David W.C. MacMillan: Nobel Prize lecture in chemistry 2021

Summary

David MacMillan's lecture delves into the world of asymmetric organocatalysis, a field he pioneered. He explains the significance of catalysis in daily life and industrial processes, the importance of asymmetry in molecular reactions, and the innovative approach of using organic molecules as catalysts. MacMillan's journey from his PhD to becoming a distinguished professor at Princeton is highlighted, along with the groundbreaking experiments and discoveries that have positioned organocatalysis as a key player in sustainable chemistry and its applications in creating perfumes, recyclable plastics, and life-saving medicines.

Takeaways

• 🎓 David MacMillan was born in Scotland in 1968 and obtained his PhD from the University of California, Irvine in 1996. He is now a distinguished professor at Princeton University.
• 🏆 MacMillan expresses gratitude to the Royal Swedish Academy of Sciences and the Nobel Committee in Chemistry, acknowledging the significance of the Nobel Prize and congratulating co-recipient Benjamin List and other laureates.
• 🔍 The script introduces the concept of 'asymmetric organocatalysis' by breaking down the term into 'catalysis', 'asymmetric', and 'organo', highlighting their importance in chemistry.
• ⛰️ Catalysis is described as a process that lowers the energy barrier for chemical reactions, making them easier, faster, and enabling new reactions to occur.
• 🌱 The impact of catalysis on the world is vast, including its crucial role in the production of food through the conversion of nitrogen to ammonia, which is essential for sustaining the global population.
• 🔄 Asymmetric catalysis is crucial in creating one mirror image of a compound over another, which is important in medicine where different mirror images can have different effects on the body.
• 🧪 The term 'organo' in catalysis refers to the use of organic molecules as catalysts, which are often inexpensive, safe, sustainable, and recyclable, contrasting with the use of metals.
• 💡 MacMillan's 'eureka' moment during his time at Harvard led to the development of the concept of organocatalysis, using organic molecules as catalysts instead of metals.
• 🌟 The success of organocatalysis is attributed to its ability to be a generic activation mode, applicable to a wide range of chemical reactions, not just one.
• 🌱 The script highlights the interdisciplinary nature of organocatalysis, merging with other fields such as photoredox catalysis to create sustainable chemical reactions powered by visible light.
• 🌐 Organocatalysis is presented as a democratizing force in catalysis, making it accessible and affordable for researchers worldwide, regardless of their country of origin.

Q & A

Who is David MacMillan and what is his current academic position?

David MacMillan was born in 1968 in Bellshill, Scotland. He obtained his PhD in 1996 from the University of California, Irvine. He is currently the James McDonald Distinguished University Professor at Princeton University in the United States.

What notable award did David MacMillan receive in 2021?

David MacMillan received the Nobel Prize in Chemistry in 2021.

What is asymmetric organocatalysis?

Asymmetric organocatalysis is a type of catalysis that uses small organic molecules to accelerate chemical reactions while selectively producing one mirror image (enantiomer) of a molecule over the other.

Why is catalysis important in chemical reactions?

Catalysis is important because it makes chemical reactions easier and faster by lowering the energy barrier required for the reactions to occur, allowing new chemical reactions to take place that otherwise might not happen spontaneously.

How does catalysis impact the global population?

Catalysis impacts the global population by enabling the production of ammonia from nitrogen, which is essential for creating fertilizers that help sustain the food supply for the world's population. This catalytic reaction supports the nutrition of roughly 50% of the world's population.

What are the two major branches of asymmetric catalysis that existed before organocatalysis?

The two major branches of asymmetric catalysis before organocatalysis were biocatalysis, which uses enzymes from living systems, and metal catalysis, which uses metals to produce one mirror image selectively.

What was David MacMillan's eureka moment related to organocatalysis?

David MacMillan's eureka moment occurred when he realized that organic components of catalysts, specifically enamines, could be used to catalyze chemical reactions without the need for metals, leading to the development of organocatalysis.

What is the significance of the imidazolenones in MacMillan's research?

Imidazolenones were significant in MacMillan's research because they were inexpensive, made from natural building blocks, and effective in catalyzing reactions to produce one enantiomer over the other, achieving over 90% enantiomeric excess.

How has organocatalysis impacted the production of perfumes and plastics?

Organocatalysis has been used to produce perfumes such as Lily of the Valley and rose-smelling perfumes. It also plays a role in making plastics recyclable by breaking down polymers into monomers that can be reused, contributing to a more sustainable plastic economy.

What potential future applications does organocatalysis have?

Future applications of organocatalysis include making pharmaceuticals, materials, and chemicals in a more sustainable and efficient manner. It is expected to play a significant role in creating sustainable technologies for an expanding global population.

Who are some of the key individuals and groups David MacMillan acknowledged in his lecture?

David MacMillan acknowledged his PhD advisor Professor Larry Overman, his postdoctoral advisor Professor David Evans, his research groups at UC Irvine, Berkeley, Caltech, and Princeton, his wife Jean, his children, his mother-in-law Julie, and his siblings Ian and Lorraine. He also dedicated his talk to Carlos Barbas, a pioneer in organocatalysis, and his parents.

