Scandium(III)‐Catalysed Decarboxylative Addition of β‐Ketoacids to para‐Quinone Methides: Evidence for 1,6‐Addition and Base‐Assisted Decarboxylation Tandem Process

Abstract

A catalytic tandem 1,6-addition/decarboxylation process of β-ketoacids and para-quinone methides under scandium triflate catalysis and subsequent triethylamine treatment has been developed. The 1 H NMR and ESI-HRMS experiments displayed direct evidences for the reaction pathway.[a] Dr.

Trifluoroethanol‐mediated Decarboxylative Addition Reactions of β‐Ketoacids with Diverse Electrophiles

“…Recently, a large number of metal‐ and organocatalyzed conjugate addition reactions of p ‐quinone methides ( p ‐QMs) were reported [12,13] . Chiang and Lu reported the first example of Lewis acid catalyzed decarboxylative addition of β‐ketoacids to p ‐QMs through a tandem 1,6‐addition and decarboxylation pathway [14] . However, metal catalysts and bases are needed to promote the reaction.…”

“…3‐(3,5‐Di‐ tert ‐butyl‐4‐hydroxyphenyl)‐3‐(4‐methoxyphenyl)‐1‐phenylpropan‐1‐one (3 h) [14] . White solid; 81% yield (38.6 mg); 1 H NMR (300 MHz, CDCl 3 ) δ 7.92 (d, J =7.5 Hz, 2H), 7.56–7.53 (m, 1H), 7.47–7.42 (m, 2H), 7.23–7.20 (d, J =8.1 Hz, 2H), 7.04 (s, 2H), 6.83 (d, J =8.1 Hz, 2H), 5.06 (s, 1H), 4.71 (t, J =7.2 Hz, 1H), 3.79 (s, 3H), 4.69–4.66 (m, 2H), 1.40 (s, 18H); 13 C NMR (75 MHz, CDCl 3 ) δ 199.0, 157.9, 152.1, 137.4, 136.7, 135.7, 135.0, 132.9, 128.8, 128.5, 128.1, 124.3, 113.8, 55.2, 45.7, 45.6, 34.3, 30.3.…”

“…3‐(3,5‐Di‐ tert ‐butyl‐4‐hydroxyphenyl)‐1‐phenyl‐3‐(4‐trifluoro‐methyl)pheyl)propan‐1‐one (3 j) [14] . White solid; 73% yield (38.6 mg); 1 H NMR (300 MHz, CDCl 3 ) δ 7.95 (d, J =8.4 Hz, 2H), 7.58–7.55 (m, 3H), 7.47–7.45 (m, 4H), 7.05 (s, 2H), 5.13 (s, 1H), 4.83 (t, J =7.2 Hz, 1H), 3.77–3.73 (m, 2H), 1.41 (s, 18H); 13 C NMR (75 MHz, CDCl 3 ) δ 198.3, 152.5, 148.7, 137.1, 136.0, 133.8, 133.2, 129.5, 129.1, 128.6, 128.1 (q, J =140 Hz), 126.1, 125.4 (q, J =4 Hz), 124.3, 124.0, 123.5, 122.5, 46.1, 45.0, 34.4, 30.2.…”

“…[12,13] Chiang and Lu reported the first example of Lewis acid catalyzed decarboxylative addition of βketoacids to p-QMs through a tandem 1,6-addition and decarboxylation pathway. [14] However, metal catalysts and bases are needed to promote the reaction. We anticipated that fluorinated alcohols can promote this tandem reaction without any base, metal or catalyst.…”

“…[14] 3-(4-Bromophenyl)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-1-pheny lpropan-1-one (3 d). [14] White solid; 93% yield (45.7 mg); 1 Bromophenyl)-3-(3,5-di-tert-butyl-4-hydroxyphenyl)-1phenyl propan-1-one (3 e). [14]…”