Endo cyclization reaction

The AgNOs-catalyzed 5-endo cyclization reactions of al-lenic amino acids proceeds in acetone at room temperature to give the corresponding 2,5-dihydro-l//-pyrroles with... 

Phenolic oxygen participates in facile oxypalladation. The intramolecular reaction of 2-hydroxychalcone (105) produces the flavone 106[127]. The ben-zofuran 107 is formed from 2-allyIphenol by exo cyclization with Pd(OAc)2, but benzopyran 108 is obtained by endo cyclization with PdChf S], Normal cyclization takes place to form the furan 109 from 2-(l-phenylethenyl)phe-nol[129]. Benzofuran formation by this method has been utilized in the synthesis of aklavinione (110)[130]. 

The intramolecular reaction oF allcenes with various O and N functional groups offers useful synthetic methods for heterocycles[13,14,166]. The reaction of unsaturated carboxylic acids affords lactones by either exo- or endo-cyclization depending on the positions of the double bond. The reaction of sodium salts of the 3-alkenoic acid 143 and 4-alkenoic acid 144 with Li2PdCl4 affords mostly five-membcrcd lactones in 30-40% yields[167]. Both 5-hexe-noic acid (145) and 4-hexenoic acid (146) are converted to five- or six-mem-bered lactones depending on the solvents and bases[168]. Conjugated 2,4-pentadienoic acid (147) is cyclized with Li2PdCl4 to give 2-pyrone (148) in water[i69]. 

Unlike the intermolecular reaction, the intramolecular aminopalladation proceeds more easily[13,14,166], Methylindole (164) is obtained by the intramolecular exo amination of 2-allylaniline (163). If there is another olefinic bond in the same molecule, the aminopalladation product 165 undergoes intramolecular alkene insertion to give the tricyclic compound 166[178]. 2,2-Dimethyl-l,2-dihydroquinoline (168) is obtained by endo cyclization of 2-(3,3-dimethyiallyl)aniline (167). The oxidative amination proceeds smoothly... 

The cyclization of the homologous epoxide 36 under acidic conditions was also investigated (Table 9.5) [110]. As would be expected, compound 36a reacted by a 6-exo cyclization to give tetrahydropyran 38a (Entry 1). The a, 3-unsaturated hydroxy epoxide 36b gave a 1 3.5 mixture of oxepane 37b and tetrahydropyran 38b (Entry 2). Subjection of 36c and 36d, which both contain more electron-rich 71-systems, to the reaction conditions resulted in preferential 7-endo cyclization to give 37c and 37d, thus confirming the powerful regiodirecting effect of the vinyl moiety (Entries 3 and 4). 

When free radicals are added to 1,5- or 1,6-dienes, the initially formed radical (9) can add intramolecularly to the other bond, leading to a cyclic product (10). When the radical is generated from an precursor that gives vinyl radical 11, however, cyclization leads to 12, which is in equilibrium with cyclopropylcarbinyl radical 13 via a 5-exo-trig reaction. A 6-endo-trig reaction leads to 14, but unless there are perturbing substituent effects, however, cyclopropanation should be the major process. 

A radical cyclization of a 2-chloroacyl enamine 157 was used to synthesize 2-substituted pyroglutamates 160. Usually, the radical 158 undergoes an initial 5-endo cyclization (path a) and the resulting intermediate 159 attacked electrophiles like methyl acrylate to give the pyroglutamate 160. Unexpectedly, the reaction with methyl methacrylate took another course and a seven-membered... 

Entry 11 involves generation and cyclization of an alkoxymethyl radical from a selenide. The cyclization mode is the anticipated 5-exo with a cis ring juncture. This is a case in which the electronic characteristics of the radical are not particularly favorable (ERG oxygen in the radical), but cyclization nevertheless proceeds readily. The reaction in Entry 12 was used to prepare a precursor of epibatidine. Entry 13 shows a 6-endo cyclization that is favored by steric factors. The 6-endo cyclization is also favored with a tetrahydropyranyloxy substituent in place of the ester, indicating that the electronic effect is not important. Entries 14 to 16 involve acyl radicals generated from selenides. The preferred 6-endo cyclization in Entry 15 is thought to be due to the preference for the less-substituted end of the double bond. Entry 17 is an example of a 5-exo-dig cyclization. 

Entries 18 to 19 pertain to cyclizations of electrophilic radicals generated by oxidations. Entry 18 is the prototype for cyclization of a number of more highly substituted systems. The reaction outcome is consistent with oxidation of the less-substituted enolic position followed by a 6-endo cyclization. The cyclized radical is then oxidized and deprotonated. In Entry 19, the vinyl radical formed by cyclization is reduced by hydrogen abstraction from the solvent ethanol. 

Kobayashi has found that scandium triflate, Sc(OTf)3,36 and lanthanide triflate, Ln(OTf)3, are stable and can be used as Lewis catalysts under aqueous conditions. Many other Lewis acids have also been reported to catalyze Diels-Alder reactions in aqueous media. For example, Engberts reported37 that the cyclization reaction in Eq. 12.7 in an aqueous solution containing 0.010 M Cu(N03)2 is 250,000 times faster than that in acetonitrile and about 1,000 times faster than that in water alone. Other salts, such as Co2+, Ni2+, and Zn2+, also catalyze the reaction, but not as effectively as Cu2+. However, water has no effect on the endo-exo selectivity for the Lewis-acid catalyzed reaction. 

