A glove box to enable transition metal-catalyzed reactions in the Yudin lab

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Amphoteric molecules – bifunctional structures equipped with orthogonal nodes of reactivity – have been the focus of our research program. Over the past 24 months we have published 3 pivotal papers that describe: (a) a new way of installing heterocyclic grafts in the structures of macrocycles (Nature Chem. 2016, 8, 11050), (b) mechanistic underpinnings of boride transfer reactions (Nature Chem. 2017, in press), and (c) showcaser boron’s unique coordination preferences in heteroatom-rich protein environments (Nature Chem. 2017, 9, 731). We are prevented from making advances in macrocycle chemistry and boron chemistry by the absence of a dedicated glovebox. In fact, we performed an internal vote and glovebox came up as the top choice for new equipment. Given how hard my students work, I am certain that the glovebox will be in use 7 days a week. Chemicals in a glovebox reflect the research interests of the lab housing the unit and cross-contamination with someone else’s material is the number one reason the instrument should not be shared. My students do not have any place where they can perform experiments that require inert atmosphere, yet it is also clear that the next wave of our advances will likely arise from transition metal catalyzed transformations of macrocycles as well as heteroatom-rich organoboron compounds. A delay in acquisition of the glovebox will make it difficult to make rapid advances in an extremely competitive field. However, if we obtain the glovebox, we will be able to build on our recent breakthroughs and design transition metal-catalyzed transformations of macrocycles in order to modulate their polar surface areas. At the moment, none of our research on macrocycles involves metal catalysis that requires inert atmosphere. However, we have published influential accounts suggesting that synthetic manipulation of macrocycles can drastically affect their properties. It stands to reason that adding an unexplored capability will be akin to putting our program into a new gear. Besides the obvious loss of ability to publish high-leven papers, our patent position will suffer. Most alarmingly, not having a means to carry out exciting projects at the interface of complex molecules synthesis and metal catalysis will affect my ability to recruit top talent into my lab and will remove an attractive component out of training the HQP. Pharmaceutical companies (Merck, BMS, Gilead) routinely hire individuals out of my lab, which suggests that the training we offer is deemed valuable. We have exhausted non-metal mediated ways of making macrocycles and my students need to expand their horizons. Our lab feels that metal catalysis is the likeliest modality that will assure rapid advances in strategically important areas of our research.