Ring closure reactions were investigated in a combined computational (density functional theory) and experimental study, to uncover the origin of diastereoselection in 5-exo-trig cyclizations of methyl and tert-butyl-substituted 4-penten-1-oxyl radicals. Selectivity data were calculated on the basis of transition state theory, the Curtin-Hammett principle, and Maxwell-Boltzmann statistics, to provide an excellent correlation between computed and experimental cis-trans ratios. The data show that the 2,3-trans-, 2,4-cis-, and 2,5-trans-diastereoselection exerted by CH3 and C(CH3)3 groups increases along substituent positions 1 < 2 < 3, with the effect of tert-butyl substituents being more pronounced. Theory states that the favored mode of cyclization proceeds via intermediates that are characterized by an offset of atoms C2 and C3 into opposite directions from the plane of O1 (radical center)/C5 (olefinic C)/C4 (allylic C). This arrangement allows alkyl substituents and the =CH2 entity to adopt positions that are associated with the fewest and least severe synclinal and synperiplanar interactions. A transition structure notation is proposed based on conformational characteristics of the heterocycle, the intermediates structurally resemble the closest, i.e. tetrahydrofuran. The new transition state model serves as an alternative to cyclohexane-based guidelines and adequately addresses hitherto unsettled instances properly, such as the lack in diastereoselectivity observed in the 1-phenyl-4-penten-1 -oxyl radical 5-exo-trig ring closure.