The first type of process is characterized by cyclization reactions, which are found in a plethora of examples and hence can be considered as the flagship of the different classes being discussed in this section. In spite of the fact that this reaction type distinguishes a broad scope of subsections, the 5-exo-trig ring closure can be regarded as the most frequent and productive one. Furthermore, 6-endo and 6-... 

A modified Pictet-Spengler reaction has been applied to the synthesis of thiazolo-quinolines 58 <06T3228>. Condensation of anilines 53 with aryl aldehydes 54 followed by endo cyclization results in the formation of thiazoloquinolines 58 under a variety of traditional Pictet-Spengler protocols such as 2% trifluoroacetic acid in dichloromethane. 

Malonic acid allylic esters undergo intramolecular cyclization reaction under solid-liquid phase transfer catalytic conditions in the presence of Aliquat 336, potassium carbonate, and iodine (Eq. 60) [84]. Application of microwave irradiation to this procedure enabled 2-3-fold reduction in the reaction time compared with conventional conditions. It was found that use of microwaves affected the exo/endo diastereoi-somers ratio - a linear correlation between microwave power and exo isomer concentration was observed [85]. 

Barluenga et al. developed a novel exo-endo-cyclization of a,codiynes by use of bis(pyridyl) iodonium(I)-tetrafluoroborate (IPy2BF4) as catalyst.1171 The reaction follows a cationic-cationic pathway (scheme 6). First the electrophilic iodo ion reacts with the triple bond of 26 to give the relative stable vinyl cation 28. Ring closure leads to a seven-... 

Figure 2. Theozymes for hydroxyepoxide cyclizations. Antibody-catalyzed cyclization reactions are shown schematically in the box. Antibodies 26D9 and 5C8 were raised against haptens 4 and 5, respectively, (a) Theozymes (bold) complexed to the 6-endo cyclization transition state model.

An example of a 6-endo cyclization of an alcohol onto an alkene radical cation/phosphate anion pair has also been described (Scheme 22). In order to bring about fragmentation of the primary alkyl phosphate bond in this reaction it was necessary to work in a 1 1 mixture of benzene and acetonitrile [139,140],... 

All these reactions are examples of oxidative cyclocarbonylation-alkoxy-carbonylation. However, the Pdh/KI catalytic system turned out to be a very efficient catalyst also for promoting cyclization-alkoxycarbonylation processes. In fact, optimal conditions were found for selectively converting 4-yn-l-ols into tetrahydrofuran derivatives (Eq. 41) [107] through 5-exo-dig cyclization followed by alkoxycarbonylation (Scheme 19, path a). This kind of process was not possible for the propynyl, 3-yn-l-ol, and 2-ethynylaniline substrates, seen before, for stereoelectronic reasons [302], With the latter substrates, the endo cyclization mode (Scheme 19, path b), although in principle stereo electronically allowed, was not observed. 

One dramatic feature of antibody catalysts is their ability to reroute reaction pathways, thereby achieving disfavored chemical transformations instead of favored low-energy chemical processes. An archetypal example is the antibody-catalyzed disfavored 6-endo-intramolecular cyclization reaction of trawr-epoxyalcohol... 

Scheme 19)." Homoallyloxysilanes gave a mixture of five- and six-membered rings, but the intermediate silyl radical underwent predominantly 6-endo cyclization. Pentenyloxysilane gave the 1-endo product only. The stereochemistry of these reactions was found to be determined by steric effects, even in the presence of chiral thiol catalysts. The structures of the radical intermediates were studied by EPR. 

Extensive mechanistic investigation of the ring expansion 33 —> 34 was performed in order to differentiate between a ring-opening reaction to give a silyl radical 39 (path a), followed by the 6-endo cyclization, or a pentavalent silicon transition state 40 (path b). It was clearly demonstrated that the ring expansion proceeds via a pentavalent silicon transition state (Scheme 6.10) [16]. 

Analogously to the carbocycle and oxycycle synthesis, cyclic amines can be obtained by the hydrosilylation of a suitable enyne, such as 46 (Reaction 7.54), which gave the six-membered ring via a 6-endo cyclization of the vinyl radical onto the C=N bond [63]. In another example, the isothiocyanide functionality of compounds 47 or 48 reacts with silane under radical conditions... 

Free-radical reaction of vinyl iodides having dienoate function in the presence of (TMS)3SiH and AIBN in refluxing benzene caused a tandem cyclization reaction to produce (4 - -1) and (4 - - 2) annulated compounds [94]. Reaction (7.83) shows the transformation resulted from a tandem 5-exo, 6-endo cyclization to give the isoindole skeleton where the stereogenic centres were highly controlled, whereas Reaction (7.84) proceeded via a tandem 6-exo, 5-exo cyclization to furnish a (4 -b 1) cycloadduct. 

Novel bridged spirolactones have been synthesized via tandem radical cycli-zations of enol ether radical. In Reaction (7.85) the first 5-exo spirocyclization is followed by a 6-endo cyclization to give the bridged derivative as a single diastereoisomer [96]. 

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