Cyclization reactions 5-exo

The position of the alkene is crucial for efficient cyclization. Reactions of N-lithio-5-hexenamine led to only a trace of the piperidine from 6-exo cyclization. Reactions of N-lithio-3-butenylamine gave no cyclic products the acyclic amine and products most likely the result of /3-scission were obtained (87T281). 

The 5-exo cyclization reactions of hydrocarbon 5-hexenyl radicals comprise the most highly-studied of all cyclization processes, and such processes have been extensively and effectively exploited for synthetic purpose [176-179]. There... 

Chloro-l,6-heptadienes underwent alkylation/5-exo cyclization reactions in the presence of alkylaluminum reagents catalyzed by 5 mol% FeCl3 in the presence of PPI13 or DPEphos affording 2-alkylmethylenecyclopentanes in 30-80% yield. A polar two-electron mechanism was formulated for the reaction, but radicals may be involved [88]. 

Grigg reported tandem radical addition/5-exo cyclization reactions of bromotri-chloromethane and 1,6-dienes 169 catalyzed by 5 mol% Ru(PPh3)3Cl2 (Fig. 42). 

Giese and coworkers investigated radical 5-exo cyclization reactions of bromoacetaldehyde allyl acetals 264 (Y=0, R1=OBu) catalyzed by 251 and found that either product 265 or 266 results selectively, depending on the amount of catalyst (1-40 mol%) and the reducing conditions (entry 8) [304]. Mild reducing conditions, such as Zn in DMF or a potential of —0.8 V vs Ag/Ag+, and higher... 

S-Allyloxy tellurides also underwent similar radical 5-exo cyclizations catalyzed by 7 mol% of Ni(acac)2 and 2 equiv. of Et2Zn [113]. The reaction proceeded with high r/.v-selectivity in 56% yield. In contrast to the reactions of 5-hexenyl iodides shown above, 5-exo cyclization reactions of 5-hexynyl iodides were proposed to proceed by a two-electron pathway consisting of alkyne coordination/oxidative addition/intramolecular carbonickelation and reductive elimination, resulting in alkylidenecyclopentanes [114]. 

Recently, Chaminade and coworkers reported Ni-catalyzed electrochemically mediated radical 5-exo cyclization reactions of /V-allyl-a-bromo amides 116 (Fig. 28) [138]. Among the catalysts tested 98a and 98b were the best in DMF as the solvent, but the cyclized products 117 were obtained in moderate yields of. For /V,/V-diallylamides 116 (R2=Allyl), overreduction of the extra alkenyl unit competed under the reaction conditions. Using ethanol instead gave considerably better results and pyrrolidones 117 were isolated in 49-99% yield. Reduction of the allyl group could, however, not be prevented under these conditions. 

Katsumata and colleagues reported the first electrochemically mediated Ni(I)-catalyzed tandem radical cyclization reactions [139]. A bromoacetaldehyde dienyl acetal or the corresponding enynyl acetal underwent tandem 5-exo/5-exo cyclization reactions in the presence of Ni(cyclam) complex 98a under electrochemical reductive conditions (see Part 2, Sect. 5.3.3, Fig. 68). Bicyclic esters were isolated in 35% and 72% yields as a mixture of two and four diastereomers, respectively. 

In the same context, Bailey and Ovaska have described a tandem cyclization of an enynyl alkyllithium generated by low-temperature iodine-lithium exchange on iodide 269. Two sequential 5-exo cyclization reactions when warmed to room temperature afford... 

In this context aryllithiums are also able to carbolithiate a benzyne moiety, and so we have also described the preparation of several phenantridine, dibenzopyran and diben-zothiopyran derivatives 383. In these cases y-functionalized organolithiums, derived from bromides 382, afford the corresponding and regiospecifically functionalized six-membered benzofused N-, O- or S-heterocycles through a 6-exo cyclization reaction onto a benzyne intermediate (Scheme 101)161b. 

Arguably one of the synthetically most important applications of radical chemistry are 5-exo cyclization reactions [39]. Suitably substituted unsaturated epoxides are good substrates for these transformations as shown in Scheme 22. 

Formation of six-membered cycles is the second most common case of heterocyclic Mizoroki-Heck reactions, with, as for the formation of five-membered rings, exo-cyclization reactions being largely favoured compared to c d( -cyclization reactions. As already noted for the five-membered cycles, there are more examples of iV-heterocyclic formation than of oxygen-containing heterocycles. 

Radical cyclization continues to be one of the most popular radical reaction classes used in synthesis. By far the majority of published cyclization reactions are 5-exo in nature and this year is no exception. The rates of 5-exo cyclization reactions continue to be measured. For example, the rate constants for the 5-exo cyclizations of the 6,6-diphenylhex-5-enyl, 1-methyl-6,6-diphenylhex-5-enyl and the 1,1-dimethyl-6,6-diphenylhex-5-enyl radicals have been measured by laser flash photolysis studies and Arrhenius parameters determined. The relative rate constants for cyclization, and the reaction with PhSeH, were determined at 20 °C. At 20 °C the rates of the three primary, secondary and tertiary radicals with PhSeH were approximately (1.2 0.1) X 10 lmol s The rate constants for alkyl radicals calibrated by competition reactions with PhSeH and PhSH were found to be 30-40% smaller than previously reported and thus it was concluded that derived rate constants for some fast radical reactions may have to be adjusted accordingly. The rate constants for the 5-exo cyclization of secondary radicals on to hydrazones and oxime ethers have been determined. The fastest rate constants were observed for the IV-benzoylhydrazone acceptor. The rate constants were found to be approximately 800 times faster than for the corresponding 5-exo cyclization on to alkenes." Other work has measured the rate constants of cyclization of a range of fluorinated hex-5-enyl, hept-6-enyl, oct-7-enyl and non-8-enyl radicals. Not only were the rate constants measured but the regioselectivity of cyclization was compared with that for the aU-carbon homologues." The 6-exo cyclization of 1,1,2,2-tetrafluoro- and l,l,2,2,3,3,4,4-octafluorohept-6-enyl radicals were found to be approximately 10 times faster than those for the parent... 

Glorias developed a Rh(III)-catalyzed oxidative ortAo-olefination and exo-cyclization reaction for the synthesis of y-butyrolactam derivatives [19a]. The resulting data showed that only products with a Z-configured exocyclic C=C bond are formed. A representative transformation, in which benzamide and n-butyl acrylate generate 29 in 62% yield, is shown in the following (Eq. (5.28)). Similarly, Zhou and Li developed a Rh(lll)-catalyzed C-H bond activation and annulation of 0-methyl oximes with isocyanates for the synthesis of 3-methyleneisoindolin-l-ones 30 (Eq. (5.29)) [19b]. 

---