Diversity‐Oriented Synthesis of Intensively Blue Emissive 3‐Hydroxyisoquinolines by Sequential Ugi Four‐Component Reaction/Reductive Heck Cyclization

Abstract

A convergent approach to highly functionalized 3-hydroxyisoquinolines is reported. The key steps are an Ugi multicomponent reaction and a subsequent intramolecular reductive Heck reaction; these can also be performed as a one-pot procedure. The structures display very interesting properties as blue-fluorescence emitters. Photophysical studies on the absorption and static fluorescence indicate that the substitution pattern on the pyridyl part influences the optical properties only to a minor extent, unless the amide substituent becomes sterically demanding and leads to significant nonradiative deactivation. The donor substitution on the benzo core considerably enhances the fluorescence quantum yields and trimethoxy substitution causes a pronounced redshift of the emission bands. Protonation of the isoquinolyl nitrogen atom causes efficient static quenching of the fluorescence.

Highly Convergent Synthesis of Intensively Blue Emissive Furo[2,3‐c]isoquinolines by a Palladium‐Catalyzed Cyclization Cascade of Unsaturated Ugi Products

“…[16] This was the consequence of an unexpected result:w ei nitiallyp lanned to prepare pyranoisoquinolines 3 from Ugi adducts 1,t hrough ad omino Heck cyclization-Sonogashira coupling-cyclization process, introducingaseconda lkyne fragment after the multicomponent reaction ( Scheme1). Surprisingly,t his protocol, previously successfully applied for the synthesis of other heterocycles, [14] did not work, but insteada fforded scaffold 2,w ith no trace of 3.T herefore, because the additional alkyne was not incorporated,i tw as completely omitted, as well as cuprous salts, during the optimization of the synthetic procedure to-wards 2.H owever,i no ne instance, employing Ugi adduct 1 (R 3 = Ph), we isolated as ignificant amount (19 %) of compound 4 as ab yproduct, in whicha na dditional PhÀCC carbon fragment was included.…”

“…[16] Moreover,a ne xcess of NH 3 wasn ecessary and, in view of ap ossible one-pot synthesis of 4,w ew ere aware of its incompatibilityw ith palladium chemistry.F or these reasons, we turned our attention to the cyclization of Ugi products in which ap rimary amine with ac leavable group was used instead of ammonia (Scheme 2). [16] Even disregarding the atom-economyp rinciple, the typically highero verall yield compensates for this choice. Therefore, we Scheme1.Initial attempt to preparepyranoisoquinolines 3 from Ugi adducts 1,t hrough ad omino Heck cyclization-Sonogashira coupling-cyclization process.…”

“…Therefore, we Scheme1.Initial attempt to preparepyranoisoquinolines 3 from Ugi adducts 1,t hrough ad omino Heck cyclization-Sonogashira coupling-cyclization process. submitted the previously prepared compound 5a [16] to the conditions shown in Ta ble 1, entry 8.…”

“…, 22,2020Eur.J. -2031 www.chemeurj.org furo [2,3-c]isoquinolines 4,v arying the structure of three of the four componentso ft he Ugi reaction;t he structure of the amine was fixed for our purposes.W eu sed either commercially available substrates or custom-made startingm aterials prepared according to known procedures [16] or new syntheses described in the Supporting Information.…”

“…[10b, 15] Recently,w ee xpanded the insertion scenarioi nt he sense of ar eductive post-Ugi Heck transformation into Ugi four-component reaction( 4CR) products, giving rise to multiply substituted, blue-emissive 3-hydroxyisoquinolines. [16] Herein, we report the palladium-catalyzed insertion-alkynylation-cycloisomerization of similar Ugi-4CRs ubstrates to give furo [2,3-c]isoquinolinese fficiently in ad ominofashion. The conspicuous intense blue luminescence is studied by absorptiona nd emission spectroscopy,a sw ell as by computationale lucidation of the electronic structureo ft he furo [2,3-c]isoquinolines.…”