5-Exo-trig closure

Application of similar considerations to homolytic ring closures indicates that a 5-exo-trig closure will be preferred to a 6-endo-trig mode (Scheme 6) (80CC482). For cationic closures the 5-endo-trig mode is unknown in contrast to the well-established 6-endo-trig closure (Scheme 7). 

Intermolecular carbometallations are typically accomplished with organolithiums however, dia-stereocontrolled intramolecular carbometallation can be attained with appropriate Grignard reagents, as exemplified in Scheme 88, the suprafacial and 5-exo-trig closure of ( )-6-bromo-3-methyl-1 -trimethylsi-lyl-1-hexene (267) to fraru-l-methyl-2-(trimethylsilyl)methylcyclopentane (268).203... 

It should be noted that the radical cyclization proceeds to yield a five-membered ring and not a six-membered one. This is predicted by the Baldwin rules for ring-closure and is classified as a 5-exo-trig closure ". LiAlH4 has also been used to generate the cyclopropyl radical which also underwent a 5-exo-trig ring-closure. ... 

An experimental and computational study describing a cascade transformation that breaks all three C-C bonds in a polarized alkyne moiety has been reported (Scheme 5)." Facile intermolecular Michael addition is followed by the relatively slow intramolecular steps. The slowest step corresponds to the 5-exo trig closure at the carbonyl-substituted alkene. This process is facilitated by the coupling of the intramolecular Michael addition with a concerted proton transfer along a resonance-assisted hydrogen bond path, which avoids the formation of an unfavourable zwitterionic intermediate. 

With 6-alkenoic acids the intermediate radical partially cyclizes to a cyclopentyl-methyl radical in a 5-exo-trig cycHzation [139] (Eq. 6) [138 a, 140] (see also chap. 6). To prevent double bond migration with enoic acids the electrolyte has to be hindered to become alkaline by using a mercury cathode. Z-4-Enoic acids partially isomerize to -configurated products. Results from methyl and deuterium labelled carboxylic acids support an isomerization by way of a reversible ring closure to cyclopropyl-carbinyl radicals. The double bonds of Z-N-enoic acids with N > 5 fully retain their configuration [140]. 

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-... 

Electrolysis of b-al Ionic ketone 61 at a controlled cathode potential of-2.43 V (versus Ag/AgI) in anhydrous DMF using tetraethylammonium p-toluenesulfonate as co-electrolyte provides the derived ketyl radical that undergoes a 5-exo-trig selective ring closure, presumably via transition structure 62 (Scheme 11.19). The cyclization product is further reduced and subsequently protonated to afford traus-configurcd cyclopentanol 63 as single diastereomer in a total yield of 55% [80]. 

The principle side reaction corresponds to reduction of the carbonyl without cyclization. For example, reduction of 6-methylhept-6-en-2-one (113) leads to a 12% yield of alcohol 114 no cyclized adduct 115 is produced. Were the intermediate to behave precisely like the monoradical, one would have anticipated that the presence of the methyl group on the alkene would have slowed the rate of 5-exo-trig cyclization to a point where closure to form 115, the product of a 6-endo-trig cyclization, would have dominated it did not. 

Unfortunately, the scope of the process appears to be limited by the need to form a five-membered ring in the second ring closure event [64]. For example, reduction of 220 affords 221 and 222, each the result of a 5-exo-trig cyclization (Table 10). Apparently, the rate of 6-exo-trig cyclization of the putative... 

The ethoxycarbocation intermediate (363) produced by the action of acid on the cyclobutenedione monoacetal (362) has been found to react with bis(trimethylsilyl)-acetylene to afford a 2-methylenecyclopent-4-ene-l,3-dione derivative (365). The authors426 proposed that the rearrangement results from an unprecedented cationic 1,2-silyl migration on the alkynylsilane, subsequent ring expansion via a vinyl cation intermediate (364), and re-closure by intramolecular addition of an acyl cation to a silylallene in a 5-exo-trig mode (see Scheme 90). 

A stereospecific, Pd-catalysed, 5-exo-Trig ring closure reaction of 328 has been reported442,443. 

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