Cyclization, of alkenyl radicals

Recently, radicals have increasingly been used in organic synthesis, especially for cyclization of alkenyl radicals generated tfom the corresponding halides Tin hydrides have been used for this purpose before but (Me3Si)3SiH is now used because it is environmentally safer. 

This section will be devoted to cyclization of alkenyl radicals... 

Electrophilic radical cyclizations of alkenyl aminium cation radicals have shown synthetic utility. Hofmann-Loffler-Freytag reactions do not compete with 5-exo cyclizations (75BSF1429). The homolytic cyclization of Af-chloroalkenylamines under acidic or Lewis acidic conditions has been studied primarily by Surzur and Stella, and the chemistry of these precursors for electrophilic aminyl radical generation has been reviewed [83AG(E)337]. Radical chain reactions can be initiated by heat, UV photol-... 

Alcaide s group has reported further work on the radical cyclization of alkenyl or alkynyl substituted 4-allenynol-/)-lactams (see Section 2.04.9.6) <2007JOC1604>. Titanocene monochloride mediated reductive radical cyclization of l-cyanoalkyl-4-(epoxy-2-phenylethyl)-2-azetidinones yielded bi- or tri-cyclic /3-lactams, the latter having an aryl group fused to a seven membered ring <2007T3017>. 

Radical cyclization of alkenyl iodide 350 provides a route to a tetrahydropyan 351 bearing an exocyclic moiety (Equation 148) <20000L2011>. 

These cobaloximes (1) are generated by reaction of alkyl halides with in situ generated Co (dmgH)2py. They are orange crystals that are relatively stable to air and silica gel, but on photolysis they generate R-, which can be trapped in generally high yield or which cyclize in the case of alkenyl radicals.1... 

Kinetic data for the 5-exo cyclization of alkyl radical additions to the yV-aziridinylimino groups were obtained by competitive 5-exo cyclization to the A-aziridinylimino group versus an alkenyl group (Eq. 15). Reaction of compound 59 with BujSnH in benzene at 20 °C at 350 nm yielded only 61. Apparently, the primary alkyl radical... 

Similarly, at a carbon anode in 1 1 MeOH-THF, anodic cyclization of allylsilane enol ether (XCIX) proceeded stereoselectively to give (C) [Eq. (63)]. The use of allyl silanes as the unsaturated nucleophilic component in such radical-cation cyclizations proved to be beneficial, though the exact mechanistic details remain somewhat speculative [147]. The method represents an improvement over earlier methods involving anodic cyclization of alkenyl-substituted enol acetates [148]. 

The Barton nitrite ester photolysis is undeniably one of the most popular and useful reactions in radical chemistry for the functionalization of remote and inactivated positions within steroids (Scheme 19). Photolysis of nitrite esters gives nitric oxide and an alkoxyl radical that abstracts an ideally positioned hydrogen atom (1,5-hydrogen atom abstraction). The resulting alkyl radical reacts with nitric oxide in a solvent cage to afford the nitroso-alcohol derivative that is finally isolated as an oxime [53]. Related cyclizations of alkoxyl radicals have been reported by Surzur photolysis of y,(5-alkenyl nitrite esters leads to alkoxyl radicals that undergo subsequent tandem 5-exo cyclization followed by NO-trapping [54, 55]. 

Scheme 39. Translocation of alkenyl radicals followed by 5-exo-trig cyclization...

Throughout the course of their investigation of vinyl radical cyclization using A -alkenyl-7-bromo-substituted hexahydroindolinones, Padwa synthesized a pyrido [3,2,l-/ ]carbazolonone (53) in 81% yield as a result of cyclization of the radical onto the benzene ring [44]. 

Negishi, E.-i., Ma, S., Sugihara, T. and Noda, Y. (1997) Synthesis of hydrazulenes via Zr-promoted bicyclization of enynes and transition metal-catalyzed or radical cyclization of alkenyl iodides. Efficient synthesis of ( )-7-e/n -)3-bulnesene. J. Org. Chem., 62,1922-3. 

The fact that the cyclization is directed toward an acetylenic group and leads to formation of an alkenyl radical is significant. Formation of a saturated iodide could lead to a more complex product mixture because the cyclized product could undergo iodine atom transfer and proceed to add to a second unsaturated center. Vinyl iodides are much less reactive and the reaction product is unreactive. Owing to the potential... 

Alkenyl radicals generated by addition of trialkylstannyl radicals to terminal alkynes can undergo cyclization with a nearby double bond. 

Radical cyclization of N-alkenylamino acid derivatives Proline derivatives can be obtained by cyclization of N-alkenyl amino acid derivatives. Thus the (3-iodo allylic amine 2, prepared in 54% yield from threonine, cyclizes in the presence... 

Recently it has been shown that radical anionic cyclization of olefinic enones effectively compete with intramolecular [2 -I- 2]-cycloaddition to form spirocy-clic compounds [205, 206], 3-Alkenyloxy- and 3-alkenyl-2-cyclohexenones 235 are irradiated in the presence of triethylamine. As depicted in Scheme 46 two reaction pathways may operate. Both involve electron transfer steps, either to the starting material (resulting in a direct cyclization) or to the preformed cyclobutane derivative 239, which undergoes reductive cleavage. The second... 

A more comprehensive study on the behavior of 5-acetylenic iodides in the presence of zinc was later reported21 and clearly revealed that when iodide 14 was treated with acid-washed zinc (pre-treated with Mel for activation and removal of traces of moisture) in a mixture of benzene and DMF, the acyclic organozinc iodide 21 and the cyclic vinyl iodide 22 were both produced. The amount of 22 increased significantly when the reaction mixture was sonicated rather than stirred or if a zinc-copper couple was used. The accumulation of compound 22 was consistent with its inability to be converted to an alkenyl organozinc species by reaction with metallic zinc under these conditions. However, no substantial cyclization of the open-chain organozinc 21 was observed. The formation of the five-membered ring compound 22 was attributed to a free-radical process... 

Reaction of alkylthiyl radicals with alkenyl cyclopropanes (44) furnishes intermediate radicals (45) after addition and ring opening. Addition of a further radical acceptor leads to tricyclic [5,5, ] systems via addition followed by cyclization and elimination (Scheme 17).52... 

The absolute structure of (-)-(M)-39 and the major isomer (+)-(IS, 4R)-4( was determined by X-ray structural analysis using an anomalous scattering method (Figure 4-a and Figure 4-b). Figure 5 shows the superimposed structure of both absolute structures which was drawn with the overlay program included in CSC Chem3D. The sulfur and the alkenyl carbon atoms are closely placed to make the C-S bond easily, and subsequent cyclization of biradical BR needs the rotation of the radical center like path a to yield (1S,4R)-40. The molecular transformation from (-)-39 to (+)-40 needs... 

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