Cyclization nitrogen radical

Competition between cyclization of the intermediate a-radical or further reduction is illustrated with the benzanilide substrates 50 [165], In all, four types of product are formed. Cyclization of the phenyl radical to a six-ring radical intermediate leads to the cyclization product 51. Cyclization of the phenyl radical to a five-ring radical intermediate leads to the diphenyl 52 after a further electron transfer step. Reduction of the aryl o-radical before cyclization gives 51, X = H. Cleavage of the carbonyl-nitrogen bond in the radical-anion affords a trace of the aniline S3. 

Cyclization of selenoimidates.a Reaction of the selenoimidate 1 with Bu3SnH (AIBN) generates an imidoyl radical that cyclizes to the nitrile 2 and the imine 3 of a chromanone. Only 3 is obtained if the benzyl substituent on nitrogen is changed to an alkyl group. The reaction follows a different course when an N-tolyl selenoimidate (4) is the starting imine (equation I). 

Other groups have reported free-radical approaches to lycoranoids less richly decorated than 66. For example, Rigby has reported a short synthesis of ot-lycorane (67) via an aryl radical-enamide cyclization that constructs the C 2a-Ci2b bond [42]. Padwa focused on the same bond construction via an aryl radical-dihydroindole cyclization in his synthesis of anhydrolycorin-7-one (68) [43]. Both Zard [44] and Cossy [45] have reported syntheses of y-lycorane (69) that involve initial construction of the N-Ci2a bond via cyclization of nitrogen-centered radicals. Both ap-... 

PhI(OAc)2 in trifluoroethanol and in the presence of carbonate base within rather short reaction time and displays a remarkably large substrate scope. Mechanistically, the authors propose an iititial interaction between the hypervalent iodine(lll) reagent and the amidine nitrogen, which upon homolytic cleavage of the N-1 bond initiates the start of a radical-based cyclization onto the arene ring. The reaction can also be conducted as a catalytic transformation using 20 mol% of Phi as catalyst and mCPBA as terminal oxidant. For this transformation HFIP is the preferred solvent [11]. 

Construction of C-C bonds adjacent to nitrogen is an important aspect of alkaloid chemistry. A new approach to indolizidines and pyrrolizidines has been developed in which acylamino-radicals (139) cyclize to the required products. ... 

Cross-linked PVP can also be obtained by cross-linking the preformed polymer chemically (with persulfates, hydrazine, or peroxides) or with actinic radiation (63). This approach requires a source of free radicals capable of hydrogen abstraction from one or another of the labile hydrogens attached alpha to the pyrrohdone carbonyl or lactam nitrogen. The subsequently formed PVP radical can combine with another such radical to form a cross-link or undergo side reactions such as scission or cyclization (64,65), thus ... 

The majority of sequential radical reactions deal with cyclizations as the key steps. The constructions of carbocycles, oxygen, and nitrogen heterocycles using (TMSlsSiH as a mediator are many and represents the expansion and importance of these synthetic approaches. For example, Nicolaou and coworkers found that (TMSlsSiH serves as a superior reagent in the radical-based approach toward the synthesis of azadirachtin, an antifeedant agent currently used as an insecticide, and in other related systems. ° ° Here below we collected a number of reactions mostly from the recent work in the area of intramolecular reactions. 

Radical cyclization of dihydropyridones 108 provided piperidine derivatives 109 containing a trifluoromethyl group at the bridgehead position adjacent to nitrogen <96JOC(61)8826>. 

Several functional groups containing carbon-nitrogen double bonds can participate in radical cyclizations. Among these are oxime ethers, imines, and hydrazones.337 Hydrazones and oximes are somewhat more reactive than imines, evidently because the adjacent substituents can stabilize the radical center at nitrogen.338 Cyclization at these functional groups leads to amino- substituted products. 

Entries 20 to 23 involve additions to C=N double bonds in oxime ethers and hydrazones. These reactions result in installation of a nitrogen substituent on the newly formed rings. Entry 20 involves the addition of the triphenylstannyl radical to the terminal alkyne followed by cyclization of the resulting vinyl radical. The product can be proto-destannylated in good yield. The ring closure generates an anti relationship for the amino substituent, which is consistent with the TS shown below. 

Bowman and coworkers described another nice approach in this field combining one anionic and two radical cyclization steps (Scheme 2.160) [368], Thus, they were able to construct differenttypes of nitrogen-containing heterocycles such as annulated pyrrolidines 2-724 and spiropyrrolidines 2-726 as well as indolizidines as 2-729. 

An efficient methodology for the construction of pyrrolizidines and other polycyclic nitrogen heterocycles using a radical domino sequence has been revealed by Bowman and coworkers [46]. These authors employed sulfenamides as substrates, which easily form aminyl radicals by treatment with tributyltin hydride and AIBN. For instance, 3-101 smoothly underwent a twofold 5-exo-trig cyclization to give the tetracyclic pyrrolizidine product 3-105 in 90% yield (Scheme 3.26). As intermediates, the radicals 3-102 to 3-104 can be assumed. 

New cyclizations via photochemically generated aminyl radicals have been reported, including further examples of the Hofmann-Loeffler-Freytag reaction.313 Intramolecular addition of an aminyl radical, generated by photochemically induced nitrogen chlorine bond homoysis, is also accompanied by cyclization as illustrated by the conversion of the unsaturated N-chloroamide 378 to the pyrrolidine 379.314 Piperidine formation can also... 

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