An expeditious and efficient synthesis of symmetrical tris(indolyl)methanes under catalyst-free conditions in fluorinated alcohols

HFIP in Organic Synthesis

“…Similarly, the condensation of indole derivatives with orthoesters in HFIP at rt furnished symmetrical tris­(indolyl)­methanes in high yields (Scheme ). The weak Brønsted acidity of HFIP activates the orthoester toward the reaction.…”

Lewis acid free synthesis of 3,4-dihydro-1H-indazolo[1,2-b]phthalazine-1,6,11(2H,13H)-triones promoted by 1,1,1,3,3,3-hexafluoro-2-propanol

“…Reactions in 1,1,1,3,3,3-hexauoro-2-propanol (HFIP) have a facile isolation of the product and can be easily recovered by distillation. [25][26][27] HFIP has been used in organic synthesis because these uorinated alcohols are available on a commercial scale. They can be well dispersed in the reaction mixtures in solvolysis reaction, where the generated cationic intermediates can be trapped by nucleophiles.…”

“…In this process, HFIP with a strong H-bond donor (a ¼ 1.96, pK a ¼ 9.3), high ionizing power (Y OTs ¼ 3.79), and polarity (P s ¼ 11.08) could activate the C]O groups and play a signicant role in increasing the electrophilic character. [25][26][27] Therefore, The formation of products 4a-p can be rationalized by initial formation of heterodiene by standard Knoevenagel condensation of cyclic 1,3-diketones and aromatic aldehydes in the presence of a catalytic amount. Subsequent Michael-type addition of phthalhydrazide to the heterodienes followed by cyclization and dehydration afford the corresponding products 4a-p (Scheme 2).…”

Applications of alkyl orthoesters as valuable substrates in organic transformations, focusing on reaction media

“…349 In 2012, Khaksar and co-workers prepared symmetrical tris(indolyl)methanes 349,350 via a catalyst-free reaction of indoles with orthoesters in the presence of hexauoro-2-propanol (HFIP) at room temperature within 15-60 min in excellent yields (88-98%). 350 6-Monosubstituted and 6,12-disubstituted 5,11-dihydroindolo[3,2-b]carbazoles (381) were synthesized in 20-50% yields via the one-pot three-stage condensation reaction of indole (89) and aldehydes (378) using a catalytic amount of iodine; which underwent an acid-mediated intramolecular ringclosure reaction by orthoesters (5,6,7,380) in methanol at room temperature for 14 h (Scheme 108). 351…”

“…In 2012, Khaksar and co-workers prepared symmetrical tris(indolyl)methanes 349,350 via a catalyst-free reaction of indoles with orthoesters in the presence of hexafluoro-2-propanol (HFIP) at room temperature within 15–60 min in excellent yields (88–98%). 350 …”