Intermolecular C(sp3)–H insertions of β-carbonyl ester dirhodium-carbenes are extremely rare. Toward developing efficient reactions of these carbenes, a model for their insertion into C(sp3)–H bonds is described using density functional theory (DFT) calculations. In this study, the relevant electronic and steric components of β-carbonyl ester dirhodium-carbenes that affect intermolecular C(sp3)–H activation energies are explored, parametrized, and used to construct an intuitive model for predicting propensity for C–H insertion. The resulting insights from the theoretical investigation are actualized through experiments to establish reactivity trends for these species and reaction discovery. On the basis of these integrated computational and experimental efforts, examples of intermolecular C(sp3)–H insertions featuring secondary α-diazo-β-amide esters are reported. The resulting carbenes feature an intramolecular 1,6-hydrogen bond that affords increased stability and enhanced reactivity for C(sp3)–H insertion as compared to other β-carbonyl ester dirhodium-carbenes. The reactivity of these carbenes is also highlighted through (1) an example of a cyclopropanation reaction and (2) the use of a chiral dirhodium catalyst system.