Outlines

00:00

🏆 Introduction and Asymmetric Organocatalysis

David MacMillan, born in 1968 in Scotland, is a distinguished professor at Princeton University. He expresses gratitude to the Royal Swedish Academy of Sciences and the Nobel Committee in Chemistry for the 2021 Nobel Prize, shared with Benjamin List. MacMillan reflects on the past two months and the common question he's been asked about asymmetric organocatalysis. He begins his lecture by defining 'catalysis' as a process that facilitates and accelerates chemical reactions, using the analogy of walking over a hill to illustrate the concept. He emphasizes the importance of catalysis in various aspects of life, including the production of food through the conversion of nitrogen to ammonia, a process essential for sustaining the global population. MacMillan also highlights the significant role of catalysis in industrial chemical reactions and the world's GDP.

05:02

🧪 The Significance of Asymmetry in Chemistry

MacMillan delves into the concept of 'asymmetric' by drawing an analogy with human hands and feet, which are mirror images but not superimposable. He explains that in organic chemistry, molecules can exist as mirror images that are distinct due to their non-superimposability. Differentiating between these mirror images, known as enantiomers, can be challenging and typically requires expensive equipment and time. However, the human sense of smell can discern these differences, as illustrated by MacMillan's daughter's ability to distinguish between two enantiomers by smell. This distinction is crucial in biology and medicine, as one enantiomer of a molecule can be beneficial while the other may be harmful or toxic. The pharmaceutical industry relies heavily on the ability to produce one enantiomer selectively, which is where asymmetric catalysis plays a vital role.

10:02

🔬 The Emergence of Organocatalysis

The term 'organo' is introduced by reflecting on the branches of asymmetric catalysis in 1996, which included biocatalysis and metal catalysis. MacMillan's journey in organocatalysis began during his PhD at UC Irvine under the mentorship of Professor Larry Overman and continued at Harvard with Professor David Evans, a pioneer in asymmetric catalysis. MacMillan's 'eureka' moment came when considering the use of organic molecules as catalysts, given their advantages over metal catalysts, such as being inexpensive, safe, sustainable, and recyclable. He moved to Berkeley as an assistant professor, inspired by advice from Professor Eric Herrera to focus on high-impact research. This led him to pursue organocatalysis, with the ambitious idea of developing a catalyst that could work for hundreds of different reactions.

15:04

🌟 The Breakthrough in Asymmetric Organocatalysis

MacMillan recounts the initial challenges and excitement in developing an organocatalyst that could selectively produce one enantiomer in the Diels-Alder reaction, a fundamental process in chemistry. The first attempt resulted in a 48% excess of one enantiomer, far from the 90% threshold needed for serious consideration by the chemistry community. After six nerve-wracking months, the team developed a new catalyst, imidazolenones, derived from phenylalanine and acetone, which successfully achieved the desired selectivity. This breakthrough was a significant step in establishing organocatalysis as a viable field, and MacMillan's first manuscript on the subject introduced the term 'organocatalysis' and the concept of a 'generic activation mode,' suggesting the potential for the catalyst to work across many reactions.

20:04

🔬 Advancing Organocatalysis and Photoredox Catalysis

Following the initial success, MacMillan and his team faced challenges in applying their organocatalyst to other reactions, leading to the development of a second-generation catalyst. This advancement significantly expanded the scope of organocatalysis. MacMillan acknowledges the contributions of other researchers in the field, emphasizing that organocatalysis was not the work of a single individual but a collective effort. He discusses the integration of organocatalysis with photoredox catalysis, harnessing visible light to drive chemical reactions, which has applications in creating sustainable technologies. The collaboration with postdoc Dave Nisevich led to the development of photoredox catalysis, which has since grown into a significant field.

25:06

🌿 Applications and Future of Organocatalysis

MacMillan explores the various applications of organocatalysis, including its use in creating fragrances and perfumes, developing recyclable plastics, and most notably, in the synthesis of pharmaceuticals. He highlights the democratizing effect of organocatalysis, making催化ysis accessible and affordable worldwide, thus enabling researchers from any country to contribute to the field. Looking to the future, he emphasizes the need for sustainable catalytic processes, including organocatalysis, biocatalysis, photocatalysis, and electrocatalysis, to meet the needs of a growing global population responsibly.

30:08

🙌 Personal Acknowledgments and Dedications

In the concluding part of the script, MacMillan expresses his gratitude to the people who have supported him throughout his journey. He thanks his wife Jean, his family, his mother-in-law Julie, his siblings Ian and Lorraine, and the educators who have influenced his life. He dedicates his talk to three individuals who have passed away: Carlos Barbas, a pioneer in organocatalysis; and his parents, who were always supportive and believed in his potential. MacMillan's heartfelt acknowledgments reflect the collaborative and personal nature of scientific discovery.

Keywords

💡Asymmetric Organocatalysis

Asymmetric organocatalysis is a specialized branch of catalysis that focuses on the selective creation of one enantiomer, or mirror image, of a molecule over another. This is crucial in chemistry because many molecules exist as mirror images, and these images can have vastly different biological activities, as seen in pharmaceuticals where one enantiomer might be beneficial while the other could be harmful. In the script, David MacMillan discusses the importance of asymmetric organocatalysis in creating specific enantiomers for use in medicine and other applications.

