Pivalic Acid

A Study of an 8-Aminoquinoline-Directed C(sp2)–H Arylation Reaction on the Route to Chiral Cyclobutane Keto Acids from Myrtenal

“…A low yield was also observed with 0.2 equiv of pivalic acid (PivOH, entry 3), which constitutes another popular additive for C−H functionalization reactions. 19 To our delight, a better result was obtained with NaOAc as the additive, which was in line with the findings from our previous study on the 8-AQ-directed C(sp 2 )−H arylation of benzofuran derivatives. 15a For example, when the reaction was carried out with 0.2 equiv of NaOAc at 110 °C, product 4a could be obtained in 56% yield with 90% conversion (entry 4).…”

“…Dibenzyl phosphate [(BnO) 2 PO 2 H, 0.2 equiv], ,,, a commonly used additive for C–H functionalizations, was found to have a significant negative effect on this reaction, resulting in an only 12% yield of 4a after 16 h at 110 °C (entry 2). A low yield was also observed with 0.2 equiv of pivalic acid (PivOH, entry 3), which constitutes another popular additive for C–H functionalization reactions . To our delight, a better result was obtained with NaOAc as the additive, which was in line with the findings from our previous study on the 8-AQ-directed C­(sp 2 )–H arylation of benzofuran derivatives .…”

“…1, 147.6, 141.3, 138.3, 138.2, 137.3, 136.1, 134.5, 133.7, 129.2, 128.7, 127.7, 127.3, 121.33, 121.27, 116.2, 44.0, 40.6, 38.3, 38.2, 31.6, 25.8, 21. The reaction was performed according to general method B with 5 mol % Pd(OAc) 2 for 48 h, and the product was isolated after column chromatography (gradient from 0% to 5% EtOAc in pentane) in 42.0 mg (69%) as a white amorphous solid: 147.8, 141.9, 141.7, 138.4, 137.2, 135.9, 134.50, 134.47, 129.8, 127.8, 127.7 (two overlapping C), 127.3, 126.4, 121.4, 121.2, 116.0, 44.0, 40.6, 38.3 (two overlapping C), 31.6, 25.9, 21. The reaction was performed according to general method B with 5 mol % Pd(OAc) 2 , and the product was isolated after column chromatography (gradient from 5% to 10% EtOAc in pentane) in 45.0 mg (67%) as a white amorphous solid: 1 1, 147.7, 141.3, 138.6, 138.3, 137.3, 135.9, 134.5, 131.6, 129.5, 127.7, 127.2, 121.9, 121.34, 121.25, 116.1, 44.0, 40.5, 38.2, 38.1, 31.5, 25.8, 21. The reaction was performed according to general method B with 5 mol % Pd(OAc) 2 , and the product was isolated after column chromatography (gradient from 0% to 10% EtOAc in pentane) in 36.3 mg (49%) as a yellow amorphous solid: 1 7, 147.7, 141.3, 139.2, 138.2, 137.5, 137.4, 136.1, 134.4, 129.8, 127.8, 127.3, 121.4, 121.3, 116.3, 93.5, 44.0, 40.5, 38.2, 38.0, 31.5, 25.8, 21. The reaction was performed according to general method B with 5 mol % Pd(OAc) 2 , and the product was isolated after column chromatography (gradient from 5% to 10% EtOAc in pentane) in 7.5 mg (13%) as a yellow amorphous solid: 1 H NMR (400 MHz, CDCl 3 ) δ 9.63 (s, 1H), 8.72 (dd, 1H, J = 7.56, 1.30 Hz), 8.48 (dd, 1H, J = 4. 19,1.63 Hz),8.03 (dd,1H,J = 8.26,1.63 Hz),1H),7.39 (dd,1H,J = 8.26,1.37 Hz),2H),1H), 7.03−6.97 (m, 2H), 3.05 (t, 1H, J = 5.72 Hz), 2.83 (dd, 1H, J = 18.4, 3.04 Hz), 2.69 (dd, 1H, J = 18.4, 2.61 Hz), 2.63−2.59 (m, 1H), 2.30−2.26 (m, 1H), 1.50 (d, 1H, J = 9.11 Hz), 1.44 (s, 3H), 1.12 (s, 3H); 13 C{ 1 H} NMR (100 MHz, CDCl 3 ) δ 166.6, 159.9 (d, J = 246 Hz), 147. 4,142.9,138.3,136.0,134.5,133.4,130.3,130.2,129.3 (d,J = 8.07 Hz),…”

Stereospecific Palladium-Catalyzed C–H Arylation of Pyroglutamic Acid Derivatives at the C3 Position Enabled by 8-Aminoquinoline as a Directing Group

“…As observed in previous C–H functionalization studies, ,, the addition of dibenzyl phosphate had a positive impact on the performance of this reaction, allowing for arylated product 2a to be obtained in 65% yield (vs 9% without). Pivalic acid (PivOH), a common acidic additive in transition-metal-catalyzed C–H activation reactions, was not found to have the same beneficial effect, and 2a was observed in only 8% yield. The reaction displayed a broad tolerance for solvents, giving moderate to good yields in toluene, 1,4-dioxane, t -BuOAc, MeCN, and cyclopentyl methyl ether (CPME) (entries 5–8).…”