Synthesis of 2‐methylthioindolizine‐3‐carbonitriles using nitro ketene dithioacetal

Abstract

The reaction of 1‐cyanomethylpyridinium chloride or bromide, 1a‐i, with 1,1‐bis(methylthio)‐2‐nitroethylene (2) in the presence of triethylamine as a base in ethanol gave the corresponding 2‐methylthioindolizine‐3‐carbonitrile 3 and 2‐methyl‐thio‐1‐nitroindolizine‐3‐carbonitrile 4 in good yields, respectively. Compounds 3a,f were key intermediates for the synthesis of cycl[3.2.2]azine derivatives.

Switching the reactivity of cyanomethylpyridinium salts in the 1,3-cycloaddition conditions with alkyl propiolates to cyanoindolizines or cyanoazaindolizinyl-indolizines

“…First, cycloimmonium salts 2a-f were easily prepared in good to excellent yields (58-97%) by reaction of pyridines 1a-f with chloroacetonitrile in acetonitrile at rt (Scheme 3). Salts 2a-c and 2e were previously reported [19][20][21][22] while salts 2d and 2f are newly synthesized compounds. Next, salts 2a-f were treated with TEA in acetonitrile/DMF mixture and alkyl propiolate to construct the 3-cyanoindolizines 3a-f (Scheme 3).…”

“…The mixture was magnetically stirred at rt for 48 h. The precipitate formed has been filtered, washed with acetone and dried to provide the pure 1-(cyanomethyl)pyridinium salt 2a-f. Salts 2a-c and 2e had the same physico-chemical characteristics as previously reported. [19][20][21][22] 1-(Cyanomethyl)-4-methoxypyridinium chloride (2d). The general procedure A was used with 3.22 g (29.5 mmol) of 4-methoxypyridine and 2.42 mL (38.3 mmol) chloroacetonitrile in 40 mL acetonitrile.…”

Indolizines and Their Hetero/Benzo Derivatives in Reactions of [8+2] Cycloaddition

“…3-Cyanindolizine 36a and its 6,8-dimethyl analog 36b with DMAD in refluxing toluene gave expected cyclazines, though in presence of Pd-C ( Scheme 16 , Table 8 ). The later group of Tominaga converted 2-MeS-derivatives of 3-CN-indolizines- 37a,b to MeS-cyclazines (again in the presence of the same catalyst) [ 59 ] ( Scheme 16 , Table 8 ).…”

Convenient Synthesis of 2-Aryl-1-haloindolizines from Pyridinium Salts and 2-Aryl-1,1-dihaloalk-1-enes

“…Pyridinium salts and 1,1-dihaloalk-1enes were prepared according to literature procedures. [19][20][21][22] 2-Aryl-1-haloindolizines 3; General Procedure A mixture of the pyridinium salt (0.15 mmol), the 1,1-dihaloalk-1ene (0.30 mmol), and DBU (0.675 mmol) in THF was placed in a sealed tube. The tube was heated at 90 °C for 12 h using an oil bath.…”