💡Catalysis

Catalysis is a fundamental concept in chemistry referring to the acceleration of a chemical reaction by a substance, known as a catalyst, which increases the reaction rate without being consumed in the process. Catalysts lower the energy barrier for a reaction, making it proceed more efficiently. In the video, MacMillan uses the analogy of walking over a hill to explain how catalysis makes chemical reactions easier and faster, and he discusses its significant impact on the world, including its role in the production of food and medicines.

💡Enantiomers

Enantiomers are one of the two stereoisomers that are mirror images of each other but are not identical, much like left and right hands. They have the same physical and chemical properties but differ in the way they interact with plane-polarized light and with other chiral substances. In the script, MacMillan explains the concept of enantiomers using gloves as an analogy, highlighting their importance in biological systems and their implications in medicine due to their different interactions with the human body.

💡Organocatalysis

Organocatalysis is a type of catalysis that uses organic molecules as catalysts. Unlike traditional metal catalysis, organocatalysis often involves more sustainable, non-toxic, and readily available organic compounds. MacMillan's research in the script focuses on organocatalysis, which he pursued as an alternative to metal catalysis, aiming to develop catalysts that could be used for a wide range of reactions.

💡Diels-Alder Reaction

The Diels-Alder reaction is a [4+2] cycloaddition reaction between a conjugated diene and a dienophile, creating a six-membered ring. It is a fundamental reaction in organic chemistry and was the subject of the 1950 Nobel Prize in Chemistry. In the script, MacMillan describes the use of organocatalysis in the Diels-Alder reaction as a test case for this new catalytic approach, marking a significant milestone in the development of organocatalysis.

💡Imidazolenones

Imidazolenones are a type of organocatalyst that MacMillan and his team developed for use in asymmetric catalysis. These catalysts are derived from phenylalanine, an amino acid, and acetone, making them inexpensive and accessible. In the script, MacMillan discusses the development of imidazolenones as a second-generation catalyst that allowed them to achieve high enantioselectivity in reactions.

💡Enantioselectivity

Enantioselectivity is a measure of a reaction's ability to produce one enantiomer over another. It is typically expressed as a percentage, with higher percentages indicating greater selectivity for one enantiomer. In the context of the script, MacMillan's team aimed to increase the enantioselectivity of their reactions from an initial 48% to a more significant 90%, which would be taken seriously by the chemistry community.

💡Photoredox Catalysis

Photoredox catalysis is a type of catalysis that uses light as the energy source to drive chemical reactions. It is a relatively new field that has grown significantly and is related to organocatalysis. In the script, MacMillan explains how his team became interested in combining the principles of organocatalysis with photoredox catalysis to perform new types of transformations, harnessing the power of visible light to drive reactions.

💡Catalytic Cascades

Catalytic cascades refer to a series of reactions where one catalyst enables multiple sequential reactions to occur in a single operation. This approach is inspired by the way nature uses enzymes in biochemical pathways to create complex molecules from simple ones. MacMillan discusses the concept of using catalytic cascades in his lab to emulate nature's efficiency and create complex molecules like strychnine.

💡Sustainable Chemistry

Sustainable chemistry is the design of chemical products and processes that reduce or eliminate the use and generation of hazardous substances. In the script, MacMillan emphasizes the importance of developing sustainable catalytic processes, such as organocatalysis, photocatalysis, and electrocatalysis, to meet the needs of an expanding global population in an environmentally responsible way.

Highlights

David MacMillan's introduction as the James S. McDonnell Distinguished University Professor at Princeton University.

MacMillan's gratitude towards the Royal Swedish Academy of Sciences and the Nobel Committee in Chemistry.

The explanation of what catalysis is and its importance in facilitating chemical reactions.

The significance of the Haber-Bosch process in converting nitrogen to ammonia for food production.

The impact of catalysis on 90% of industrial-scale chemical reactions and 35% of the world's GDP.

The concept of asymmetric catalysis and its relevance to the production of medicines.

MacMillan's personal journey from his PhD at UC Irvine to his influential work in asymmetric catalysis.

The introduction of organocatalysis as a novel approach using organic molecules as catalysts.

The development of the imidazolenone catalysts and their success in achieving high enantioselectivity.

The naming of the field of organocatalysis and its importance for the growth of the discipline.

The concept of a generic activation mode, suggesting the broad applicability of organocatalysis.

The evolution of organocatalysis into photocatalysis and its potential for sustainable chemical reactions.

The application of organocatalysis in the production of fragrances and perfumes.

The role of organocatalysis in creating recyclable plastics and contributing to a circular economy.

The use of organocatalysis in the development of pharmaceuticals, exemplified by the drug for chronic migraines.

The democratization of catalysis through organocatalysis, making it accessible worldwide for education and research.

MacMillan's reflections on the future of organocatalysis and its role in sustainable technologies.

A heartfelt dedication to the pioneers of organocatalysis, including Carlos Barbas, and MacMillan's family.

