Alkenyl radicals cyclization

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. 

Alkenyl radicals generated by intramolecular addition to a triple bond can add to a nearby double bond, resulting in a tandem cyclization process. 

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... 

Allenyl ethers are useful key building blocks for the synthesis of a-methylene-y-butyrolactones [129, 130], The synthesis of the antileukemic botryodiplodin was accomplished with the crucial steps briefly presented in Scheme 8.56. Bromoallenyl ethers 225 were easily prepared by base-induced isomerization from the corresponding /3-bromoalkyl alkynyl ether compounds and then subjected to electrophilic bro-mination with NBS. The resulting acetals 226 were converted into 2-alkoxy-3-methy-lenetetrahydrofurans 227 by dehydrohalogenation of the alkenyl bromide unit to an alkyne and subsequent radical cyclization employing tributyltin hydride [130],... 

Undoubtedly, further work will be necessary in order to get a solid background for silyl radical cyclizations. In particular, further investigations on the nature of the pendant alkenyl substituent as well as on the ring size and substituent effects on the silicon in the ring expansion can be expected in the future. 

Demethoxyerythratidinone (10), one of the simplest of the erythrina alkaloids, was isolated in 1973 by Barton et al. from Erythrina lithosperma [14]. A concise approach to such Erythrina alkaloids using a disfavored 5-endo-trig radical cyclization mediated by nickel powder was described by Zard and coworkers [15]. A-Alkenyl trichloroacetamide 7 was... 

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-... 

The copper complexed aminyl radical cyclization has been used as a key step in a short total synthesis of ( )-gephyrotoxin 223AB (60). The alkenyl substituted ALchloropiperidine 59 was stereoselectively cyclized to construct the indolizidine ring system (Scheme 17) (86JOC5043). Tribu-... 

Intramolecular cyclization of N-alkenyl-2-bromoindoles has been described. The formation of five as well as six-membered ring in the radical cyclization proceeds in good yield [95TL4857]. A novel intramolecular free radical aromatic ipso substitution reaction has been reported [95CC1353]. Treatment of 138 with tributyltin hydride generates an alkyl radical which attacks the alkene at the carbon bearing the sulfur substituent. This is followed by elimination of the sulfur substituent to provide the cyclized products 139 in moderate yields. The efficiency of the reaction is dependent on the size of the ring formed and on the sulfur substituent. 

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... 

The radical addition to 1-alkenyl or 1-alkynylboronic esters or amides took place extremely smoothly because the boron atom stabilizes the resulting ct-radical intermediates. Bu3SnH and PhSH predominated the trans-addition products 287 in the addition to 1-alkynylboronic amides at 90 °G, whereas Bu3SnH and Ph2Ph produced the m-addition products 288 at 0°C (>98% Equation (82)).455 Intramolecular addition to 1-alkenylboronic esters has been demonstrated in boron-tethered radical cyclization that provided 1,3- or 1,4-alkanediols 290 via oxidative workup (Equation (83)).456 Inter- and intramolecular additions of alkyl radical457 and sulfonyl radical458 have also been studied. 

A-(4-Pentenyl)iodoacetamides (i.e., 142 and 145) underwent atom transfer radical cyclization reactions in the presence of trifluoroborate etherate at room temperature, usually with an excellent 8-endo regioselectivity (Schemes 59 and 60 <2005JOC1539>). It was thus shown that 8-endo cyclization of iV-alkenyl a-carbamoyl radicals is an intrinsically favored process easily promoted by a Lewis acid, such as BF3-OEt2. 

Similar methodology was employed to the synthesis of more complex polycyclic ring system, as shown in Scheme 32 <1997TL9069>. The initial alkenyl radical 54, formed by an intramolecular radical 13-< 4t>-dig macro-cyclization, initiated a radical cascade reaction by first reacting at the a-position of the furan ring. 

An interesting observation was made in the case of the 5-exo dig radical cyclization of the glucosyl pyridyl sulfone derivative 6 (Fig. 9b). An ( ) (Z)-stereoselectivity of greater than 50 1 was observed in the product, which was a fourfold increase in selectivity, compared with the previously reported tin hydride method. Closer examination of this reaction revealed that the stabilized vinylic radical was reduced to an alkenyl organosamarium species, as shown by a remarkably high incorporation of deuterium at this position (91%) when the reaction was performed in the presence of MeOD (Fig. 12). Compared with other studies on similar reductions of stabilized alkenyl radicals, this... 

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. 

An efficient way of introducing selenium in a radical precursor is the use of selenium containing building blocks. The selenides are particularly appropriate when the reaction sequence involves reaction steps that are incompatible with halides or when the corresponding halides are not stable. In Eq. (7), preparation of the selenenylated alkenyl sulfoxide 35 by alkylation of malonate 33 with the bromide 34 is described [18]. This procedure is not feasible with the corresponding halide due to cyclopropane formation via intramolecular alkylation. Radical cyclization of 35 in a 5-exo mode affords, after elimination of the phenylsulfinyl radical, the methylenecyclopentane 36 in good yield and excellent enantioselec-tivity. 

For unsubstituted alkenyl radicals containing up to eight carbons, with the general structure previously shown, the preferred mode of cyclization is exo. (The symbol at means that the alkene is at the terminus distant from the radical.) The reaction is controlled kinetically the major product is the one that forms faster. The rates of formation of the two possible adducts are a result of the stereochemical requirements of their transition states. Often the endo product is more stable than the exo product. When this is the case, however, the more stable product is not the major product formed. 

The feasibility of the use of acylphosphonates as a carbonyl group radical acceptor have been demonstrated. Radical cyclization of the acylphosphonate (418) in the presence of hexamethylditin gave the cyclopentanone (419) in 91% yield. Additionally, various electrophilic alkyl radicals from activated olefins bearing a-electron-withdrawing groups smoothly reacted with alkenyl acylphosphonates (420). Furthermore, similar results were obtained with al-kynylarylphosphonates (421) (Scheme 99). " ... 

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