Reduction of arenediazonium salts by tetrakis(dimethylamino)ethylene (TDAE): efficient formation of products derived from aryl radicals

Abstract

Tetrakis(dimethylamino)ethylene (TDAE 1), has been exploited for the first time as a mild reagent for the reduction of arenediazonium salts to aryl radical intermediates through a single electron transfer (SET) pathway. Cyclization of the aryl radicals produced in this way led, in appropriate substrates, to syntheses of indolines and indoles. Cascade radical cyclizations of aryl radicals derived from arenediazonium salts are also reported. The relative ease of removal of the oxidized by-products of TDAE from the reaction mixture makes the methodology synthetically attractive.

Keywords: cyclization; electron transfer; indole; indoline; radical.

Scheme 1

Aza- and thia-substituted electron donors.

Scheme 2

Radical-polar crossover reaction of arenediazonium salts by TTF.

Scheme 3

Studies on the reductive radical cyclization of arenediazonium salt 16 by TDAE.

Scheme 4

Preparation of the arenediazonium salts 31a–d. Reagents and conditions: (a) 23, NaH, THF, 0 °C, 0.5 h, then TBDPS-Cl, 0 °C to 25 °C, 4 h, 85%; (b) 25, DIAD, PPh₃, THF, 0 °C to 25 °C, 12 h, 80% (26a), 64% (26d); (c) TBAF, THF, 25 °C, 1.5 h, 85% (27a), 0.5 h, 97% (27d); (d) PBr₃, DCM, 0 °C to 25 °C, 1 h, 99% (28a), 93% (28d); (e) PhSH, NaH, THF, 0 °C to 25 °C, 1 h, then 28, 25 °C, 5 h, 98% (29a), 94% (29d); (f) Cu(acac)₂, NaBH₄, EtOH, 25 °C, 15 h, 70% (30a), SnCl₂·2H₂O, MeOH, 65 °C, 4 h, 91% (30d); (g) NOBF₄, CH₂Cl₂, −20 °C to −10 °C, 1.5 h, 98% (31a), 100% (31d); (h) NaIO₄, MeOH/H₂O, r.t., 1 h 15 min, 92%; (i) SnCl₂, MeOH, 65 °C, 4 h, 71%; (j) NOBF₄, CH₂Cl₂, −20 °C to −10 °C, 1.5 h, 100%; (k) NaIO₄, MeOH/H₂O (1:1), r.t., 72 h, 82%; (l) SnCl₂·2H₂O, MeOH, 3.5 h, 83%; (m) NOBF₄, CH₂Cl₂, −20 °C to −10 °C, 1.5 h, 100%.

Scheme 5

Cascade radical cyclizations of arenediazonium salts 42 and 44 by TDAE. Reagents and conditions: (a) 23, NaH, THF, 0 °C, 0.5 h, then TBDPS-Cl, 0 °C to 25 °C, 4 h, 85%; (b) NBS, Me₂S, CH₂Cl₂, −30 °C, 0.5 h, then 24, −30 °C to r.t., 3 h, 95%; (c) 23, NaH, THF, 0 °C to r.t., 1 h, then 34, 72 h, 61%; (d) N-(2-nitrophenyl)methanesulfonamide (25a), DIAD, PPh₃, THF, 0 °C to r.t., 1 h, 98%; (e) TBAF, THF, r.t., 20 min, 90%; (f) NBS, PPh₃, CH₂Cl₂, −25 °C, 20 min, then 37, −25 °C to r.t., 40 min, 96%; (g) PhSH, NaH, THF, 0 °C to r.t., 1 h, then 38, r.t., 12 h, 86%; (h) NaIO₄, H₂O, MeOH, r.t., 76 h, 73%; (i) SnCl₂, CH₃OH, H₂O, reflux, 3.5 h to 4 h, 95% (41), 78% (43); (j) NOBF₄, CH₂Cl₂, −15 °C to 0 °C, 1.5 h; (k) NOBF₄, CH₂Cl₂, −15 °C to 0 °C, 1.5 h; (l) TDAE (1.0 equiv), acetone, 10 min, r.t., 85% 47, 46% 33, 52% 21 in two steps, from 41; 77% 47, 46% 21 in two steps, from 43.

Scheme 6

TDAE-mediated radical based addition-elimination route to indoles.

Scheme 7

Cyclization of the arenediazonium salts 49b–d by TDAE. Reagents and conditions: (a) NOBF₄, CH₂Cl₂, −10 °C to 0 °C, 1.5 h; (b) TDAE (1.5 equiv), anhydrous DMF, r.t., 10 min; (c) p-toluenesulfonic acid monohydrate, CH₂Cl₂, r.t., 12 h, 63% (51b, in three steps from 48b), 43% (51c, in three steps from 48c); (d) NOBF₄, CH₂Cl₂, −10 °C to 0 °C, 1.5 h; (e) TDAE (1.5 equiv), anhydrous DMF, r.t., 10 min, 74% 50d; (f) p-toluenesulfonic acid monohydrate, CH₂Cl₂, r.t., 12 h, 64% (overall yield in three steps, from 48d).

Scheme 8

Cyclization of the arenediazonium salt 62 by TDAE. Reagents and conditions: (a) 2-Nitrobenzenesulfonyl chloride, DMAP, pyridine, 0 °C then 110 °C, 27 h, 57%; (b) H₂, Pd/C, EtOAc, 3 h, 98%; (c) 61, NOBF₄, CH₂Cl₂, −10 °C, 1.5 h, 95%; (d) TDAE, CH₃OH/acetone (1:1), 25 °C, 10 min, 33% 63, 5% 64, 60% 65.

Scheme 9

Mechanism for the formation of the tetracyclic sulfonamide 65.

Scheme 10

Possible mechanism for the formation of indole (63) and indole sulfonamide 64.