Transcripts

david macmillan was born in 1968 in

bell's hill scotland

he obtained his phd in 1996 from the

university of california irvine

he is currently the james mcdonald

distinguished university professor at

princeton university in the united

states

david mcmillan

i now welcome you on to the stage

we are very much looking forward to your

lecture

okay i'd like to begin by thanking the

royal swedish academy of sciences i'd

like to thank the nobel committee in

chemistry

i'd like to congratulate the other

co-recipient of this prize benjamin list

and all of the other 2021 nobel prize

winners

and i'd like to thank you all for your

attention this morning

the last two months has really been just

remarkable for me it's been an extremely

exciting time

and during that time i've been asked

many many questions but probably the

number one question i've been asked is

this one which is shown here what is

asymmetric organocatalysis

so i thought i'd begin my talk today by

breaking down each of these terms

the first term i want to tell you about

is catalysis what is catalysis

well catalysis is related to chemical

reactions

if you look around you right now

everything is made from a chemical

reaction in fact if i look in my office

and this is my desk every component

every material that's in my office is

made by a chemical reaction

now if we look at all those different

chemical reactions and we actually hone

in on one of them for example this one

shown here this is actually the chemical

reaction to make caffeine this is the

molecule which is found in your coffee

it turns out that all chemical reactions

require energy most chemical reactions

do not happen spontaneously

and to represent that most chemists use

what's called an energy diagram

now i'm not going to be so technical

here i just want to show you what this

energy diagram looks like and one aspect

i like about this is when i teach this

to undergraduates i always explain it in

the following way

imagine every night when you're going

home you actually have to walk over a

hill

to walk over a hill to get home would

obviously require a lot of energy every

single night

what catalysis does catalysis actually

lowers the barrier and in fact

introduces a tunnel to make it so much

easier for you to get home every night

and in the same way it does this for

chemical reactions it makes all chemical

reactions easier and faster so that's

exactly what catalysis is reactions are

easier faster and in many cases allows

new chemical reactions to take place

now you may ask yourself does catalysis

really impact the world

and it does and it does in many

different interesting ways but i thought

i'd just show you a few

so here's the first one this is the

population of our earth over the last

1000 years and you can see here it's

been pretty stable during that time

frame

till the beginning of the 20th century

and at that point you see this rapid

inflection

and at this moment it climbs up to eight

billion people on earth

now it turns out it would not have been

possible to have these eight billion

people on earth without this one

catalytic reaction which is shown here

this is the conversion of nitrogen over

to ammonia

now you may ask yourself well why do we

need ammonia

well we need ammonia to make food and we

would not have enough food on our planet

for those eight billion people without

this one catalytic reaction and in fact

if you think about your body right now

and you think about all the building

blocks that are in your body

50 of those building blocks contain

nitrogens that came from this one

catalytic reaction

now other ways that catalysis impacts

our world is that 90

of industrial-scale chemical reactions

at the present time actually use

catalysis and 35 of the world's gdp is

also based on catalysis

and this number is actually only going

to go up over the next couple of decades

as we move towards more and more

sustainable processes

now if you're wondering how does

catalysis impact your day-to-day life it

does so in many different ways we've

talked already about why we need it to

make food but also we need it to make

medicines we need it for solar cells we

need it for diagnostics even the global

manufacturing of polymers and materials

we need catalysis so clearly catalysis

is important for our world

so that's great that's catalysis but the

next part is what about asymmetric what

does asymmetric mean

well it turns out it's actually pretty

easy to describe what asymmetric means

to non-chemists because most people on

earth have two hands or you have two

feet and if you look at your two hands

we know that they're in fact mirror

images of each other

those mirror images are similar but

they're still different they're

different because they're not

superimposable which makes them

asymmetric

so how do we know that well we know that

for example if you were to take a

left-hand glove you know that it fits on

your left hand

but if you take that same glove and try

to put it on your right hand you know

that your right hand will not recognize

that glove it simply doesn't fit and

that's what you call it being

asymmetric now what's really interesting

in organic chemistry the same phenomenon

happens and these are two organic

molecules which are in fact mirror

images of each other but they're similar

but they're still different

which brings up an interesting question

in a lab how do you differentiate

between these two mirror image compounds

and it turns out that's not so easy in

fact it requires really expensive

instruments and requires a pretty long

period of time

what's really also interesting about

this however if you take these same two

mirror images and give them to most

humans in this case this is a

picture of my daughter emma when she was

three years old

it turns out even a three-year-old child

can take these two compounds and

differentiate them instantly just by

smelling them they can smell the

difference between these two compounds

now you may be wondering why is that

well that happens because biology human

biology is made up of building blocks

which are one mirror image but not the

other one

so for example proteins dna

carbohydrates hormones all these

building blocks of life are made up of

one mirror image but not the other one

now it turns out that has lots of really

important biological implications

the easiest one to sort of talk about is

with respect to medicine

because it turns out well your hands can

exist as mirror image it turns out many

medicines also it can exist as mirror

images and it turns out your body can

typically recognize one of those mirror

images but the other mirror image can

often be problematic it can be toxic it

can be dangerous

now this is a hundred billion dollar

market for our economy and as such it's

extremely important that we can have

access to one of these mirror images of

the medicine but not the other one

and the way you can think about going

about doing that would obviously be

through catalysis and this therefore

becomes known as asymmetric catalysis or

the desire to make one mirror image

selectively without making the other one

okay so that's asymmetric so the third

part of this is organo what does organo

mean

and to explain this i'm going to take

you all the way back to 1996.

