There has been expanding interest in exploring porous metal oxides as a confining environment for organic molecules resulting in altered chemical and physical properties including chemical transformations. In this paper, we examine the pyrolysis behavior of phenethyl phenyl ether (PPE) confined in mesoporous silica by covalent tethers to the pore walls as a function of tether density and the presence of cotethered surface spacer molecules of varying structure (biphenyl, naphthyl, octyl, and hexadecyl). The PPE pyrolysis product selectivity, which is determined by two competitive free-radical pathways cycling through the two aliphatic radical intermediates (PhCH center dot CH(2)OPh and PhCH(2)CH center dot OPh), is shown to be significantly different from that measured in the liquid phase as well as for PPE tethered to the exterior surface of nonporous silica nanoparticles. Tailoring the pore surface with spacer molecules further alters the selectivity such that the PPE reaction channel involving a molecular rearrangement (O-C phenyl shift in PhCH(2)CH center dot OPh), which accounts for 2596 of the products in the liquid phase, can be virtually eliminated under pore confinement conditions. The origin of this change in selectivity is discussed in the context of steric constraints on the rearrangement path inside the pores, surface and pore confinement effects, pore surface curvature, and hydrogen bonding of PPE with residual surface silanols supplemented by nitrogen physisorption data and molecular dynamics simulations.