Electrophile-Driven Regioselective Synthesis of Functionalized Quinolines

Abstract

Highly substituted 3-iodoquinolines bearing different alkyl and aryl moieties can be synthesized in moderate to excellent yields (up to 99%) by 6-endo-dig iodocyclization of 2-tosylaminophenylprop-1-yn-3-ols with molecular iodine (I(2)) under mild conditions. The cyclization is highly regioselective and the resulting 3-iodoquinolines can be further functionalized by various coupling reactions.

4.07 Electrophilic Cyclization

“…81 Changing the protecting group of nitrogen from dimethyl to Ts, Liang et al reported an efficient and highly regioselective protocol for preparing 3-iodoquinolines (Scheme 75). 82 The resulting 3-iodoquinolines can be further functionalized by using cross-coupling reactions.…”

Synthesis of Iodine‐Substituted Quinolines, Quinolinium Salts, and Isoquinolinium Salts via a Three‐Component Tandem Reaction of Aryl Azides, Propargylic Alcohols, and Iodine

“…Quinolines, quinolinium salts, and isoquinolinium salts are highly important alkaloids with numerous valuable biological activities and other applications, some of which are shown in Figure . For example, 1‐benzyl‐quinolinium chloride can be used to suppress the corrosion process .…”

“…Quinolines are potential therapeutics with antimalarial, anti‐asthmatic, anti‐hypertensive, antibacterial, anti‐inflammatory, and tyrosine kinase inhibitive activities . In particular, halogen‐containing quinolines are of special interest because the halogen atoms could not only play an important role in the bioactivity of the compounds, but are also very useful for further elaboration to other complex molecules . Since the late 1800s, there have been many advances in the synthesis of quinolines, as exemplified by various conventional methods such as Pfitzinger, Friedländer, Skraup, Doebner‐von Miller, Conrad‐Limpach‐Knorr and Combes, as well as a number of recently developed new methods .…”

Oxidation of alcohols to carbonyl compounds with molecular iodine in the presence of potassium tert-butoxide

“…3,4 As an environmentally benign oxidizing agent, molecular iodine has been used in various organic reactions. [5][6][7][8][9] It is known that secondary alcohols are readily converted into ketones, while primary alcohols can be first oxidized into the aldehydes and further into the carboxylic acids or their derivatives. Thus, the oxidation of primary alcohols to the corresponding carbonyl compounds is not so easily controlled as that of secondary alcohols.…”