Synthetic Chemistry Research Interest Group

1. Synthesis Research at the Department of Chemistry
29th
September 2016 Chemistry Networks Event
DEPARTMENT OF
CHEMISTRY

2. Research areas in Synthesis at Cambridge
Complex molecule synthesis Catalysis & new synthetic methods
O
O
O
O
R
R
Me N
Me
H
Me H
MeH
Pd
Pd MeN
Me
H
Me
H
MeO
O
R
H
Me N
Me
H
Me H
MeH
OO
O R
Pd
O
O
O
R
R
Me N
Me
H
Me H
MeH
O
C
O
Me
N
Me
Me
H
Me
H
O
O
R
Pd
O
N
Me
Me
Me
H
H
N
O
Me
Me
Me
Me
N
Me
H
Me H
Me
H
Pd
O
O
Pd(O2CR)2
CO
BQ
Cu(OAc)2
Me
Me N
H
Me
Me
N
Me
O
Me
Me
C–H activation
Cu-catalysis
enantioselective catalysis
ion-pairing catalysis
Computational chemistry
Physical Organic (supramolecular) Synthetic chemical biology
S
Me
N2
OEt
Oprotein functionalization
diversity oriented synthesis
medicinal chemistry
New technology
continuous flow synthesis
automation
high throughout synthesis

3. The Synthesis Research Group – people
Leeper (B)
Scherman (M)
Bernardes (B)
Nitsczke (M)
Barker (B)
Balasubramanian (B)
Abell (B)
Wright (M)
Whaetley (M)
Reisner (M)
Affiliated members
Boss (I)
Galloway (O)
Nolan (O)
Longbottom (O)
Teaching Fellows
Gaunt (O)
RIG Chair
Ley (O)Spring (O) Paterson (O) Bampos (I) Goodman (O)Hunter (O)
HS Chair
Phipps (O)
Royal Society URF
Research Active Faculty

4. Synthesis Research – People & Infrastructure
74 PhD students
55 postdoctoral researchers
17 undergraduate researchers
8 groups located across 6 laboratories
outstanding organic technicians
world class equipment for analysis
international events vibrant seminar series
outstanding graduate
education
Yusuf Hamed Laboratory for Chemical
Synthesis & Catalysis (Gaunt group)

5. Synthesis of complex molecules
Polyketide synthesis (Paterson, Ley, Goodman)
N
O
Me
H
H
H
OH
H
OH
N
H
N
H
Me
H
N OH
O
NH
HO OSO3H
OH
HO
OH
N
N
H
O Me
HO
N N
N O
H
H H
Alkaloid synthesis (Gaunt, Ley)
Terpene synthesis
(Ley)
Macrolide synthesis
(Ley, Paterson)Peptide-related synthesis (Ley)

6. Catalysis and new reaction development
C–H activation (Gaunt)
O N
H
Pd
O
O
O
CH3H
O
CH3
TfO
I
Ar
Ar
L
Cu
X
TfO
LCu(I)X
(III)
(+)Ar
Ar
New reactivity (Gaunt)
NN
S Ir
BPin
BPinPinB
O
O O
N
R
H
Ion-pairing
catalysis (Phipps)
In all cases we believe that the selectivity observed reflects the
relative reactivity of the initial and first formed boronic acids
(Fig. 1b). In some cases, the intermediate boronic acid was observed
to be particularly unstable and prone to protodeboronation. For
example, in the case of the coupling between the diazo compound
and aryl boronic acids, we observed rapid addition of the diazo
species to the boronic acid partner but noted that some proto-
deboronation occurred even at room temperature. However, we
Me
87
41
56
74
69
65
Me 21
62
39
Me
5a5
5a6
5a7
5a8
5a1
5a2
5a4
5a9
5a3
OMe
5a
OMe
6a
R
Mono-addition
product
Double-addition
product
0.5 ml min–1
2a
OMe
1
Addition Trapping
1
2
3
4
5
6
7
8
9
1:0.08
1:0.40
1:0.35
1:0.20
1:1.50
1:0.60
1:0.20
1:0.16
–
Entry R Compound 5a:6a ratio Yield (%) Entry R Compound 5a:6a ratio Yield (%)
B(OH)2
R
Reaction conditions: 0.3 mmol of 2a (41 μl min–1
), 1.5 equiv. of 1, CH2Cl2, rt (30 min), then pinacol (overnight). Yields refer to the isolated mono-additon product based on the diazo species. Caution: diazo
compounds are unstable species so they should be handled on a small scale.
MeOMeO MeO
Protodeboronation
8a-d
R1
N2
R1
B
HO OH
B
OH
OH
H
3
R2
B
OHHO
4
2
R1
R2
R1
R2
B
7
R1
OH
OH
R3 R3
1
N N N
MeO O
R2
N2
H
2
R3
N2
H
2
New reactions as continuous flow processes (Ley)
Enantioselective catalysis
(Phipps, Gaunt, Goodman)

