The Oxa‐Pictet–Spengler Reaction: A Highlight on the Different Efficiency between Isochroman and Phthalan or Homoisochroman Derivative Syntheses

Abstract

Recently we reported that 6-hydroxy-and 6,7-dihydroxyisochromans can be obtained under very mild conditions and with very good yield by a one-pot synthesis based on a modified oxa-Pictet-Spengler reaction. In this paper, we demonstrate that the above reaction is also useful for the synthesis of hydroxyphthalans, and we discuss the effects of the sub-

Synthesis of Oxacycles Employing the Oxa‐Pictet–Spengler Reaction: Recent Developments and New Prospects

“…No similar ring cleavage process has been reported among the analogous six-membered oxacyles; however, since phenylacetones are prone to self-condense under acid conditions, [77] the occurrence of this transformation cannot be fully discarded. Guiso and co-workers [78] recently also reported the synthesis of 1,3,4,5-tetrahydro-benzo [c]oxepines (homoisochromans) through the oxa-Pictet-Spengler reaction of 3-(3,4-dihydroxyphenyl)-1-propanol and 3-(3-hydroxyphenyl)-1-propanol with various aromatic aldehydes in MeOH under TsOH promotion at 37°C for one week. Yields ranged from 20 to 45 %, being higher with the more activated alcohol.…”

“…[75,90] Phthalans are very important heterocycles with interesting applications in diverse fields. [91] Guiso and coworkers [78] demonstrated that the oxa-Pictet-Spengler reaction is also useful for the synthesis of polysubstituted phthalans; these authors also investigated and discussed the effects of the substituents on the aromatic rings of the alcoholic moiety and on the aldehyde on the course of the reaction. 3-Hydroxybenzyl alcohol, as well as the symmetrically substituted 3,5-dihydroxybenzyl alcohol, and 3,5-dimethoxybenzyl alcohol were employed, in conjunction with aromatic and aliphatic aldehydes, and the reaction was carried in MeOH, employing catalytic amounts of TsOH.…”

Cyclization Reactions for the Synthesis of Phthalans and Isoindolines­

“…The first work in 2008 was reported by Marra and coworkers, which described the preparation of hydroxyphthalans 5 by acid-catalyzed condensation of benzyl alcohols 3 with 3,4,5-trisubstituted benzaldehydes 4 in methanol as solvent (Scheme 3). 15 In 2011, Khosropour and co-workers developed a new protocol that consisted of the use of nanosilica sulfuric acid (NSSA), obtained by adding chlorosulfonic acid to nanosilica (SiO 2 ) at room temperature, as reusable heterogeneous Several examples of the thermal IMDA reaction of these systems have been reported. Shealy and co-workers reported the reaction of retinyl prop-2-ynyl and but-2-ynyl ethers in refluxing ethanol and toluene, respectively; the resulting cycloadducts were treated at room temperature with 2,3dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) in dry benzene to yield the corresponding phthalans.…”

One-Pot Synthesis of Spiro-isobenzofuran Compounds via the Sequential Condensation/Oxidation Reaction of Ninhydrin with 4-Amino-1,2-naphthoquinones/2-Amino-1,4-naphthoquinones under Mild Conditions

“…On the other hand, the isobenzofuran scaffolds, particularly phthalides (isobenzofuran-1(3 H )-ones), exist in many natural and synthetic biologically active materials and their derivatives display various biologically active properties as well as other uses including as colorants and perfumes. 6 In addition, many of their derivatives have been used as synthons for the synthesis of complex molecules. 7 Due to the chemical importance and biological applications of isobenzofurans, their synthesis has attracted the interest of various research groups and quite a lot of methods have been developed.…”