6-endo-trig cyclisation

A one-pot synthesis of dihydropyranols features the diastereoselective cyclisation of allylic alcohols formed by elimination of HNO2 from the Michael adduct between cA-hex-3-en-2,5-diones and P-nitroalkanols (Scheme 1) <04SL2618>. The Mn(III)-catalysed reaction of alkenes with (2-aryl-2-oxoethyl)malonates proceeds through a 6-endo-trig cyclisation involving the ketone function and leads to tetrasubstituted dihydropyrans 12 <04TL3373>. 

Endo-trig cyclisations are rare for organolithiums, but endo-dig cyclisations are in general more favourable, and 5-endo-dig anionic cyclisations do occur. One possible example is the... 

Normally, 5-endo-trig-cyclisations are disfavoured geometrically (Baldwin s rules), however formation of pyrrolidines does take place with tosylamide anion as nucleophile in a situation where 5-ejco-fef-attack at a trihalomethyl group is inhibited electrostatically. ... 

In another example, 5-endo-trig-cyclisation of a 2-(2-tosylaminoethyl)acrylate occurs with a phenyl ester, but 5-exo-trig with an ethyl ester the relative leaving abilities of groups from the 5-exo-trig-intermediate allows the 5-endo-trig-pathway to dominate (TsN > EtO but PhO > TsN ) rationalizes this dichotomy. 

It is worth noting that these (5-endo-trig) cyclisations also occur readily in simple aliphatic systems, giving dihydro-heterocycles. ... 

In one of the earliest reports on indole radicals, Sundberg (90JOC6028) outlined an intramolecular radical addition of a 3-indolyl radical onto an isolated double bond (for the synthesis of analogues of Iboga alkaloids) to yield 128a-c providing a rare example of an S-endo-trig cyclisation (Scheme 31). 

A detailed study of the halocyclisation of unsaturated benzyl sulfides has shown that tetrahydrothiopyran formation is favoured from alkenyl sulfides through 6-endo-trig and 6-exo-trig modes. However, for alkynyl sulfides only the 6-exo-dig cyclisation is predominant, leading to dihydrothiopyrans (95JOC6468). 

In 2003, Molander reported the synthesis of (+ )-isoschizandrin using the Sml2-mediated 8-endo-trig carbonyl-alkene cyclisation of ketone 71 (Scheme 7.30).69 The axial chirality of the biaryl system efficiently controls the central chirality of the product. The (Z)-alkene geometry is also vital to the stereochemical outcome and the presence of HMPA in the reaction mixture helps control the conformation of the transition state by increasing the steric demands of the alkoxysamarium substituent.69... 

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