Minisci‐Type Alkylation of N‐Heteroarenes by N‐(Acyloxy)phthalimide Esters Mediated by a Hantzsch Ester And Blue LED Light

Abstract

A synthetic method that enables the Hantzsch ester‐mediated Minisci‐type C2‐alkylation of quinolines, isoquinolines and pyridines by N‐(acyloxy)phthalimide esters (NHPI) under blue LED (light emitting diode) light (456 nm) is described. Achieved under mild reaction conditions at room temperature, the metal‐free synthetic protocol was shown to be applicable to primary, secondary and tertiary NHPIs to give the alkylated N‐heterocyclic products in yields of 21–99%. On introducing a chiral phosphoric acid, an asymmetric version of the reaction was also realised and provided product enantiomeric excess (ee) values of 53–99%. The reaction mechanism was delineated to involve excitation of an electron‐donor acceptor (EDA) complex, formed from weak electrostatic interactions between the Hantzsch ester and NHPI, which generates the posited radical species of the redox active ester that undergoes addition to the N‐heterocycle.

Photo‐triggered Intramolecular Radical Tandem Regioselective Alkylation/Cyclization of 1,6‐Dienes with Redox‐Active Esters Enabled by an EDA Complex

“…Next, an evaluation of different organoamines as electron donor including pentamethyl diethylenetriamine (PMDETA), N,N-diisopropylet-hylamine (DIPEA), N,N,N',N'-tetramethylethylenediamine (TMEDA), 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU) and triethylenedi-amine (DABCO) showed that the addition of organoamines cannot improve the yield (Table 1, entries 6-10). Encouraged by the preliminary results, the effect on light source on this model reaction was further investigated (Table 1, entries [11][12]. The result indicated that 380-385 nm illumination exhibited a better effect on model reaction.…”

A practical and sustainable two-component Minisci alkylation via photo-induced EDA-complex activation

“…Both redox-active ester 2a and pyridinium salt 2a 0 were probed in optimization studies, owing to their pervasive utilization as effective electron-acceptor partners in EDA chemistry (Table 1). [31][32][33][34][35][36][37][38] Gratifyingly, treatment of isoquinoline 1a (1 equiv.) with redox-active ester 2a (1.5 equiv.)…”

“…The adduct formed subsequently undergoes deprotonation followed by oxidation via another molecule of redox-active ester 2 (ref. 24 and 33) to furnish the desired product 3 along with another alkyl radical species 7 to participate in the radical chain propagation step. Given that the experimentally determined quantum yield is high, but <1, ( Φ = 0.62, see ESI†), it seems likely that the two pathways coexist, with the radical ion pair recombination mechanism prevailing.…”

“…32 During the course of this investigation, Chan et al reported that the commercially available Hantzsch ester, an established organo-reductant in EDA chemistry, could be used in the presence of trifluoroacetic acid to perform Minisci alkylations on heterocycles by generating alkyl radicals under photocatalyst-free conditions. 33…”

Visible-light-driven site-selective alkylation of the benzo core of coumarins

“…Regioselective functionalization of the C(sp 2 )–H bond of aromatic molecules has posed unparalleled challenges 1 as scaffolds with C–H bonds of various degrees of chemical reactivity led to unwanted mixtures of regioisomers. 2 To overcome this, usually, exploitation of the subtle steric and electronic differences at the reactive sites by addition of functional groups 3 along with simple use of chelating agents 4 is utilized.…”