One-Pot Diastereoselective Synthesis of Tetrahydroquinolines from Star Anise Oil in a Choline Chloride/Zinc Chloride Eutectic Mixture

Abstract

In this contribution, a sustainable one-pot diastereoselective synthesis of tetrahydroquinolines through the aza Diels−Alder reaction is reported starting from star anise oil, substituted anilines, and aromatic aldehydes in a choline chloride/zinc chloride eutectic mixture as new reaction media. Star anise extracts and essential oils obtained by Soxhlet, ultrasound-assisted extraction, steam distillation, and hydrodistillation were analyzed by gas chromatography− mass spectrometry finding the highest content of trans-anethol from hydrodistillation; in addition, the eutectic composition and temperature for the choline chloride/zinc chloride mixture were revisited. All the compounds were obtained in 28−98% yield with diastereoselectivity toward the cis-(2e,4e) product. Furthermore, the deep eutectic solvent was reused in three cycles without observing a detrimental catalytic activity, and green metric analysis showed a favorable environmental impact of this synthetic method.

The Povarov Reaction: A Versatile Method to Synthesize Tetrahydroquinolines, Quinolines and Julolidines

“…This strategy was employed for the microscale synthesis of DNA-tagged THQs at room temperature with yields over 90%. 96 Peñaranda Gómez et al 94 reported the diastereoselective synthesis of THQs 23 via a one-pot multicomponent Povarov reaction of aromatic amines 2, aldehydes 19, and star anise oil [which is composed mostly of trans-anethole (22)] in a mixture of choline chloride (ChCl) and zinc chloride as a DES (Scheme 5). The method developed is simple, efficient, and eco-friendly, with short reaction times and high diastereoselectivity, affording THQs 23 in yields of 28-98%.…”

“…Fluorinated alcohols, such as hexafluoroisopropanol (HFIP) 71 and trifluoroethanol (TFE) 50,93 can be employed to dissolve reagents that are insoluble in the most common solvents, 71 or can even act as the catalyst itself, thereby removing the requirement for the addition of acids. 93 Greener approaches towards the use of solvents have also been explored by using biodegradable carbonates, 61 water, 55,57,86 a deep eutectic solvent (DES), 94 or simply no solvent at all. 56,84,95 With respect to the substrates, macromolecules pose a particular challenge, especially nucleic acids, which are sensitive to acidic media, making the typical Lewis or Bronsted catalysts unsuitable.…”

“…Scheme 5 Diastereoselective synthesis of THQs by Peñaranda Gómez et al 94 An uncommon and softer type of catalysis for the THQforming Povarov reaction is the use of halogen bonding, in which a * orbital of an electron-deficient halogen atom interacts with a nucleophilic electron pair such as  systems or non-bonding pairs. For instance, the use of 2-iodoimidazolium triflate 26 selectively led to the corresponding THQ Most methodologies rely on electron-rich dienophiles, like vinyl ethers, furnishing predominantly cis THQ diastereoisomers.…”

“…Subsequent to the work of Grieco and Bahsas, in 1995, Mellor and Merriman reported the use of the Povarov reaction for the synthesis of julolidines. 25 Different julolidines were obtained by reacting 4-methylaniline (94) [or THQ (89)], formaldehyde (87), and styrene (65) [or 3,4-dihydro-…”

Efficient synthesis of new 6-arylphenanthridines based on microwave-assisted Suzuki–Miyaura cross-coupling and Pictet–Spengler dehydrogenative cyclization in a zinc chloride/[Bmim]BF4 mixture

“…Based on our previous study for the design and preparation of nitrogen-containing heterocycles as potential bioactive agents under green reaction conditions, 28,29 we were particularly interested in green protocols for the synthesis of important substituted phenanthridines under simultaneous microwave and ionic liquid (IL) or deep eutectic solvent (DES) assistance. The latter implements are well-studied promising tactics looking for a greener and more efficient process of synthesis.…”