Formation of Methylene Linkage for N-Heterocycles: Sequential C–H and C–O Bond Functionalization of Methanol with Cosolvent Water

Abstract

An iron-catalyzed methylene forming strategy is disclosed through sequential C–H and C–O bond functionalization of methanol with cosolvent water. This protocol provides an easy and novel access to methylene-tethered imidazo­[1,2-a]­pyridine and 2-aminopyridine analogues in a sustainable manner and represents a complementary approach to traditional methylene forming strategies.

Recent Advances in Cross‐Dehydrogenative Couplings (CDC) of C−H Bond in Aqueous Media

“…Rao et al [34] . proposed an iron‐catalyzed methylene‐forming strategy from methanol by using the co‐solvent water and successfully realized the cross‐dehydrogenative coupling of C−H bond of methanol, 2‐arylimidazo[1,2‐α]pyridine and 2‐aminopyridine [Eq.…”

“…Rao et al [34] proposed an iron-catalyzed methyleneforming strategy from methanol by using the cosolvent water and successfully realized the cross- Wu et al [35] reported a highly efficient and environmentally friendly visible light-mediated CDC reaction of N-phenyl-1,2,3,4-tetrahydroisoquinolines and indoles by using a catalytic amount of CoCl 2 with dmgH (dimethylglyoxime) as ligand to form an in situ photosensitizer [Eq. (20)].…”

“…Joshi and co-workers [49] developed a water-mediated green strategy for C sp2 À C sp2 dehydrogenative coupling between phenylpyrazole and alkene using Rh(III) catalyst under aerobic and very mild reaction conditions[Eq. (34)]. This method achieved selectivity of mono and di-vinylation formation by temperature and was very effective for the synthesis of unsymmetrical di-vinylated CDC products.…”

Recent Advances in Radical C−H Bond Functionalization of Imidazoheterocycles

“…Homolytic fission of TBHP produced t BuO * Later, Rao and co-workers reported FeCp 2 -catalyzed aminomethylation of imidazopyridines with 2aminopyridines using MeOH as carbon synthon and co-solvent and TBHP as oxidant under inert atmosphere (Scheme 28). [47] Various substituted imidazo[1,2a]pyridines reacted smoothly with 2-aminoheterocycles viz 2-aminopyridines, 2-aminoquinoline and 2aminopyrimidine under optimized conditions to afford corresponding aminomethylated products 45 in moderate to good yields.…”

Phenyliodine(III) Diacetate-Mediated 1,2-ipso-Migration in Mannich Bases of Imidazo[1,2-a]pyridines: Preparation of N-Acetoxymethyl/Alkoxymethyl-N-arylimidazo[1,2-a]pyridine-3-amines

“…White solid; 1.05 g, 59% yield; the eluent used was ethyl acetate/petroleum ether (6:4 v/v); mp = 160–162 °C (lit., 172.2–173.4 °C); 1 H NMR (400 MHz, CDCl 3 ): δ = 8.23 (d, J = 1.3 Hz, 1H), 8.11 (dd, J = 5.1, 1.1 Hz, 1H), 7.67–7.65 (m, 2H), 7.46 (dd, J = 9.5, 0.8 Hz, 1H), 7.44–7.40 (m, 1H), 7.37–7.30 (m, 3H), 7.08 (dd, J = 9.5, 2.0 Hz, 1H), 6.65–6.62 (m, 1H), 6.53 (d, J = 8.3 Hz, 1H), 5.21 (t, J = 5.1 Hz, 1H), 4.90 (d, J = 4.9 Hz, 2H) ppm; 13 C­{ 1 H} NMR (100 MHz, CDCl 3 ) δ = 158.1, 147.8, 145.1, 143.2, 137.4, 133.4, 128.6, 128.17, 128.10, 126.1, 122.5, 120.5, 117.9, 117.4, 113.6, 108.5, 35.4 ppm; HRMS (ESI) calcd for C 19 H 16 ClN 4 + [M + H] + 335.1058, found 335.1056.…”