Oxidative Difunctionalization of 2-Amino-4H-pyrans in Iodobenzene Diacetate and N-Chlorosuccinimide: Reactivity, Mechanistic Insights, and DFT Calculations

Abstract

Oxidative difunctionalization of 2-amino-4H-pyrans was accomplished with iodobenzene diacetate (IBD) and N-chlorosuccinimide (NCS) reagents in alcoholic medium. 2-Amino-4H-pyrans undergo geminal dialkoxylation with the migration of an amino group (1a,b, 2a-i, 3a,b, and 4) in IBD, whereas with NCS addition of both chlorine and alkoxy groups takes place across the chromene double bond (6a-i).

“One-pot” access to dihydrofurans via tandem oxidative difunctionalization and ring contraction of aminopyrans

“…Initially aminopyran undergoes oxidative difunctionalization with NCS in the presence of an alcohol solvent. 12 Subsequent addition of base to the aminopyran leads to proton abstraction from the amino group. This leads to a cascade pyran ring opening by the cleavage of the (C 2 -O 1 ) bond, and ring closure of the (O 1 -C 3 ) bond to dihydrofuran via elimination of HCl.…”

“…All the substrates 1(a-i) were prepared according to our reported procedure. 12 Compound 1j was prepared according to the procedure reported in literature. 18 General procedure for the synthesis of compounds 3(a-n).…”

“…From highly functionalized pyran derivatives: to the highly functionalized pyran analog 12 [5 mmol], in ethanol (10 mL), piperidine (6 mmol) was added at room temperature. The reaction mixture was stirred at room temperature, till the product is completely precipitated out.…”

“…Methyl 2-cyano-1-(4-cyanophenyl)-1,2-dihydronaphtho[2,1-b]furan-2-carboxylate (12). Yield: 0.343 g (97%); mp 188-190 °C; IR (neat, cm −1 ) 2957, 2228, 1767, 1251, 1051, 751; 1 H NMR (300 MHz, CDCl 3 ) δ: 7.92 (d,J = 9.0 Hz,1H),1H),7.68 (d,J = 8.5 Hz,2H),5H),7.10 (d,J = 7.4 Hz, 1H), 5.52 (s, 1H), 3.99 (s, 3H); 13 C NMR (75 MHz, CDCl 3 ) δ: 165.4, 155.7, 141.5, 132.9, 132.2, 130.7, 129.6, 129.2, 127.9, 124.5, 122.4, 118.2, 116.1, 113.3, 113.1, 111.7, 84.1, 57.0, 54.9; MS (ESI): m/z 377 (M + Na) + ; HRMS ESI (M + H) + m/z calcd for C 22 H 16 N 3 O 2 (M + Na) + 377.0902, found 377.0900.…”

“…Recently a mild method for oxidative difunctionalization of 2-amino-4H-pyrans has been developed by our group employing iodobenzene diacetate (IBD) and N-chlorosuccinimide (NCS) in an alcoholic medium. 12 Herein 2-amino-4H-pyrans are shown to undergo geminal dialkoxylation with an unusual 1,2-amino migration in the presence of iodobenzene diacetate and addition of chlorine and alkoxy groups takes place across the chromene double bond when NCS is employed.…”