why 1996 we'll talk about in a few

moments but we're actually first of all

going to discuss what were the branches

of asymmetric catalysis back in 1996 it

turns out there was two major branches

the first branch was biocatalysis

biocatalysis is when you take enzymes

from your body or living systems and you

use those to make one mirror image in

preference to the other one

the second major branch is metal

catalysis metal catalysis is a man-made

area which uses metals to allow you to

make one mirror image selectively

now if you're wondering why 1996 well

1996 is where my part in the story

actually begins

in 1996 i was finishing off my phd

studies at uc irvine out in california

now over the last two months many people

have said to me you must feel extremely

lucky extremely fortunate to have won a

nobel prize

and i tell them well i actually already

feel extremely lucky and fortunate

because i got to do my ph study phd

studies out in california at uc irvine

this was a really wonderful fantastic

time for me

and during that time i was also

extremely fortunate that i got to work

for this individual

this is professor larry overman he's

just a fantastic chemist he's an amazing

mentor but he's also really just a

superb human being

upon completing my phd studies i moved

back across america went to boston to to

harvard and i went to harvard to work

for professor david evans

david evans is a genius he's one of the

most influential chemists that's existed

and he's someone who is an absolute

master in the area of asymmetric

catalysis

and i moved to dave's lab to work in

this area and during that time i worked

on looking at metals to make single

mirror energy compounds

now these are some of the metals that

dave's group actually worked on and

during that time i learned an enormous

amount from dave and from his team but

every single day i was in dave's lab i

worked in this contraption this

contraption is known as a glove box this

glove box is designed to exclude air

it's designed to exclude oxygen it's

designed to exclude moisture

and every single day i would be in there

i'd be working away for many many hours

and after about two years of working in

a glove box i started to think to myself

why are we spending so much time in a

glove box every day

to understand that you have to think

about the metal catalyst themselves

so here is your typical metal catalyst

you can actually break it down into two

components the left hand side the right

hand side is shown here

the right hand side is the metal

if you think about these metals it turns

out metals in some cases but not in all

cases they can be expensive they can be

toxic they can be really difficult to

work with they often have problems being

out in the atmosphere which is why you

have to use glove boxes and in other

cases they're not sustainable

what's really interesting however if you

look at the other part of the catalyst

this is the organic component

organic molecules are often inexpensive

they're safe they're sustainable they're

recyclable

and at that time i started to think well

why don't we just simply use the organic

part as the catalyst and miss out using

the metal

now that was something that eventually

became known as organocatalysis

okay so in 1998 the end of my studies at

harvard i was really fortunate i landed

a job as an assistant professor at

berkeley

but before i got to berkeley i stopped

off at caltech to give a lecture and

while i was there i met with professor

eric

herrera and while i was there professor

carrera took me to dinner and gave me to

what is till this day one of the best

pieces of advice that anyone ever gave

me

he basically said the following

he said when you get to berkeley you're

going to be surrounded by some of the

best graduate students in the world and

you have to assume that whatever problem

you work on those students will help you

solve that problem regardless of whether

you have a solution to it already or not

and as such you should work on the one

which is of the highest impact you can

think of

so with this in mind i knew what i was

going to work on i was going to work on

organocatalysis

i knew that because of these advantages

we knew we could make them from nature's

building blocks we knew that these

molecules should not be sensitive to air

or moisture they should be inexpensive

these same types of catalysts should be

easy to handle you wouldn't have to use

a glove box because they can exist

happily out in our environment then

lastly they should be sustainable they

should be recyclable and they're

non-toxic

but this was not the main reason i was

interested in doing organo catalysis the

part that i was interested in was the

following idea

instead of trying to develop one or

catalyst organo catalyst that would work

for one transformation i was really

interested in the idea could we develop

an organo catalyst that could work for

hundreds of different reactions and

maybe this could become a field of

asymmetric catalysis

now that in and of itself was a pretty

grandiose idea the only problem is i had

absolutely no idea how to do it but

that's okay because eric carrera told me

it'd be fine i'd have great graduate

students they would help me solve this

problem

okay so in 1998 off i went to berkeley

started my research group and this is

one of my first photographs of that

group

i really love this photograph it's taken

at 10 past 10 on a friday night you can

see this young group in there doing

research trying to have an impact

and during that time one of the graduate

students in the group by the name of

tristan lambert tristan is now a very

successful professor over at cornell

university but back as a first year

graduate student he asked me a very

simple question

he said what is the mechanism of

reductive ammunition and i was a new

professor i was all excited to answer

this i ran to the board and i wrote well

we take a carbonyl you take an amine and

it reversibly forms an amino iron

and it's only when it's the amenia mine

does it have the electronic

configuration that it's reactive enough

to do the subsequent chemistry

and right there right then is when i had

my eureka moment

because i suddenly realized you could

use this idea for organocatalysis

more specifically you could take these

alphabet unsaturated carbonyls with the

means and reversibly form in many amines

and in many ways this should emulate a

field of catalysis and already been

successful using metals

now to sort of show this in a slightly

more conventional way if you think of

these two equations as shown in this

slide as being simultaneous the one on

the top is one that uses metals and it

turns out there's hundreds of reactions

that have been developed using that

concept

but the one at the bottom there was

