Modular Access to meta-Substituted Benzenes via Mo-Catalyzed Intermolecular Deoxygenative Benzene Formation.

The substituted benzene derivatives are essential to organic synthesis, medicinal chemistry, and material science. However, the 1,3-di- and 1,3,5-trisubstituted benzenes are far less prevalent in small-molecule drugs than other substitution patterns, likely due to the lack of robust, efficient, and convenient synthetic methods. Here, we report a Mo-catalyzed intermolecular deoxygenative benzene-forming reaction of readily available ynones and allylic amines. A wide range of unsymmetric and unfunctionalized 1,3-di- and 1,3,5-trisubstituted benzenes were obtained in up to 88% yield by using a commercially available molybdenum catalyst. The synthetic potential of the method was further illustrated by synthetic transformations, a scale-up synthesis, and derivatization of bioactive molecules. Preliminary mechanistic studies suggested that this benzene-forming process might proceed through a Mo-catalyzed aza-Michael addition/[1,5]-hydride shift/cyclization/aromatization cascade. This strategy not only provided a facile, robust, and modular approach to various meta-substituted benzene derivatives but also demonstrated the potential of molybdenum catalysis in the challenging intermolecular deoxygenative cross-coupling reactions.

Molybdenum-Catalyzed Deoxygenative Cyclopropanation of 1,2-Dicarbonyl or Monocarbonyl Compounds.

The transition-metal-catalyzed cyclopropanation of alkenes by the decomposition of diazo compounds is a powerful and straightforward strategy to produce cyclopropanes, but is tempered by the potentially explosive nature of diazo substrates. Herein we report the Mo-catalyzed regiospecific deoxygenative cyclopropanation of readily available and bench-stable 1,2-dicarbonyl compounds, in which one of the two carbonyl groups acts as a carbene equivalent upon deoxygenation and engages in the subsequent cyclopropanation process. The use of a commercially available Mo catalyst afforded an array of valuable cyclopropanes with exclusive regioselectivity in up to 90 % yield. The synthetic utility of this method was further demonstrated by gram-scale syntheses, late-stage functionalization, and the cyclopropanation of a simple monocarbonyl compound. Preliminary mechanistic studies suggest that phosphine (or silane) acts as both a mild reductant and a good oxygen acceptor that efficiently regenerates the catalytically active Mo catalyst through reduction of the Mo-oxo complexes.

CT-Based Collision Prediction Software for External-Beam Radiation Therapy.

PURPOSE: Beam angle optimization is a critical issue for modern radiotherapy (RT) and is a challenging task, especially for large body sizes and noncoplanar designs. Noncoplanar RT techniques may have dosimetric advantages but increase the risk of mechanical collision. We propose a software solution to accurately predict colliding/noncolliding configurations for coplanar and noncoplanar beams. MATERIALS AND METHODS: Individualized software models for two different linear accelerators were built to simulate noncolliding gantry orientations for phantom/patient subjects. The sizes and shapes of the accelerators were delineated based on their manuals and on-site measurements. The external surfaces of the subjects were automatically contoured based on computed tomography (CT) simulations. An Alderson Radiation Therapy phantom was used to predict the accuracy of spatial collision prediction by the software. A gantry collision problem encountered by one patient during initial setup was also used to test the validity of the software. Results: In the comparison between the software estimates and on-site measurements, the noncoplanar collision angles were all predicted within a 5-degree difference in gantry position. The confusion matrix was calculated for each of the two empty accelerator models, and the accuracies were 98.7% and 97.3%. The true positive rates were 97.7% and 96.9%, while the true negative rates were 99.8% and 97.9%, respectively. For the phantom study, the collision angles were predicted within a 5-degree difference. The software successfully predicted the collision problem encountered by the breast cancer patient in the initial setup position and generated shifted coordinates that were validated to correspond to a noncolliding geometry. CONCLUSION: The developed software effectively and accurately predicted collisions for accelerator-only, phantom, and patient setups. This software may help prevent collisions and expand the range of spatially applicable beam angles.