Additional mechanistic insights were gained by examining the photoisomerization of 9a to 10a (Scheme 3). Analysis of the reaction by H NMR (CD3CN, 0.03 M) revealed a rapid E-to-Z geometric isomerization of the exocyclic alkene. In this case, a 1.5:1.0 ratio of (E)-9a and (Z)-9a was reached after 0.5 h, and this photostationary state persisted as 10a accumulated over 4 h (4:1 d.r., 42% yield). This result is consistent with a radical-like cyclization that occurs from the triplet hypersurface. Further evidence for this mechanism was gained by DFT calculations, which indicated that an asynchronous reaction pathway from and TS-2. Gratifyingly, DDG ‡ was estimated as 0.7 kcal/mol in THF at 35 °C, an energetic difference that is within reasonable agreement with the 9:1 ratio of 10a and C3-epi-10a observed under these conditions. The sterically-controlled positioning of substituents at C3 in TS-2 was recognized as an important aspect of our working mechanistic hypothesis. This model suggests that the larger of the two groups in 9 (i.e. X vs. Y) will preferentially locate to the b-face of 12. To test this possibility, we prepared a library of photosubstrates 9 with different groups at C3 and evaluated the impact of these changes on the stereoselective formation of 12 (Scheme 4). As predicted, we observed that protecting the C3 alcohol as a silyl ether reduced the d.r. in 12b (X = Me, Y = OTBS, 30% yield) to 2:1. In contrast, deletion of the C3 alcohol increased the d.r. to >20:1 in 12c (X = Me, Y = H, 71% yield). Alternatively, replacing the methyl group with a hydrogen atom diminished the stereoselectivity as evidenced by the 1.2:1 d.r. observed for 12d (X = OH, Y = H, 44% yield). As suggested by these results, increasing the steric size of the alkyl group at C3 (i.e. X) improved the diastereoselectivity. Thus, structures 12e (X = CF3, Y = OH), 12f (X = c-propyl, Y = OH), and 12g (X = Ph, Y = OH) were produced in >20:1 d.r. and isolated in >70% yield. Together, these results illustrate that the stereochemical outcome of this photoinitiated cycloisomerization cascade can be guided by sterically differentiated substituents at C3. This feature is expected to facilitate asymmetric entry to ophiobolin variants in future iterations.