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Daniel Nasrallah: My role was to support the Lisso team by synthesizing the two intermediates used in the key allene Diels-Alder step. I used the material to further optimize this pivotal reaction under more standard conditions.

Laura Wonilowicz: The main part of my role in the total synthesis of lissodendoric acid A was to help develop the asymmetric synthesis that allowed us to complete an enantioselective synthesis. This involved the development of a key intermediate in enantioenriched form and using it to access the natural product.

Bo Li: I was involved in the computational prediction of the reaction mechanism, specifically on the desymmetrization mechanism of the intermediate π-allylnickel complexes. I worked with Qianzhen, Shuming, and Ken on finishing these calculations.

Francesca Ippoliti: I worked on the total synthesis of lissodendoric acid A. This project spanned my whole graduate school career, as I started with preliminary experiments of Diels–Alder reactions between pyrones and azacyclic allenes and worked on many routes to the natural product over the years, culminating in its total synthesis.

Evan Darzi: The biggest challenge was pulling together the sparse allene literature that was scattered over many decades to start to understand how to think about the reactivity in a predictive manner.

Shuming Chen: From the computational side, it was coming up with a valid model and explanation for the observed selectivity.

Laura Wonilowicz: One of the biggest challenges was ensuring selectivity in our synthetic steps to allow us to access the desired form of lissodendoric acid A. Another challenge was managing synthetic material to access complex compounds and develop reaction conditions.

Nathan Adamson: The development of the enantiospecific cyclic allene Diels-Alder reaction as the key step for the synthesis was challenging and required a lot of optimization.

Evan Darzi: We had team members that specialized in theoretical chemistry, methodology development, total synthesis, catalysis, and med chem. Each of them was flexible in learning more about their teammates area of expertise so we could work together as a high functioning team.

Daniel Nasrallah: The diversity of scientists on this project is exactly why such significant work could be accomplished. Everyone brought their individual strengths to the project and allowed us to overcome obstacles.

Dominick Witkowski: Different synthetic and computational experience from all team members. Also, everyone's creativity and work ethic.

Laura Wonilowicz: In developing the total synthesis, each teammate brought invaluable skills that enabled our success. Some of these included synthetic strategy planning, reaction design, and working on a small scale.

Kendall Houk: New frontiers in the use of strained intermediates in synthesis.

Bryan Simmons: This work is important and exciting because it offers synthetic chemists a new way to create bonds and forge ring structures that were previously unexplored.

Neil Garg: these studies provide access to valuable structures while also challenging the norms of reactivity and dispelling long-standing ways of thinking.

Maude Giroud: Strained intermediates such as cyclic dienes and trienes are arguably understudied and underused, and this work highlights the potential of these intermediates for use in organic synthesis.

Laura Wonilowicz: The development of strained intermediate chemistry, including cyclic allenes and cyclic trienes, is exciting for both fundamental chemistry knowledge and potential applications. We have gained new knowledge in the structure, reactivity, and synthetic feasibility of these fleeting molecules. We hope this will encourage the further exploration of strained intermediates. As these methods can be applied to the synthesis of complex molecules, we hope that they will be valuable to industries such as pharmaceuticals.

Evan Darzi: I think you will see more and more work leveraging these compact reactive molecules that not only react fast but have the ability to transfer stereochemical information quickly.

Bryan Simmons: I see the biggest impact of this being in the pharmaceutical industry, where medicinal chemists are looking for new and facile ways to create life-saving small-molecule drugs.

Shuming Chen: It will encourage people to come up with other creative ways of using reactive intermediates for building complexity. I think it will be most significant to pharmaceutical chemistry and total synthesis.

Ana Bulger: potentially, in complex-molecule synthesis, we have a better understanding of regio-, diastereo- and enantioselective nature of the reactions of these species, which makes them more easily adoptable into synthetic planning

Maude Giroud: I see a big impact initially in academia, where strained intermediates might be used more for method development and total syntheses, and eventually in industry, depending on the availability of the precursors.

Nathan Adamson: I think the biggest impact will be toward the synthesis of new chemical structures with a high degree of 3D character that can be used for complex molecule synthesis or as medicinal chemistry building blocks.

Evan Darzi: These allenes can be used to rapidly access heterocycle rich libraries for application in medicinal chemistry and have already been demonstrated to short sequence total synthesis of complex natural products with bioactivity.

Daniel Nasrallah: I think this work will begin to be further and further adopted into drug discovery and process chemistry.

Dominick Witkowski: Methodologies could be used in drug discovery

Ana Bulger: potentially for materials chemistry, pharmaceutical, or agriscience applications, and more.

Laura Wonilowicz: We hope that this work will find application in industries where complex molecules are crucial. For example, this work may be beneficial to the pharmaceutical or agriculture industries, where access to molecules that are often hetereoatom-containing and enantioenriched is imperative.

Andrew Kelleghan: Continuing to push the limits of strained molecules by challenging preconceived notions about what is "too reactive to be useful".

Bryan Simmons: I see this work developing by labs exploring the utility of this in creating new chemical structures and expanding the methodology to forge new bonds and heterocycles.

Daniel Nasrallah: I think there could be a real explosion of interest and publications demonstrating the utility of these types of methods to so many different areas of chemistry.