basically no examples using organic

catalysts to do that but yet if these

were simultaneous equations they both

should be successful

and if that's the case then organo

catalyst should work for many different

types of transformations such as mukima

michael nitro and cycle additions the

less would go on and on and on of all

the possible reactions for

organocatalysis but at that time there

really weren't any

so we had to pick one of these one of

these we wanted to test it on

and what we chose was the diels-alder

reaction now the diels-alder reaction is

really famous to all chemists

it deservedly won the nobel prize in

1950 because it allowed you to take

relatively simple molecules and build

ring systems very much in a

straightforward fashion that could be

used in natural products that could be

used in medicines they could actually be

used in materials

we decided this reaction would be a

great platform or a great venue on which

to test our new organocatalysis concept

so we decided to use exactly that

so as shown here this is actually the

notebook page from kateria wren she was

a first year graduate student in my

group she was the first person in my

group to test this idea

and these are in fact the components of

a diels-alder reaction and you can see

in the middle above the arrow that would

be the organo catalyst

so we tested it we ran the reaction and

if we scroll all the way at the bottom

you'll see the result which is

highlighted it says not racemic

not racemic

that was unbelievably exciting to us not

receiving means it makes one mirror

image in preference to the other one

i was so excited when i saw this result

of an end to my office closed the door

jumped up and down for about five

minutes called my wife and said i think

we're going to get tenure we just got a

really really exciting result

but when my feet came back to ground i

walked back into the lab and i realized

that you can see the top of this slide

it says an initial result 48 ee

what does that mean well that meant in

terms of the meta remedies there was a

48 excess of one mirror image over the

other one

and for the chemistry community to take

this seriously that number actually has

to be about 90

so we had a decision to make did we want

to publish this or did we want to try

and go for a catalyst and go for the

gusto and get to 90

well we decided to do the latter and i

can tell you that was six of the most

nerve-wracking months of my life but

during that time we eventually got to a

catalyst that we thought was interesting

this is what's called the imidazolenones

we're interested in metazoans really for

two major reasons the first one was

they're really inexpensive

if you look at these molecules they're

actually made from phenylalanine which

is a building block of life it's an

amino acid that's combined with acetone

acetone is actually paint stripper

but the other reason we really liked

them we thought if we put these together

and made a catalyst they should be good

been able to generate the production of

one mirror image in preference to the

other one

and when we tested that that's exactly

what happened we could now achieve 90

percent excesses of one and the other in

these deals all the reactions

so again this was an extremely exciting

day in lab and at this point we're now

we have to tell the world

as a young professor you now have to

write a manuscript and you really want

to sort of climb up to the highest

rooftop and shout this out as much as

possible how important you think this is

and in fact when i look back on my first

manuscript i can see i really felt that

in this opening paragraph

in this opening paragraph i first of all

talk about why i think this is going to

have potential impacts on society for

academia for industry and for the

economy

the second thing i did in this holding

paragraph i gave this whole idea a name

i called it organocatalysis

now you might wonder organocatalysis why

does it matter you gave something a name

what's in a name

but it turns out naming things is really

really important for example you can go

back to john jacobs brazilians a very

famous swedish chemist very famous

scientist and while he was a

tremendously successful researcher he

was also the person that came up with so

much vocabulary and so much terms that

allow our field to have basically an

identity at the present time

words such as catalysis proteins polymer

even organic versus inorganic

and the importance of terms have carried

forward even into the modern era for

example things such as machine learning

nanotechnology organocatalysis these are

umbrella terms which really allow you to

describe fields that allow them to gel

and grow beneath those different types

of areas

but the third part of this opening

paragraph of the or manuscript which i'm

most proud of is that we introduced the

concept of a generic activation mode

now you may wonder what is a generic

activation mode but that's really just

the idea of saying that this idea of

catalysis should work not for one

reaction but for many many chemical

reactions

so obviously we had to go off and test

that

so if you remember we've just performed

the diels-alder reaction was shown here

so now we're ready to test it in other

reactions when we try it and it goes bam

bam

nothing it comes to a screeching halt

and this is something that happens in

science quite often where you get proof

of concept using one catalyst but you

suddenly realize it's not going to take

you all the different directions you

want to go in

so now we have to go off and design a

second generation catalyst

now with this in mind i was very

fortunate to have really two fantastic

young graduate students in my group by

the name of joel austin and chris barts

and what they did was they performed

molecular engineering on this first

catalyst they effectively took away two

carbons and then they introduced four

carbons in a different shape this was

sort of precision

engineering to try and describe this to

non-chemists that don't or to put it in

another context

one way i thought i could do this is to

talk about for example this footballing

god zlatan ibrahimovic who is someone

who is a precision footballer who does

precise things and achieves really

fantastic outcomes

one example of this is this goal he

scores where you can see here he does an

overhead kick

from almost 40 yards out to score this

goal

now okay he wasn't playing against a

team that was particularly good but the

point here is he performs a precision

technique to score a beautiful outcome a

really beautiful goal and we were

interested could we do the same with our

catalyst

so we set out to test this this was our

first generation catalyst we had three

reactions we now moved to a second

