New phase transfer catalysts are reported for the first example of an organocatalytic asymmetric conjugate addition of cyanide with acetone cyanohydrin. Utilizing an accessible cupreidinium salt and a cyanation reagent suitable for industrial scale, this reaction holds significant promise for practical asymmetric synthesis. Additionally, the reported catalysts were developed as a result of gaining key structural insights via X-ray analysis of a series of catalysts of varying efficiencies and asymmetric induction.

A class of easily accessible and readily tunable chiral phase transfer catalysts based on 6’-OH cinchonium salts was found to efficiently catalyze an unprecedented highly enantioselective Darzens reaction of α-chloro ketones and aldehydes, which directly produces optically active chiral epoxides from readily available carbonyl compounds.

This work describes two distinct routes to prepare pyrazolo[1,5-alpha]pyrimidin-7-ones and two distinct routes to prepare pyrazolo[1,5-alpha]pyrimidin-5-ones. Use of 1,3-dimethyluracil as the electrophile in the preparation of the pyrimidin-5-one regioisomer represents a correction of previously reported results. Also, a novel reaction to prepare this isomer was identified and the reaction mechanism elucidated. This work provides the experimentalist with complimentary synthetic pathways that afford either the pyrimidin-7-one or the pyrimidin-5-one regioisomer.

During the Spring 2020 semester, many institutions abruptly transitioned their courses from face-to-face instruction to remote learning in response to the COVID-19 pandemic. To address the unique challenges posed by the remote teaching and learning modality, our department used mobile technology to adapt empirically validated instructional strategies for use in our remote courses. At Merrimack College, all faculty and students have iPads and Apple Pencils, and the members of the Department of Chemistry and Biochemistry have incorporated this mobile technology into all of our course offerings. Our continued use of this technology eased the transition for both faculty and students by promoting course continuity and decreasing the cognitive load imposed by the transition. Survey responses suggest that students appreciated the structure provided by scaffolded course materials and synchronous class meetings, which helped keep them engaged in their chemistry courses. Coupling active learning instruction with the Zoom video conferencing platform allowed students to connect with the instructor and other students; this was highly valued by our students. Overall, we can conclude that universal access to technology, creating community using videoconferencing software, and intentional pedagogical choices to incorporate active learning created a positive learning environment for students.

Significant advances have been made in the development of catalytic 1,2-asymmetric cyanations using both chiral metal and organic catalysts. [1] In contrast, only a few highly enantioselective catalytic conjugate additions of cyanide ions have been realized despite the potential of such transformations in providing efficient enantioselective access to synthetically valuable chiral building blocks. [2] The first breakthroughs were reported by Jacobsen and co-workers, who described chiral Al-Salen [3] and bimetallic cooperative catalyst systems [4] for the enantioselective conjugate additions of trimethylsilyl cyanide (TMSCN) to a,bunsaturated imides. Shibasaki, Kanai, and co-workers reported two chiral bifunctional catalysts derived from gadolinium, strontium, and different asymmetrically prepared or carbohydrate-based chiral ligands for a highly enantioselective 1,4-addition of cyanide with HCN/trialkylsilyl cyanides to a,b-unsaturated N-acyl pyrroles [5] and enones, [6] respectively. Feng [7] and co-workers have reported a modular titanium catalyst for the cyanation of alkylidine malonates. Very recently, Ohkuma [8] and co-workers disclosed a chiral Ru complex for the conjugate addition of TMSCN to enones. These existing reactions, while representing remarkable success in establishing general substrate scope and high catalyst efficiency, require the use of various trialkylmetal cyanides in super-stoichiometric amounts. Thus, we became interested in the development of highly enantioselective catalytic 1,4-additions of cyanide with readily accessible and easy to handle cyanation reagents.Chiral phase-transfer catalysis has been developed as an effective strategy for the activation of practical cyanation reagents, such as KCN [9] and acetone cyanohydrin, [10] for asymmetric 1,2-additions of cyanides. On the other hand, this strategy has so far been attempted only with 1,4-additions of cyanide to nitroalkenes. [11] These attempts have so far been met with limited success. Our recent development of cupreinium salts 1, as highly enantioselective phase-transfer catalysts for an asymmetric Darzens reaction, [12] prompted us to explore them for the asymmetric conjugate addition of cyanide. Similar to other known bifunctional phase-transfer catalysts that bear a hydrogen-bond-donor moiety, [13][14][15] cupreidinium salts CPD-1, could in principle mediate phasetransfer catalysis by their association with an anionic cyanation species, presumably a cyanide or cyanoalkoxide ion, by simultaneous ion-pair and hydrogen-bonding interactions (I, Scheme 1). Alternatively, CPD-1 could promote the conjugate addition by simultaneous interactions with both the cyanation species and the enone (II, Scheme 1).We first investigated the asymmetric conjugate addition of acetone cyanohydrin to enone 5 a. As the equilibrium between cyanohydrin and the enone is known to favor the latter under basic conditions, [16] we reasoned that chiral phase-transfer catalysis might provide an attractive strategy to address the 1,2-vs. 1,4-chemoselectivity ...