The initial step in the mechanism-based inactivation of ribonucleotide reductases by 2’-chloro-2’-deoxynucleotides is abstraction of H3’ by a proximal free radical on the enzyme. The C3’ radical is postulated to undergo spontaneous loss of chloride, and the resulting cationic radical loses a proton to give a 3’-keto intermediate. Successive beta-eliminations produce a Michael acceptor which causes inactivation. This hypothesis would predict rapid loss of mesylate or tosylate anions from C2’, but sluggish loss of azide or thiomethoxide. in contrast, loss of azido and methylthio radicals from C2’ should occur readily whereas homolysis to give (methyl or tolylsulfonyl)oxy and fluoro radicals should be energetically prohibitive. Protected 3’-O-(phenoxythiocarbonyl)-2’-substitute nucleosides were treated with tributylstannane/AIBN or triphenylsilane/dibenzoyl peroxide in refluxing toluene. The 2’-O-(mesyl and tosyl) and 2’-fluoro compounds underwent direct radical-mediated hydrogenolysis of the thionocarbonate group to give 3’-deoxy-2’-substituted products, whereas 2’-(azido, bromo, chloro, iodo, and methylthio)-3’-thionocarbonates gave 2’,3’-didehydro-2’,3’-dideoxy derivatives via loss of 2’-substituents from an incipient C3’ radical.