generation catalyst as shown here and

now we're off to the races things really

start taking off like gangbusters

at this stage we're also very fortunate

that carl anker jorgensen and hayashi

introduced another family of catalysts

which were also really valuable for

minimum catalysis and again completely

expanded this area

all right now at this point what we've

introduced is a minimum catalysis and

basically at the same time there was all

this beautiful work coming from ben

lester and carlos barbus really

expanding beautifully enemy catalysis

but i don't want to give you the

impression we were the only people who

were doing this in fact we certainly

weren't even the first ones to do it

there was many other people who were

sort of working in this area and i want

you to point those out

for phase transfer catalysis there was

doling ligo marioka and o'donnell in

lewis-base catalysis there was denmark

azeki and windberg in terms of

nucleophilic catalysis there was foo and

vedas in terms of peptide and partial

peptide synthesis was kelowna inuit

julia and miller

in carbine catalysis was ender's leaper

and tom rovas and in terms of hydrogen

bonding catalysis was corey and jacobson

and ketone catalysis there were sheet

and yang and one part i want to mention

which i think is absolutely critical if

it wasn't for the contributions of all

these people this field simply would not

exist and i certainly wouldn't be

standing here right now giving this

speech

okay so at this stage we started to

think about what other directions we

could take organo catalysis into

and one thing we thought of was wouldn't

it be interesting if you could take

imenium and enamine catalysis and put

them in the same vessel and you might

wonder why on earth would you want to do

that well it turns out we were

interested in emulating the way that

nature makes molecules it turns out what

nature does nature actually takes

enzymes in a biochemical assembly line

and in multiple catalytic reactions

takes simple molecules and makes very

complex ones

we started to ask could we do exactly

the same thing but instead of using

enzymes could we actually use small

organic molecules to do exactly the same

catalytic cascades

so in this context we took a relatively

simple molecule as the one shown in the

top left here and we put it through

these three catalytic cycles that all

sequentially fed into each other to

generate the molecule which is shown in

the bottom right hand side of the slide

now that molecule is much more complex

than the one in the top left and the

reason it's so much more complex is

we're trying to make the molecule shown

in this slide which is called strychnine

now you've probably heard of the word

strychnine before it's actually a very

dangerous molecule it's actually a

poison it's really a rat poison and you

may wonder why and if we're trying to

make rat poison

well it turns out this rat poison

stricken is actually a molecular

benchmark that people in the field of

total sentences use from which to

benchmark their technologies against and

using this cascade catalysis we were

able to in fact make it in a very rapid

12 steps

now other ways we started to think about

ways we could do exciting and new things

with organocatalysis was the idea could

be merged with other types of reactivity

the next type of reactivity we became

interested in was organic radicals

so this is moses gomberg he was the

person who discovered radicals in 1901

and has this really wonderful statement

in his manuscript which says this work

will be continued and i wish to reserve

the fuel for myself

well clearly that did not happen all of

the chemistry world started to use

radicals and the reason was because as

the name suggests radicals allow you to

do radical things they allow you to

achieve radical reactivity

and so we became really interested in

could you merge this with

organocatalysis

so this was actually work that was

conceived of and executed on by a really

fantastic graduate student in my group

by a name of theresa beeson

what teresa did was she said i should be

able to make these same enamines but

instead of using these enamines to do

chemistry what if we actually plucked an

electron out to change its reactivity

now that it's a radical this radical

should allow you to do many many

different new types of chemical

reactions and that turned out to be

exactly the case we published many new

types of processes using what's called

this somo catalysis

but this actually became a stepping

stone for us to think about could we

actually take radicals and

organocatalysis and make it even more

sustainable in terms of how you'd

actually perform these transformations

in this context we became really excited

about the fact of being able to sort of

harness visible light with

organocatalysis

now harnessing visible light is

something that inorganic chemists have

been working on for almost three decades

and the idea here was to try and harness

the the light that would come from the

sun and use that as energy to power the

planet

we became interested in the idea could

we take that knowledge that they had

developed but now transport it into the

organic world and once it was in the

organic world start to think about doing

a thing called photoreducts catalysis

this would allow us to make new bonds

this would allow us to perform new types

of transformations that could have a

whole variety of different applications

now it turns out this was actually work

that was performed in collaboration with

a wonderful postdoc in my group by the

name of dave nisevich

this is basically what we were

attempting is shown in this slide we're

taking light bulbs we're taking organo

catalysis and then at the right moment

we switch simply switch on the light we

switch on the blue led

and new chemistry starts to happen

now what's really exciting about photo

radars is that it became a field in and

of itself actually became a field as as

large as organocatalysis and that's

something that we're very much proud to

be a part of

now in terms of thinking about this the

part that's really exciting is we've

been really lucky as a group to be

involved with organocatalysis

and we've also been really lucky to be

involved with this field of photo radox

catalysis but it's been really exciting

to see that organocatalysis effectively

created this bridge at least in our lab

into photo radar catalysis in fact if

you think about it it really was a

catalyst that allowed for a redox

catalysis field to come together again

at least in our lab

okay so at this point another question

that a lot of people ask me what about

applications of organocatalysis and i'm

going to show you just a few

the first one is in the area of

fragrances perfumes

