Silver-Catalyzed, Aldehyde-Induced α-C–H Functionalization of Tetrahydroisoquinolines with Concurrent C–P Bond Formation/N-Alkylation

Abstract

The first facile and efficient silver-catalyzed, aldehyde-induced three-component reaction of N-unprotected tetrahydroisoquinolines, aldehydes, and dialkyl phosphonates has been developed, providing a general one-step approach to structurally diverse C1-phosphonylated THIQs accompanied by concurrent C-P bond formation/N-alkylation with remarkable functional group tolerance and excellent regioselectivity for endo products.

Practical Synthesis of 1,2,3,4-Tetrahydroisoquinoline-1-phosphonic and -1-phosphinic Acids through Kabachnik–Fields and Aza-Pudovik Reaction

“…After this time, the mixture was heated at 85 °C for 1 h. The crude product was purified by flash chromatography (EtOAc:hexane, 95:5), giving compound 6 (0.25 g, 74%) as a yellow oil. The spectroscopic 1 H, 13 C, and 31 P NMR data are similar to those reported previously. 13…”

“…After this time, triethyl phosphite (0.17 g, 0.18 mL, 1.03 mmol) was added, and the reaction mixture was stirred at 60 °C for 24.0 h. The crude product was purified by flash chromatography (EtOAc:MeOH, 95:5), giving compound 8 (0.18 g, 70%) as a colorless oil. The spectroscopic 1 H, 13 C, and 31 P NMR data are similar to those reported previously. 15 From 9: A solution of imine 9 (0.10 g, 0.76 mmol) in MeCN (3 mL) was treated with phenylboronic acid (10 mg, 0.07 mmol) and diethyl phosphite (0.12 g, 0.11 mL, 0.84 mmol).…”

“…Based on our previous experience in the preparation of acyclic -aminophosphonates via 'one-pot' three-component reactions, 11 initially we proposed the synthesis of 1,2,3,4-tetrahydroisoquinoline-1-phosphonate 6 using 2-(2-bromoethyl)benzaldehyde (5) as starting material, which was easily obtained from isochroman. 12 Thus, the Kabachnik-Fields reaction of benzaldehyde 5 with benzylamine and dimethyl phosphite in the presence of phenylboronic acid (PhB(OH) 2 ) as catalyst (MeCN, 85 °C, 1.0 h) gave dimethyl 2-benzyl-1,2,3,4-tetrahydroisoquinoline-1-phosphonate (6) in 74% yield 13,14 which, by hydrogenolysis of the N-Bn bond with hydrogen (5 atm) using 20% Pd/C as catalyst (MeOH, 50 °C, 24.0 h), afforded the cyclic -aminophosphonate 7 in 32% yield (Scheme 2).…”

Synthesis, Spectroscopic Characterization, and In Vitro Antibacterial Evaluation of Novel Functionalized Sulfamidocarbonyloxyphosphonates

“…The two methoxy groups of the phosphonate appeared as two separate doublets ( 3 J H-P ~10 Hz) at 3.5 and 3.7 ppm, while the NH of the carbamate appeared as a broad singlet at δ 8–11 ppm. The 13 C spectrum was also characteristic due to the expected doublets related to the presence of the phosphorus ( J C-P couplings): (i) the methoxy of the phosphonates at 54 ppm ( 2 J C-P ~7–8 Hz), and (ii) the aromatic ring ( 3 J C-P ~6 Hz and 4 J C-P ~1–3 Hz) [ 35 , 36 ]. The 13 C chemical shifts are particular, as the carbonyl of the carbamate at 150 ppm (doublet with a 3 J C-P = 12 Hz coupling constant) and the greatly deshielded COO C H(Ph)POOR carbon at 70 ppm (doublet with a 1 J C-P = 170 Hz coupling constant).…”

Protective property of epoxy coatings containing polyaniline and laminar basalt in neutral, alkaline, and acidic media

“…[15] Recently, several strategies have been used to increase the effectiveness of PANI as protective coating on metals. Various nanoparticles, such as carbon nanotubes, [22] natural fibers, [23] LDHs, [24] montmorillonite (MMT), [25] graphite [12] etc., utilized as additives to enhance the mechanical and barrier performance of polymeric coatings, have been reported. [26][27][28][29] Large quantities of investigations demonstrate that protective coatings incorporated with platelike inorganic fillers usually exhibit substantial enhancement in physical and chemical properties, including thermal stability, flame retardance, barrier resistance, and stress corrosion prevention.…”