Intramolecular cascade radical cyclizations promoted by samarium diiodide

Samarium diiodide promotes intramolecular cascade radical cyclizations of cyanamide radical precursors conveniently to afford polycyclic N-heterocycles in moderate to good yields


Results and Discussion
Scheme 1 shows the synthesis of cyanamides 4. Condensation of 2-iodoaniline 1 with dimethyl cyanoimidodithiocarbonate 15 in the presence of Cs2CO3 in DMF at 100 °C gave adduct The cyano group is usually stable and cannot be reduced under radical conditions.7][18] However, substrates 4 containing cyano groups formed the intermediate radicals and cyclized to afford 7 in moderate to good yields under radical conditions with SmI2 (Scheme 2).The results are listed in Table 1.

Scheme 2. The intramolecular cascade radical cyclizations promoted by SmI2.
The polycyclic formation can be explained by the putative mechanism presented in Scheme 2. The aryl radicals 5 generated from the precursors 4 underwent a 6-exo-dig cyclization into the nitriles to give the intermediate radicals 6.The intermediates 6 further underwent a 6-endo-trig addition onto the unsaturated moiety and subsequent aromatization or reduction under the reaction conditions (SmI2-HMPA) to yield the corresponding polycyclic compounds 7.
The SmI2-mediated reduction of aryl iodide results in a carbon radical which is intramolecularly trapped by a cyanamide, which in turn is trapped by an alkene or a phenyl ring.This methodology is useful in building polycyclic systems in a single step.Moreover, this new process has some methodological advantages since samarium salts are easily eliminated from products.

Conclusions
In summary, polycyclic N-heterocycles can be conveniently prepared via SmI2-promoted intramolecular cascade radical cyclizations with cyanamides as radical precursors.

Experimental Section
General.Unless otherwise indicated, all reactions were carried out under a dry nitrogen atmosphere.DMF was freshly distilled from calcium hydride and THF was distilled from sodiumbenzophenone immediately prior to use.The other reagents were used directly without further purification.Melting points (mp) were obtained on a B-540 Büchi melting-point apparatus and are uncorrected. 1H NMR (400 MHz) and 13 C NMR (100 MHz) data were recorded on a DPX-400 instrument with CDCl3 or DMSO-d6 as solvent and tetramethylsilane (TMS) as the internal standard.Chemical shifts are given in ppm and spin-spin coupling constants, J, are given in Hz.
Mass spectra (MS) were recorded on a HP5989A mass spectrometer.Elemental analyses were carried out on a PE EA2400 CHN analyzer.

Synthesis of N-cyano-N'-(2-iodophenyl)formamidine (3).
To a solution of compound 2 (1.2 g, 3.8 mmol) in absolute ethanol (25 mL) was added Raney Nickel 2800 (1.2 g).The mixture was heated to reflux for 6 h and quickly filtered while it was still hot.The filtrate was concentrated to half its volume and the product was crystallized.The solid was filtered and dried in a vacuum container to afford 3 (0.75 g, 73%) as a white solid.Mp 166-168 °C;
The appropriate acyl chloride (0.3 mmol) in CH2Cl2 (3 mL) was added dropwise to the mixture at 0 °C.The mixture was stirred for 1 h at room temperature.The reaction was quenched with saturated NaHCO3 solution and then extracted with CH2Cl2.The organic layer was washed with water, brine and dried over Na2SO4.The filtrate was evaporated to dryness under reduced pressure, and the residue was purified by silica gel flash chromatography to give 4a-d.
Alkyl bromide (0.22 mmol) was added dropwise to the mixture.The mixture was stirred for 8 h at 50 °C.After filtration, the filtrate was concentrated and the residue was purified by silica gel flash chromatography to give 4e-g.

Table 1 .
The heterocyclic compounds 7 prepared by intramolecular cascade cyclizations with SmI2