Transannular cyclisations

Carbocyclization of a monoepiselenonium intermediate derived from a diene has been discussed earlier in this chapter (Scheme 8),33 as was the acid-catalysed transannular cyclisation of a bisalkyne (Scheme 9).41... 

In 2007, Molander demonstrated that 5-exo-transannular reductive carbonyl addition to an endo- or exocyclic alkene can be highly effective for the formation of bicyclic ring systems. For example, treatment of cyclooctenone 36 with Sml2 and HMPA gave bicyclic alcohol 37 in 70% yield (Scheme 5.28).56 Transannular cyclisations have even been extended to 11-membered carbo-cyclic starting materials and give bicyclic products in good yield. 

A sequential alkoxyl radical fragmentation-transannular radical cyclisation has been used in a new approach to the bicyclo-[5.3.0]decanone ring system,irradiation of the 8-decanol (125) in the presence of iodosylbenzene diacetate and iodine, for example, gave the substituted hydroazulenone (126) via the mono-cyclic radical (127). 

A new, stereospecific synthesis of (+)-isoretronecanol, by a transannular route, has been developed by Leonard et al. Dieckmann cyclisation of NN-bis-(y-ethoxycarbonylpropyl)benzylamine gave ethyl l-benzyl-5-oxo-l-azacyclo-octane-4-carboxylate (20), whose perchlorate was shown to possess a bicyclic structure. Hydrogenation of this perchlorate in ethanol, using palladised charcoal catalyst, afforded ethyl ( )-isoretronecanolate perchlorate (22) as sole product, presumably by stereospecific addition of hydrogen at the less hindered face of the intermediate debenzylated immonium ion (21). Reduction of the free base corresponding to (22), by means of lithium aluminium hydride, gave (+ )-isoretronecanol (23), the stereochemical purity of which was shown by g.l.c. analysis to be >98%. 

One interesting facet of the germacrane-type sesquiterpenoids is the conformation of the ten-membered ring. This aspect has previously been discussed in terms of transannular electronic effects (anomalous u.v. spectra) and transannular chemical reactions (Cope rearrangement and cyclisations to eudesmane and/or guaiane types). Recently, the power of two spectroscopic techniques has been brought to bear on this problem. The first of these is the use of the Nuclear Overhauser Effect (NOE) and the second is the A"-ray analysis of a suitable derivative. 

The 5 -perhydroazulene structure (524) is accessible by solvolysis of a la-mesylate (523)." The comparable reaction in the 5a-series requires solvolysis of a 1 -substituted steroid. In each case the migrating C jj-C o) bond has an onti-periplanar relationship to the leaving group. Related perhydroazulenes (526) are obtained by transannular cyclisation of the 5,10-seco-steroid (525). ... 

Titanocene-catalysed transannular cyclisation OF EPOXYGERMACROLIDES enantospecific synthesis of EUDESMANOLIDES... 

TITANOCENE-CATALYSED TRANSANNULAR CYCLISATION OF EPOXYGERMACROLIDES ENANTIOSPECIFIC SYNTHESIS OF EUDESMANOLIDES... 

These compounds have a distinct biogenetic origin than the other taxoids, resulting from a transannular cyclisation, which is different from that involved in the formation of normal taxanes (92). They are tricyclic systems with a ten membered ring sandwiched between two six membered rings. Isolates of this class from Taxus species are listed in Table 4. 

The group of Boger described the total synthesis of kopsinine, a member of the Aspidosperma alkaloids, using their landmark [4 + 2]/[3 + 2] cycloaddition cascade for the conversion of 44 to 45 (Scheme 16). An unusual Sml2-promoted transannular cyclisation of xanthate 46, formed the bicyclo[2,2,2]octane moiety and provided the highly compact core of the natural product 48 as a single diastereoisomer. Although 48 is the least stable diastereoisomer, its formation is consistent with a radical cyclisation mechanism followed by kinetic protonation of the samarium enolate 47 formed after a second electron transfer. 

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