Joyann Donaldson: It is still the tip of the iceberg for the power of this chemistry.

Maude Giroud: It is only the early days of metal-promoted annulations with strained intermediates and I am sure that many more annulations can be thought, expanding the toolbox of strained intermediates.

Francesca Ippoliti: I think we will see more work being done on understanding the transfer of stereochemical information and selectivity in reactions involving these strained intermediates. I hope we will see strained cyclic dienes and trienes being used by more synthetic research groups to tackle difficult total syntheses.

Bryan Simmons: The constant drive to explore the unknown and push the boundaries of synthetic chemistry.

Daniel Nasrallah: Getting to work on really cool chemistry that is exciting to explore every day.

Neil Garg: Challenging long-standing beliefs in the field and collaborating with insanely bright people.

Michael Yamano: Achieving something impactful that’s never been accomplished before.

Nathan Adamson: Our team is motivated by the idea of exploring the extremes of what chemistry can do. Strained intermediates are fleeting species with an extremely short lifetime and yet we are able to harness them to do cool and complex chemistry. What more motivation could we need?

Evan Darzi: It is really hard to solve difficult problems if you are siloed in your core discipline.

Shuming Chen: Experimental-computational collaboration is incredibly important to the chemical sciences. Without modern computational tools, our ability to understand and control reactions would be severely limited.

Joyann Donaldson: Collaboration allows for idea sharing and enables greater impact than the individuals could have independently.

Maude Giroud: Collaboration is extremely important not only in chemical sciences but in science in general. Joining forces from different areas of expertise can help solve problems that one person alone could not.

Michael Yamano: Collaboration is key in order to accelerate research. The more good ideas you have the faster you can move projects and more creative directions can be pursued.

Nathan Adamson: We rely on each other and our collaborators to tackle the important problems from multiple angles. Sometimes, a problem requires good experimental work and other times, it requires computational or theoretical work and no one is an expert in every field.

Andrew Kelleghan: Constantly listening, sharing ideas, responding rapidly to new data generated.

Ana Bulger: Reporting reproducible procedures that are checked internally, working on teams where there is healthy discourse within the team and with others outside the team.

Laura Wonilowicz: To me, a good research culture means that it is okay to make mistakes while learning. It is important to me that researchers can grow, which often requires trial and error.

Francesca Ippoliti: Good research culture means that all of the members of the team support each other through all of the challenges that accompany a research project. The team is willing to be flexible and strategize how to solve problems together.

Andrew Kelleghan: Enabling access to new medicines and agrochemicals and providing entryways for students to become interested in STEM.

Daniel Nasrallah: By providing new methods for making molecules that are easier and safer while also increasing the complexity of products formed. This gives scientists the tools to be able to solve some of the world's problems.

Joyann Donaldson: So many incredible developments are linked to the chemical sciences. Perhaps most importantly new medicines but also fertilizers/pesticides for safe food, OLEDs, etc.

Ana Bulger: the chemical sciences are opening up doors by developing new reactions and new understanding of these reactions, which makes them easier and more well-adopted for scientists in industry.

Maude Giroud: Chemical sciences are everywhere, from healthcare to food science and energy, among others. As chemists, we have the possibility to contribute to all these health, environmental and technological challenges.

Laura Wonilowicz: The chemical sciences are making the world a better place through the central role that chemistry plays. Because of this, advances in chemistry can mean valuable applications to multiple industries, from pharmaceuticals, to agriculture, to energy.

Nathan Adamson: The discovery of the new chemical methods enables the synthesis of new types of structures that are difficult to access by other means. This can enable faster discovery of new pharmaceuticals, agrochemicals, polymers, and other useful materials that can have a positive impact on human and environmental health.

Kendall Houk: Learn everything you can, work hard, and enjoy making an impact on science.

Daniel Nasrallah: If you are excited about the things you can learn, explore, and discover, you are in the right place. A career in the chemical sciences means you get to try new things all the time, solving problems and making a difference. This is a very exciting and rewarding career.

Neil Garg: Be proactive in finding mentors and supportive environments.

Ana Bulger: My advice would be to keep an attitude of perseverance because in science, there will be a lot of failure, but learning how to deal with that failure and solve problems is what makes us into the best scientists we can be

Maude Giroud: If you are curious, motivated and like problem-solving, then chemistry is probably for you!

Laura Wonilowicz: I would advise a young person considering a career in chemical sciences to try their best not to get discouraged by setbacks. Although chemistry can be challenging, it is extremely rewarding.

Michael Yamano: I would give them the advice that you get out of it what you put in. If you put in the work, you can get a lot out of it.

Bo Li: I personally recommend always considering how to integrate ideas across different subjects and domains. This is how I see many unique contributions are made.

Francesca Ippoliti: Research in the chemical sciences can be very rewarding when experiments go well, but most of your experiments will fail. Be persistent!

Nathan Adamson: I would tell them to not be afraid to try new things and never talk yourself out of running an easy experiment that could have a big payoff. It's natural to fail (and even fail often) when you are at the forefront of what is possible, but never let the fear of failure hold you back from trying new things. The biggest breakthrough might be just around the corner.