Deconvoluting Nonlinear Catalyst-Substrate Effects in the Intramolecular Dirhodium-Catalyzed C-H Insertion of Donor/Donor Carbenes Using Data Science Tools.

Interactions between catalysts and substrates can be highly complex and dynamic, often complicating the development of models to either predict or understand such processes. A dirhodium(II)-catalyzed C-H insertion of donor/donor carbenes into 2-alkoxybenzophenone substrates to form benzodihydrofurans was selected as a model system to explore nonlinear methods to achieve a mechanistic understanding. We found that the application of traditional methods of multivariate linear regression (MLR) correlating DFT-derived descriptors of catalysts and substrates leads to poorly performing models. This inspired the introduction of nonlinear descriptor relationships into modeling by applying the sure independence screening and sparsifying operator (SISSO) algorithm. Based on SISSO-generated descriptors, a high-performing MLR model was identified that predicts external validation points well. Mechanistic interpretation was aided by the deconstruction of feature relationships using chemical space maps, decision trees, and linear descriptors. Substrates were found to have a strong dependence on steric effects for determining their innate cyclization selectivity preferences. Catalyst reactive site features can then be matched to product features to tune or override the resultant diastereoselectivity within the substrate-dictated ranges. This case study presents a method for understanding complex interactions often encountered in catalysis by using nonlinear modeling methods and linear deconvolution by pattern recognition.

Monte Carlo evaluation of occupational exposure during uterine artery embolization.

PURPOSE: Uterine fibroids affect women mainly of childbearing age, an alternative for the treatment of these fibroids is uterine artery embolization (UAE), a minimally invasive procedure which uses fluoroscopy, providing radiation doses often high, due to the fact that professionals remain in the room throughout the procedure. In this work, equivalent and effective doses were evaluated for the main physician, for the assistant and for the patient during the UAE procedure. METHODS: Doses were calculated using computer simulation with the Monte Carlo Method, and virtual anthropomorphic phantoms, in a typical scenario of interventional radiology with field sizes of 20 × 20, 25 × 25 and 32 × 32 cm2, tube voltages of 70, 80, 90 and 100 kV, and projections of LAO45, RAO45 and PA. RESULTS: The results showed that the highest doses received by the professionals were for the LAO45 projection with 32 × 32 cm2 field size and 100 kV tube voltage, which is in accordance with the existing literature. The highest equivalent doses, without the protective equipment, were in the eyes, skin, breast and stomach for the main physician, and for the assistant they were in the eyes, breast, thyroid and skin. When she used the protective equipment, the highest equivalent doses for the main physician were on the skin, brain, bone marrow and bone surface, and for the assistant they were on the skin, brain, red bone marrow and bone surface. CONCLUSIONS: Effective doses increased up to 3186% for the main physician, and 2462% for the assistant, without protective equipment, thus showing their importance.

Transition Metal Catalyzed Insertion Reactions with Donor/Donor Carbenes.

Donor/donor carbenes are relatively new in the field of carbene chemistry; although applications in C-H and X-H insertion reactions are few in number, they demonstrate exquisite chemo- and stereo-selectivity. Recent reports have shown that C-H, N-H, B-H, O-H, S-H, Si-H, Ge-H, Sn-H and P-H insertion reactions are feasible with a variety of transition metal catalysts, both inter- and intramolecularly. Furthermore, high degrees of diastereo- and enantioselectivity have been observed in several cases. Methods typically involve the formation of a diazo-based carbene precursor, but procedures using diazo-free metal carbenes have been developed with significant success. This Minireview covers transition-metal catalyzed insertion reactions with donor/donor and donor carbenes, providing context for future developments in this emerging field.

Acyclic Stereocontrol in the Additions of Nucleophilic Alkenes to α-Chiral N-Sulfonyl Imines.

Diastereoselective Lewis acid-mediated additions of nucleophilic alkenes to N-sulfonyl imines are reported. The canonical polar Felkin-Anh model describing additions to carbonyls does not adequately describe analogous additions to N-sulfonyl imines. Herein, we describe the development of conditions to produce both syn and anti products with high diastereoselectivity and good yields. A stereoelectronic model consistent with experimental outcomes is also proposed.

Enantioselective Synthesis of Indolines, Benzodihydrothiophenes, and Indanes by C-H Insertion of Donor/Donor Carbenes.

We employ a single catalyst/oxidant system to enable the asymmetric syntheses of indolines, benzodihydrothiophenes, and indanes by C-H insertion of donor/donor carbenes. This methodology enables the rapid construction of densely substituted five-membered rings that form the core of many drug targets and natural products. Furthermore, oxidation of hydrazones to the corresponding diazo compounds proceeds in situ, enabling a relatively facile one- or two-pot protocol in which isolation of potentially explosive diazo alkanes is avoided. Regioselectivity studies were performed to determine the impact of sterics and electronics in donor/donor metal carbene C-H insertions to form indolines. This methodology was applied to a variety of substrates in high yield, diastereomeric, and enantiomeric ratios and to the synthesis of a patented indane estrogen receptor agonist with anti-cancer activity.