently, Karimi et al 366 have reported the use of sulfonic acid functionalized silica (SAFS) as a recyclable heterogeneous catalyst for the synthesis of isoquinolonic acids by a three component condensation of homophthalic anhydride, aldehydes and amines. When the reaction was carried out at room temperature in the presence of acetonitrile, good yields of the isoquinolonic acid derivatives were obtained (78-98%) in 1-5 h. The reaction was highly diastereoselective and only the cis diasteromer was obtained in all cases.…”

Mechanistic Investigation of Castagnoli–Cushman Multicomponent Reactions Leading to a Three-Component Synthesis of Dihydroisoquinolones

“…The CCR also forms the basis of a three-component reaction (3CR) of homophthalic anhydride, amines, and aldehydes with Lewis acid catalysts and additives. − In one case, a diacid is used as an anhydride precursor . Similar zwitterionic intermediates were proposed for the 3CR of homophthalic anhydride with amines and aldehydes, wherein the amine attacks homophthalic anhydride to form amide-acid 11 , followed by condensation with aldehyde 9 and successive Mannich addition (Figure A) .…”

Trifluoroethanol Promoted Castagnoli–Cushman Cycloadditions of Imines with Homophthalic Anhydride

“…Recently, 3,4trans-isoquinolonic acids have been prepared without catalyst by heating homophthalic anhydride IVa with different amines and aldehydes in the presence of Na 2 SO 4 in refluxing toluene [20]. 3,4-cis-isoquinolonic acids have been prepared in the presence of ionic liquids [21], trimethyl orthoformate [22], Yb(OTf) 3 [23], silica sulfuric acid [24], sulfonic acid functionalized silica [25], KAl(SO 4 ) 2 •12H 2 O [26], or L-proline [27]. The formations of cis-isoquinolonic acids under the conditions described above took several hours at room temperature or reflux in different solvents (Scheme 1a).…”