7. Computational organic chemistry (and informatics)
H
O
H
O
H2N
N
N
H
N
Me
O
O
H2N
N
N
H
N
Me
O
α β E
Solvation effects (Hunter)
Predictive modelling (Goodman)
Understanding synthetic reactions (Goodman)
C–H activation (Gaunt)
Asymmetric catalysis (Goodman)

8. Physical Organic and Supramolecular Chemistry
N
N
X
N
X
X
N
X
RO
RO
RO
RO
CHO
HN
RO
X
CHO
NO2
HO
X = H-bonding group
(OH or phosphine oxide)
N
N
N
O
O
N
O
RO
RO
RO
RO
H
H
H
N
N
N
N
OR
OR
OR
OR
O H
O
O
O
O
RO
NO2
OR
O2N
O
O
O
O
PO
R
R
PO
R
R
PO
R
R
PO
R
R
monomer
synthesis
oligomer
synthesis
duplex
formation
synthetic supramolecular chemistry for non-natural bio-polymers (Hunter)
host–guest chemistry (Nitschke, Bampos and Scherman)
curcubitril chemistry (Scherman)
porphyrin
chemistry
(Bampos)
cages (Nitschke)

9. Synthetic Chemical Biology
Membrane chemistry (Hunter)
All possible
compounds
Combinatorial library
(appendage &
stereochemical diversity)
DOS library
(skeletal, appendage
& stereochemical diversity)TOS
Combinatorial
Library
DOS
Library
Marketed
Drugs
HO
O S
Cl
N
N
H
N
NO2
N
H
N
NH2Et
EtO2C
Cl Cl
OH
Small molecule discovery (Spring)
Protein–Protein interactions (Spring, Hunter)
Diversity Oriented Synthesis (Spring)
Quorum Sensing (Spring)
S
Me
N2
OEt
O
Protein functionalization &
Bio-orthogonal chemistry
(Gaunt, Bernardes, Spring)

10. New Technology Platforms
Flow Chemistry (Ley, Lapkin, Gaunt)
‘Lab of the Future’
(Ley)
Alexei Lapkin
Chemical Eng.
Automated High Throughput Synthesis Platforms (Gaunt)
1536 well
reaction plates

11. Collaboration – academic and industrial
LABORATORY FOR
MOLECULAR BIOLOGY
DEPARTMENT OF CHEMICAL
ENGINEERING & BIOTECHNOLOGY
DEPARTMENT OF
CHEMISTRY
DEPARTMENT OF METALLURGY &
MATERIALS SCIENCE
multiple interactions with the Clinical School on the Biomedical Campus
PhD Program in Chemical Synthesis
10 year investment
currently have a 15 student cohort

12. Research areas in Synthesis at Cambridge
Complex molecule synthesis Catalysis & new synthetic methods Computational chemistry
Physical Organic (supramolecular) Synthetic chemical biology New technology
O
O
O
O
R
R
Me N
Me
H
Me H
MeH
Pd
Pd MeN
Me
H
Me
H
MeO
O
R
H
Me N
Me
H
Me H
MeH
OO
O R
Pd
O
O
O
R
R
Me N
Me
H
Me H
MeH
O
C
O
Me
N
Me
Me
H
Me
H
O
O
R
Pd
O
N
Me
Me
Me
H
H
N
O
Me
Me
Me
Me
N
Me
H
Me H
Me
H
Pd
O
O
Pd(O2CR)2
CO
BQ
Cu(OAc)2
Me
Me N
H
Me
Me
N
Me
O
Me
Me
C–H activation
Cu-catalysis
enantioselective catalysis
ion-pairing catalysis
S
Me
N2
OEt
Oprotein functionalization
diversity oriented synthesis
medicinal chemistry
continuous flow synthesis
automation
high throughout synthesis