Trigly process

An example of an exo-trig process would be lactonization of a m-hydroxycarboxylic acid ... 

Let us focus attention on the unfavorable ring closures. Why, for example, should formation of a five-membered ring by an endo-trig process be difficult The answer is provided by a consideration of the trajectory of approach of the nucleophile." If Z is an electron-attracting conjugating group of the type necessary to activate the double bond to nucleophilic attack, the reaction would involve the LUMO of the conjugated system, a 7t ... 

The only reported example of such hydroaminations concerns the IH of a-(aminoalkyl)styrenes (5-Exo-Trig process) (Eq. 4.36) [134]. 

IH of allenic amines also occurs in the presence of silver salts. IH of a-allenic amines proceeds in good yields in the presence of AgBp4 and provides a useful method for 3-pyrrolines synthesis via Endo-Trig processes (Eq. 4.93) [314]. 

Although less efficient (TOP = 0.04 h ), similar IH ofofy- and 5-allenic amines in the presence of AgNOj give 2-alkenylpyrrolidines and 2-alkenylpiperidines, respectively (5 [or 6]-Exo-Trig processes) [315]. These reactions have been applied to the synthesis of ( )-pinidine [316] and -) R) coniine [317]. 

Cathodic reduction of Ai-(2-iodophenyl)-A -alkylcinnamides under deaerated conditions forms l-alkyl-3-benzylindolin-2-ones regioselectively (70-85%), presumably in a radical or anionic S-exo-trig process. The mechanism has been explored by the use of cyclic voltammetry, controlled-potential electrolysis (cpe), and deuterium labeling [116]. 

For the alkynyUiydroxylamines 274 smdied by Holmes (309,311), initial intramolecular 1,3-azaprotiocyclotransfer affords the N-oxides 275 via a 5- or a 6-exo-dig process [Baldwin s terminology (312)], which then tautomerize to the cyclic nitrones (276) (Scheme 1.57). The 1-exo-dig cyclization required for the formation of a seven-membered nitrone (277) by this approach from 278 was found to be disfavored with respect to the alternative reaction of hydroxylamine and alkene 5-exo-trig process) to afford a mixture of the alkynylpyiTolidines 279... 

The rules of Baldwin (55) for ring closure in trigonal systems (see p. 171 for an introduction) are the following 3- to 7-Exo-Trig processes (152-156) are all favored processes. 3- to 5-Endo-Trig (157-159) are disfavored but 6- and 7-Endo-Triq (160-161) are favored. The literature is replete with examples of 3- to 7-Exo-Trig for instance, lactonization of u-hydroxy-acids and esters are of this type, the formation of lactams from w-aminoacids and also the Dieckmann cyclization of diesters. 

In another experiment (56), the disfavored 5-Endo-Trig process (159) was placed in competition with the favored 5-Exo-Trig process (154). The hydroxy conjugated ester 172 upon treatment with a variety of bases closed efficiently and cleanly to the lactone 173 (5-Exo-Trig process) with no trace... 

A nitrogen analog of J72 was also studied (56). The amino-diester 176, upon release from its stable hydrochloride salt, rapidly closed at 25°C to the lactam 177 (100%) via the favored 5-Exo-Trig pathway. The disfavored 5-Endo-Trig process yielding the cyclic amino-diester 178 was not observed. On the other hand, it is known that primary amines undergo a 1,4-addition to a-substituted acrylic esters (179 -> 180) more rapidly than they are acylated to the a-substituted acrylamides (179 ->181). 

The reactions of cinnamic acid derivatives with hydrazine are also in accord (56) with the above findings. The hydrazide 182 cannot, even at 200°C, be converted into the pyrazolone 185 (5-Endo-Trig process). However, the ester... 

Scheme 10. Concuirent 5-exo-trig and 6-endo-trig process...

Whereas 5-endo-trig processes are unfavorable, 6-endo-trig cyclizations are allowed. For this reason the reaction conditions used for several well-known preparations of six-membered rings cannot be used to prepare the corresponding five-membered rings. For example, treatment of phenethylamines with aldehydes and acid yields tetrahydroisochinolines (Pictet-Spengler synthesis), but treatment of benzylamines under these conditions does not yield dihydroisoindoles (Scheme 9.6). 

The authors also suggested (87) a mechanism for this rearrangement in refluxing methanol. In alkaline solution the normal-type immonium species 208 closes to ajaconine (80) and not to 7a-hydroxyatisine (205) because the latter closure, being a disfavored 5-endo-trig process, is much slower... 

Several different radical methods are available for the synthesis of six-membered nitrogen heterocycles. A manganese(III) acetate promoted addition of amino malonate radical to an alkene has been utilized for the preparation of an intermediate in the synthesis of loracarbef [95JOC6176]. The intermediate tertiary radical obtained by the 6-exo-trig process is trapped intramolecularly by one of the ester groups of the malonate. 

According to Baldwin s rules [76JCS(CC)234 92MI1 93ACR476], the cyclization 1A — IB, as a 5-endo-trig process, is disallowed. But despite these rules, the transformation 1A — IB is rather fast. Thus, the rate constant of the monomolecular cyclization of iminoalcohol 1A (R1 = H R2 = Me R3 = Ph), for example, has been estimated as k > 0.06 s 1... 

A sugar-derived vinyl sulfone (92) was found to undergo a Michael-initiated ring closure (MIRC) process to build up a chiral polysubstituted oxolan system with high stereoselectivity, yielding the all-syn stereoisomer (93) (Scheme 25).61 The observed MIRC selectivity demonstrates that the 5-exo-trig process is strongly... 

The intramolecular iodocyclization of 3-penten-l-ols performed with iodine/sodium hydrogen carbonate in dry acetonitrile allows tetrahydrofurans to be obtained via a 5-endo-trig process. This method can result in obtaining 2,5-tram- or 2,5-m-tetrahydrofurans. depending on the geometry of the double bond127 - no. 

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