Group-transfer cyclization

Bis-acceptor-substituted diazomethanes are most conveniently prepared by diazo group transfer to CH acidic compounds either with sulfonyl azides under basic conditions [949,950] or with l-alkyl-2-azidopyridinium salts [951] under neutral or acidic conditions [952-954]. Diazo group transfer with both types of reagents usually proceeds in high yield with malonic acid derivatives, 3-keto esters and amides, 1,3-diketones, or p, y-unsaturated carbonyl compounds [955,956]. Cyano-, sulfonyl, or nitrodiazomethanes, which can be unstable or sensitive to bases, can often only be prepared with 2-azidopyridinium salts, which accomplish diazo group transfer under neutral or slightly acidic reaction conditions. Other problematic substrates include amides of the type Z-CHj-CONHR and P-imino esters or the tautomeric 3-amino-2-propenoic esters, which upon diazo group transfer cyclize to 1,2,3-triazoles [957-959]. 

The allyloxy and propargyloxy compounds are easily prepared by the opening of mono-substituted epoxides with sodium aryl tellurolates, followed by allylation and propargyla-tion of the obtained -hydroxytellurides, submitted to irradiation with a sun lamp in the presence of hexabutylditin, and suffer group-transfer cyclization under 5-exo-mode to give the 2,4-disubstituted tetrahydrofuran derivatives. ... 

An alternative to reductive radical cyclization procedures is the use of group transfer methods. A novel group transfer cyclization reaction involving an organotellurium compound 47 has been described [95CC2515]. The bicyclic product 48 is formed as a 2 1 mixture of isomers at the terminus. 

Scheme 6. PET induced phenylseleno group transfer cyclizations...

Because sp carbon-tellurium bonds are often unstable under photoirradiation conditions, carbotelluration producing sp -carbon-tellurium bonds occurs preferentially. Successful telluro group transfer cyclization has also been reported [119g]. Carbonyl tellurides are useful precursors for carbonyl radicals, which are employed for cyclization and addition reactions [127]. The reaction of diorganyl tellurides wifh isocyanides leads to fhe formation of imidoyl tellurides in high yields [128]. The carbotelluration system has also recenfly been applied to living radical polymerization (Scheme 15.52) [129]. 

A series of primary and secondary alkyl aryl tellurides has been found to undergo rapid (3-10 min) group-transfer cyclization to afford tetrahydrofuran derivatives in good yields (60-74%) under micro vave heating conditions at 250 °C in ethylene glycol or at 180 °C in vater, the only dra vback of the process being the loss in dia-steroselectivity as a consequence of the higher reaction temperature [22]. Li and coworkers have developed a successful method for synthesis of vinyl cycloethers by direct addition of THF and 1,4-dioxane to alkynes reaction occurs at 200 °C in 40-180 min under the action of microwave irradiation (300 W) [23]. 

Appropriately substituted selenides can undergo cyclization reactions via a group transfer process. 

Various transition metals have been used in redox processes. For example, tandem sequences of cyclization have been initiated from malonate enolates by electron-transfer-induced oxidation with ferricenium ion Cp2pe+ (51) followed by cyclization and either radical or cationic termination (Scheme 41). ° Titanium, in the form of Cp2TiPh, has been used to initiate reductive radical cyclizations to give y- and 5-cyano esters in a 5- or 6-exo manner, respectively (Scheme 42). The Ti(III) reagent coordinates both to the C=0 and CN groups and cyclization proceeds irreversibly without formation of iminyl radical intermediates.The oxidation of benzylic and allylic alcohols in a two-phase system in the presence of r-butyl hydroperoxide, a copper catalyst, and a phase-transfer catalyst has been examined. The reactions were shown to proceed via a heterolytic mechanism however, the oxidations of related active methylene compounds (without the alcohol functionality) were determined to be free-radical processes. 

Typical procedure for group-transfer radical cyclization preparation of compound 3bP (Ar = p-CF3CgH4) To a solution of 2-(allyloxy)cyclohexyl 4-(trifluoromethyl)phenyl... 

