We report the first example of ambimodal (2 + 1)/(4 + 1) pseudopericyclic transition states (TSs) in reactions between dihalocarbenes and olefins. Quasi-classical molecular dynamics simulations of the model reaction between dibromocarbene and 1,2-bis(methylene)cycloheptane reveal a single ambimodal TS that bifurcates to the experimentally observed (2 + 1) and (4 + 1) products. Intrinsic bond orbital (IBO) and principal interacting orbital (PIO) analyses attribute this ambimodality to the amphiphilicity of dibromocarbene: its empty p-type orbital engages the diene HOMO, while its sigma-lone pair interacts with both the C2 and C4 lobes of the diene LUMO. The resulting ambimodal transition structure displays a large disparity in competing bond lengths-an outlier relative to established correlations between bond length differences and ambimodal selectivity. Entropic path sampling reveals a pronounced entropic trap along the (2 + 1) pathway, giving rise to a post-transition-state dynamical intermediate that promotes extensive roaming rather than immediate product formation. This dynamic window allows the weaker (4 + 1) interaction to develop and compete, thereby enabling ambimodality despite the substantial bond length difference. An analogous ambimodal (2 + 1)/(4 + 1) cycloaddition is identified between nucleophilic dimethoxycarbene and alkenyl aldehyde relevant to natural product synthesis, underscoring the generality and synthetic utility of this manifold. Together, these findings reveal how structure, orbital interactions, and post-transition-state dynamics cooperatively govern ambimodal selectivity in this previously unrecognized carbene reaction manifold and provide a foundation for developing new strategies to tune reaction selectivity.

Electrophilic nitration is a fundamental transformation in organic synthesis; however, traditional mineral acid-based methods suffer from harsh conditions and limited substrate scope, motivating the development of organic electrophilic nitrating reagents. Here, we present a comprehensive computational investigation of the nitronium cation donating ability (NC+DA) of more than 50 reagents, including alkyl nitrates, nitric anhydrides, N-nitropyridinium salts, N-nitropyrazoles, N-nitroamides, pyridazinone derivatives, and other heterocyclic systems. The results enable the establishment a systematic NC+DA scale and reveal detailed structure-reactivity relationships influenced by electronic and steric factors. Guided by this scale, several potential N-nitroamide-type reagents with lower NC+DA values than existing nitroamides were designed. This work provides a quantitative framework for understanding and predicting the reactivity of organic electrophilic nitrating reagents and offers a rational basis for the design of next-generation electrophilic nitrating reagents for synthetic applications.

Herein we present a concise synthesis of the flagship member of limonoids, deoxylimonin, by a bioinspired skeletal reorganization approach. Key features of this synthesis include a stereoconvergent radical polyene cyclization to assemble the 6/6/6 tricyclic system, an oxime-directed Baldwin-Sanford oxidation to hydroxylate the unactivated C7-H, a titanium-mediated intermolecular aldol reaction to introduce the 3-furanyl lactone moiety and two contiguous stereogenic centers, and a biomimetic transesterification/oxa-Michael addition cascade to install the tetrahydrofuran-delta-lactone-fused motif. This work emphasizes the power of bioinspired skeletal reorganization in the simplified synthesis of complex terpenoids.