Radicals ketyl cyclisations

Evidence of both types of potential intermediate in reduction by Sml2, the alkyl radical and the ketyl radical 27, has been provided by radical cyclisation reactions. Mechanism 4, which involves an Sjj2 substitution, has been eliminated because optically active halides are completely racemised. The rate of addition of alkyl radicals to ketones is very slow (<102 dm3 mol-1 s-1) the resulting alkoxy radicals (26) are very reactive and could not... 

Additional support for an alternative alkene first mechanism in these cyclisations came from the successful cyclisation of cyclopropyl ketone 26 with no observance of fragmentation products (Scheme 5.21).43 This suggests that a ketyl radical anion is not formed during the cyclisation and that reduction of the alkene leads to product formation. 

The reaction mechanism involved the cyclisation of ketyl radical anion 3 on to the methylenecyclopropane moiety in a 5-exo-trig manner. Ring opening of cyclopropane intermediate 4 gave rise to the cyclohexyl radical 5, which then cyclised in a 5-exo-dig fashion to form the second ring (Scheme 6.2).5,6... 

Radical cyclisation-anionic sequences, in which the radical cyclisation involves the addition of a ketyl radical anion to an alkene, are also possible. For example, carbonyl-alkene cyclisation of unsaturated ketone 19 and quenching of the resultant organosamarium with electrophiles allow access to an impressive range of cyclopentanol products (Scheme 6.7).12... 

Chelation-controlled ketyl radical cyclisations can also be employed in radical-anionic sequences. For example, treatment of ketolactone 20 with Sml2 in the presence of acetone gives adduct 21 with good diastereocontrol (Scheme 6.8).13... 

Enholm reported radical-anionic sequences involving ketyl radical cyclisa-tions that culminate in intermolecular aldol reactions treatment of aldehyde 24 and cyclohexane carboxaldehyde with Sml2 triggers a radical cyclisation-intermolecular aldol sequence to give 25 in good yield (Scheme 6.10).15... 

Pestalotiopsin A and 6-epitaedolidol are structurally related caryophyllene-type sesquiterpenes. In 2003, Procter reported the use of a Sml2-mediated 4-exo-trig carbonyl-alkene cyclisation to construct the core of pestalotiopsin A.57 Treatment of cyclisation substrate 33 with Sml2 in THF, MeOH and 2,2,2-trifluoroethanol gave cyclobutanol products 34 and 35 in good yield and with moderate diastereoselectivity. The major diastereoisomer is believed to arise from a cyclisation in which coordination to the silyl ether group directs addition of the ketyl radical anion to the alkene (Scheme 7.17).57... 

Previously, tin-ketyl radicals have been added to alkenes only in an intramolecular fashion. [9] In recent publications, however, pinacols and amino alcohols have been prepared by cyclisation of dicarbonyl compounds [10] or keto-oximes [11] with tributyltin hydride. Cyclisation of 1,5-ketoaldehydes 1 and 1,5-dialdehydes with tributyltin hydride yields cw-diols 2 with excellent stereoselectivities, whereas the keto-oxime 4 with four benzyloxy-substituents affords a 58 42 cis trans) mixture. The tran -product was transformed in two more steps to the potent glycosidase inhibitor 1-deoxynojirimycin (6). [lib] The reversibility of both the addition of the tributyltin-radical to the carbonyl group and the intramolecular radical C-C bond formation is believed to be responsible for the high selectivity in the formation of 2. In the cyclisation of 1,5-pentanedial the unhydrolyzed coupling product 3 could be isolated, therefore providing evidence for a new mechanistic variant of the pinacol reaction, in which only 1.2 equivalent of the reducing agent are necessary. 

Building on their earlier research into S-endo cyclisations of Sml2-generated ketyl-type radicals, Molander and co-workers [107,108] developed this process as a key step in the syntheses of several naturally occurring lignans of the dibenzocyclooctadiene type. For example, they prepared the biaryl-chromium tricarbonyl complex 128 containing orffio-formyl and butenolide... 

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