Ketyl Radical Anions from Carbonyl Groups

3 Ketyl Radical Anions from Carbonyl Groups 

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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... 

Attempts to extend this work to the keto-oxime substrate 54 derived from D-glucosamine with an JV-phthalimido group resulted in the formation of a completely different product (Scheme 40). In this case, cyclization was initiated by reduction of the phthalimido carbonyl group to its corresponding ketyl radical anion followed by cyclization onto the ketone, providing an a-hydroxylactam 55 which was proposed to be a potentially useful scaffold for diversity-oriented synthesis. 

Following the observation that only the carbonyl group was electrochemically reduced under the experimental conditions used, a radical formed via protonation of the ketyl radical anion resulting from a one-electron transfer was suggested as the key intermediate responsible for the coupling (Scheme 26). 

When saturated steroidal ketones are reduced in ammonia, an alcohol is usually present to act as a proton donor and high yields of steroidal alcohols are obtained. Under these conditions, reduction probably proceeds by protonation of the radical-anion (or ketyl) (61), which results from a one electron addition to the carbonyl group, followed by addition of a second electron and proton. Barton has proposed that reduction proceeds via protonation of the dianion (62) arising from addition of two electrons to the carbonyl group. This proposal implies that the ketyl (61) undergoes addition of a second electron in preference to undergoing protonation by the... 

A mechanistic scheme for the titanium-mediated coupling of two carbonyl groups involves an initial one-electron transfer from titanium metal to the aldehyde or ketone carbonyl group to produce radical anions (ketyl species), which then dimerize to a Ti-pinacolate. Hydrolysis of the pinacolate generates the vicinal diol. 

In such a structure there must be considerable resonance interaction between the carbonyl group and the electron associated with the ionized OH adduct. Under these conditions, therefore, an absorption spectrum similar to the normal ketyl anion would not be unlikely. If then, the absorption at 4400 A. at high pH includes a component caused by the species arising from oxidative attack by OH or O" radicals as well as that caused by the ketyl anion, it is not surprising that adding N20 has little effect, even if the conversion of e aq to OH was complete during the pulse. 

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