Abstract1,5-Diarylsubstituted 1,2,3-triazoles are formed in high yield from aryl azides and terminal alkynes in DMSO in the presence of catalytic tetraalkyl ammonium hydroxide. The reaction is experimentally simple, does not require a transition-metal catalyst, and is not sensitive to atmospheric oxygen and moisture.The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) is a reliable means for the synthesis of 1,4-disubstituted-1H-1,2,3-triazoles. 1 The exceptional stability of 1,2,3-triazoles and the availability of a reliable synthesis leading to these heterocycles have enabled widespread applications of this previously underutilized class of azoles in medicinal chemistry, chemical biology and materials science. 2 In contrast to the 1,4-disubstituted-1H-1,2,3-triazoles, general and regioselective routes leading to the 1,5-regioisomers are not as well developed. [3][4][5][6][7][8] Although syntheses relying on the nucleophilic attack by the acetylide at the electrophilic terminal nitrogen of the azide are known, 9 the requirement for the stoichiometric lithium or magnesium acetylide reagent imposes obvious limitations on the range of functional groups that are compatible with these processes. Reported here is a mild and experimentally simple catalytic method for the generation of the reactive acetylides which readily react with organic azides resulting in the exclusive formation of 1,5-disubstituted triazoles.We envisioned that the high acidity of aryl acetylenes in dimethylsulfoxide [10][11][12] should allow formation of the reactive acetylide species by treatment of the alkyne with a hydroxide or fokin@scripps.edu. Supporting Information Available. Experimental procedures, characterization data, copies of 1 H NMR and 13 C NMR spectra. This material is available free of charge on the Internet at http://pubs.acs.org. alkoxide base in this solvent. In fact, formation of acetylide intermediates has been proposed by Ishikawa and co-workers in their studies of the alkynylation of ketones. 13 Screening of various hydroxides and alkoxides confirmed this hypothesis, revealing that anhydrous sodium, potassium, cesium hydroxides, and aqueous tetramethylammonium and benzyltrimethylammonium hydroxides catalyze formation of 1,5-diarylsubstituted-1H-1,2,3-triazoles in DMSO at room temperature (Table 1). NIH Public AccessDry DMSO and less nucleophilic bases such as potassium tert-butoxide can also be used to minimize hydrolysis of substrates which contain base-sensitive functionalities. In many cases, the desired products precipitated upon addition of 5-20× volume of ice-cold water and were isolated by simple filtration. Reactions in DMSO afforded higher isolated yield than in DMF on larger scale and at higher concentration. Although tetraalkylammonium hydroxides resulted in the slightly diminished yield of the product compared to powdered KOH, the shorter reaction time and the experimental convenience of using aqueous base solutions make tetraalkylammonium hydroxides advantageous catalysts for practical reasons.While o...

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Calls to change the residency selection process have increased in recent years, with many focusing on the need for holistic review and alternatives to academic metrics. One aspect of applicant performance to consider in holistic review is proficiency in behavioral competencies. The Association of American Medical Colleges (AAMC) developed the AAMC Standardized Video Interview (SVI), an online, asynchronous video interview that assesses applicants’ knowledge of professionalism and their interpersonal and communication skills. The AAMC worked with the emergency medicine community to pilot the SVI. Data from 4 years of research (Electronic Residency Application Service [ERAS] 2017–2020 cycles) show the SVI is a reliable, valid assessment of these behavioral competencies. It provides information not available in the ERAS application packet, and it does not disadvantage individuals or groups. Yet despite the SVI’s psychometric properties, the AAMC elected not to renew or expand the pilot in residency selection. In this Invited Commentary, the authors share lessons learned from the AAMC SVI project about introducing a new tool for use in residency selection. They recommend that future projects endeavoring to find ways to support holistic review engage all stakeholders from the start; communicate the value of the new tool early and often; make direct comparisons with existing tools; give new tools time and space to succeed; strike a balance between early adopters and broad participation; help stakeholders understand the limitations of what a tool can do; and set clear expectations about both stakeholder input and pricing. They encourage the medical education community to learn from the SVI project and to consider future partnerships with the AAMC or other specialty organizations to develop new tools and approaches that prioritize the community’s needs. Finding solutions to the challenges facing residency selection should be a priority for all stakeholders.