The synthesis of the C5‘ tert-butyl ketone of thymidine 1a and 2‘-deoxyguanosine 2 is achieved by reaction of 5‘-C-cyano derivatives with tert-butyl lithium followed by acid hydrolysis. The 5‘R configuration is assigned by X-ray crystal structure determination of an opportunely protected derivative of 1a. The (5‘S)-isomers of both nucleosides are not stable, and a complete decomposition occurs in the reaction medium. The photochemistry of 1a and 2 effectively produced the thymidin-5‘-yl radical and the 2‘-deoxyguanosin-5‘-yl radical, respectively. In the thymidine system, the C5‘ radical is fully quenched in the presence of a physiological concentration of thiols. In the 2‘-deoxyguanosine system, the C5‘ radical undergoes intramolecular attack onto the C8−N7 double bond of guanine leading ultimately to the 5‘,8-cyclo-2‘-deoxyguanosine derivative. The cyclization of the 2‘-deoxyguanosin-5‘-yl radical occurs with a rate constant of ca. 1 × 106 s-1 and is highly stereoselective affording only the (5‘S)-diastereomer.

O-tert-Butyldimethylsilylimidazolyl aminals are N,Oacetals that form readily from aldehydes, and although they function as aldehyde stabilizing and protecting groups under various conditions, we report here that they react with organolithium reagents similarly to the parent aldehydes. The mechanism involves the intermediate formation of a 2-imidazolyl anion as is exemplified by the isolation of 2-TBDMS-imidazole. Substitution of the imidazolyl moiety at the 2-position renders these aldehyde derivatives stable to organolithium reagents, thus allowing for the tuning of their reactivity.

Reactions of organo-metal compounds Reactions of organo-metal compounds O 0350Tuning the Reactivity of O-tert-Butyldimethylsilylimidazolyl Aminals Towards Organolithium Reagents. -The N,O-silylimidazoles aminals (II) react with organolithium reagents similarly to the parent aldehyde yielding secondary alcohols (IV). Since their mechanism of formation involves a silyl migration from the oxygen to the 2-position of the imidazole it is expected, that 2-substituted imidazoles are unreactive against organolithiums. Thus, the N,O-acetals (VII) are prepared and found to be stable at -78°C in the presence of organolithium reagents. -(GIMISIS*, T.; ARSENYAN, P.; GEORGANAKIS, D.; LEONDIADIS, L.; Synlett 2003, 10, 1451-1454; Lab. Org.