The syntheses shown in Scheme 26 (71CB1573) are based on dibenzo-/3-tropolone (108) and its enamines. Condensation of 108 and benzoin in the presence of ammonia affords pyrrole 109. The morpholino enamine gives pyrazole 110 via benzoylation, hydrolytic elimination of morpholine, and cyclization, whereas diazo-group transfer onto the anilino enamine leads to triazole 111. Dione 108 and p-nitrophenylazide in one step give predominantly the p-nitro derivative of 111 (92G249). 

Diazoamides of type 300 rapidly cyclize to form aziridines 302 (342) (Scheme 8.73). It is conceivable that this reaction proceeds through a 1,2,3-triazoline intermediate 301, which is the consequence of a LUMO(dipole)— HOMO(dipolarophile) controlled intramolecular [3 + 2] cycloaddition. Some remarkable steric effects were encountered for this cyclization. While the piperidine derivative [300, = ( 112)4] readily cyclized by diazo group transfer at... 

Intramolecular group-transfer reactions can involve either direct displacements or addition-fragmentation reactions that are discussed in Section 4.2.4. A direct displacement is shown in the reaction of aryl radical 1, produced from the corresponding bromide. Cyclization of 1 is fast enough to compete efficiently... 

Considerable ingenuity was required in both the synthesis of these chiral compounds695 697 and the stereochemical analysis of the products formed from them by enzymes.698 700 In one experiment the phospho group was transferred from chiral phenyl phosphate to a diol acceptor using E. coli alkaline phosphatase as a catalyst (Eq. 12-36). In this reaction transfer of the phospho group occurred without inversion. The chirality of the product was determined as follows. It was cyclized by a nonenzymatic in-line displacement to give equimolar ratios of three isomeric cyclic diesters. These were methylated with diazomethane to a mixture of three pairs of diastereoisomers triesters. These dia-stereoisomers were separated and the chirality was determined by a sophisticated mass spectrometric analysis.692 A simpler analysis employs 31P NMR spectroscopy and is illustrated in Fig. 12-22. Since alkaline phosphatase is relatively nonspecific, most phosphate esters produced by the action of phosphotransferases can have their phospho groups transferred without inversion to 1,2-propanediol and the chirality can be determined by this method. 

However, Samsel and Kochi concluded from a detailed mechanistic study that a chain mechanism analogous to group transfer (rather than radical-cobalt coupling) was operative in the cyclization of hexenylcobalt compounds to cyclopentylmethyl isomers. E. G. Samsel and J. K. Kochi, J. Am. Chem. Soc., 1986,108, 4790. 

Iodocarbonyls are excellent substrates for atom transfer cyclization, as shown by examples from our recent work in Scheme 29.19-129 When two carbonyl (or cyano) groups are present, bromides can also serve as radical precursors. Photolysis with 10% ditin usually provides excellent yields of kinetic products at high concentration, and alkene substituents often dictate the regioselectivity. The y-iodo ester products are particularly versatile for subsequent transformations, which can often be conducted in situ. Although tertiary iodine products sometimes go on to give lactones or alkenes, primary and secondary iodides can often be isolated if desired. The last example is particularly noteworthy the kinetic product from the cyclization presented in Scheme 27 is trapped, because bromine atom transfer is much more rapid that reverse cyclization. 

Cyclizations of aromatic diazonium salts138 (intramolecular Meerwein arylations) are pieparatively related to atom transfer reactions because a radical cyclization is terminated by the transfer of an atom or group other than hydrogen. However, the two methods are not mechanistically related. In the atom transfer method, the atom that is transferred to the cyclic product always derives from the radical precursor, but in the cyclizations of aryldiazonium salts, die atom or group transferred derives from an added reagent. This means that many different products can be prepared from a single diazonium precursor, but it... 

Figure 8.4 PhSe-group transfer radical cyclization reaction.

To achieve low radical concentrations, most radical reactions are traditionally performed as chain reactions. Atom or group transfer reactions are one of the two basic chain modes. In this process the atom or group X is the chain carrier. A metal complex can promote such chain reactions in two ways. On one hand, the catalyst acts only to initiate the chain process by generating the initial radical 29A from substrate 29 (Fig. 10). This intermediate undergoes the typical radical reactions, such as additions or cyclizations leading to radical 29B, which stabilizes to product 30 by abstracting the group X from 29. A typical example is the use of catalytic amounts of cobalt(II) salts in oxidative radical reactions catalyzed by /V-hydroxyphthalimide (NHPI), which is the chain carrier [102]. 

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