it turns out perfumes are used on an

enormous scale across the world every

single day

in pharmanish this company that's in

switzerland and geneva are very

successful at performing and producing

many of these different perfumes and one

of the ones which is actually shown here

is produced by combining organocatalysis

with photoreaders this actually makes

lily of the valley

tons of firminess also in northern india

make 300 metric tons of this beautiful

rose smelling perfume also using

organocatalysis

okay so that's perfumes what other areas

can use organocatalysis for well you can

actually use it in terms of materials

and actually for the recyclable plastic

economy this is some very important work

that's been conducted by bob weymouth

and james hedrick and many of you

probably know that plastics are

polluting our oceans

and what bob and james are doing is

they're using organocatalysis to

effectively break down polymers back

down to monomers which can then be used

again to remake polymers making polymers

and plastics completely recyclable and

completely sustainable which is

obviously extremely important

but the area in which organocatalysis is

probably most heavily used is that

towards making medicines or developing

medicines

i'm just going to show you one example

this is tulsa japan it's actually used

to treat chronic migraines

this particular molecule this particular

medicine is actually made and it's made

using organocatalysis and in fact it

uses the immune catalysis i talked about

the beginning of my talk to make one of

the mirror images in preference to the

other one

but the last thing i want to talk about

with respect to the value of

organocatalysis is this slide which is

shown here we call this democratizing

catalysis now this is an aspect of

organic catalysis i certainly did not

see coming but i think it may be one of

the most important aspects of

organocatalysis

and it is that organic catalysis is

extremely affordable and a cheap and

accessible feel to the whole world

and this means if you go across every

continent that exists in the world right

now people are being educated about

organocatalysis using these different

systems

they're so inexpensive to the point that

it's really straightforward for people

not just to learn about using them but

actually to do their own research

so when i think about where the next big

idea in organo catalysis is going to

come from

i realize it's not going to be about

resources it's not going to be about

funding

it's going about who in the world has

the best idea regardless of which

country they come from

okay now people often ask me what does

the future hold for organocatalysis and

to be honest with you i really don't

have an answer to that question

but what i do know is that we have to

provide for our ever expanding global

population in a responsible way and that

includes catalysis catalysis has to be

sustainable as we go forward

so clearly this will involve using

organocatalysis and biocatalysis will

also include things like photocatalysis

and electrocatalysis it's going to be

essential that we move to these types of

catalysis if we're going to create

sustainable technologies for our planet

okay so that's my last chemistry slide i

want to finish off by thanking the

people who first of all did this work i

talked about the people already from

berkeley we moved to caltech where we

actually did most of organo catalysis

research and i want to thank all the

people who are sort of shown on this

slide here this was a fantastic group to

work with and i also want to thank also

all my friends and the faculty members

out at caltech

in 2006 we actually moved over to

princeton we continued our organic

catalysis work and also we started doing

lots of photo redox as well and again i

have to thank these phenomenal groups

these phenomenal teams i was lucky to

work with during that time frame

in terms of other people i have to thank

i have to thank this woman this is my

wife jean she's a love of my life she is

an amazing person she's an amazing

chemist she's an amazing mother but more

than anything she's my best friend and

this journey honestly would not have

been the same without her being there so

i have to thank her so much

i also have to thank my family this is

danielle this is lauren this is emma

this is us having a boogie on the

harbour bridge in sydney which was a lot

of fun that day and i also have to thank

julie julie is my unique and wonderful

mother-in-law who's been an amazing

supporter through all of our times as we

went all through all these different

stages of our life

in terms of other people i have to thank

i have to thank my siblings ian and

lorraine

many people have heard this story that i

would not have went to university if it

wasn't for my brother going there first

but i think people haven't heard the

story that i wouldn't have survived the

university if it wasn't for my sister

lorraine so i just want to say them i

love you both and i can't wait to

celebrate with both of you

other people i have to thank have to

thank educators that basically first of

all the educators all over scotland who

work very tirelessly to take people like

me and try to put them in a better spot

i have to thank the teachers at the

stevenson primary bestseller academy and

i have to thank the faculty and staff at

the university of glasgow and again

without these people i certainly

wouldn't be standing on this stage

the last part um is i want to dedicate

this talk and i want to dedicate this

talk to three people who are not here

the the first person i want to dedicate

this to i've already mentioned and

that's carlos barbus

carlos was a pioneer of organocatalysis

he was right there at the beginning with

myself and ben

unfortunately he was taken away from us

too early in

2014 and over the last two months i

think about carlos every single day

and it would have been so wonderful if

carlos had been here to celebrate this

with both myself and ben

the last people i want to dedicate this

to are my mom and dad um

this is a very difficult thing for me

but basically someone recently said to

me how would your mom and dad felt about

this would they have been proud would

they be proud of you winning this prize

and i said that i don't have the words i

can't articulate

how how proud they would be i just can't

get there

but the one thing i can tell you is a

seven-year-old boy in scotland there's

no way i could imagine i'd be standing

on this stage giving this speech but i

think my mom and dad could have because

they were unbelievably supportive and

they believed that myself and my family

we could go absolutely anywhere and for

that i'm incredibly grateful

with that i want to thank you for your

attention thanks a lot

you