These slides are part of a talk to school teachers. They were designed to showcase some of the applications of organic chemistry, the range of natural and synthetic products. I'm not sure how much use it is without my commentary but, as always, it seems a waste to leave it on my hard drive. The second half gave a overview of chirality and stereoisomers as this topic often causes problems with students. This second half owes a lot to an excellent paper by Robert Gawley (J. Chem. Ed. 2005, 82, 1009) and just has prettier papers. This version of the talk includes a section I removed when presenting (due to time) on artificial sweeteners.

1. ORGANICchemistry
Massey University
Gareth Rowlands
1Wednesday, 18 November 15

2. relevance stereoisomers
ORGANICchemistry
2Wednesday, 18 November 15

3. !" "#$%r&
(Z)-3-hexenal
fr&'()* +%$ ,r#''
©P#w&)_M@-!+.r
O
3Wednesday, 18 November 15

4. ©/&$#-.)!+.'@-!+.r
linalool
3,7-dimethylocta-1,6-dien-3-ol
'/&)) 0f )!)!&'
HO
4Wednesday, 18 November 15

5. ©T0"#)L%/!"1!$*@-!+.r
OH
menthol
(1R,2S,5R)-2-isopropyl-5-methylcyclohexanol
$#'$& #"2 '/&)) 0f /!"$
5Wednesday, 18 November 15

6. P
P
Rh
Ph
Ph
Ph
Ph
N
Et
Et
isomerisation N
Et
Et
hydrolysis
O
OH OH
addition
reduction isomerisation
H
Natural or man-made?
3000 tons per year
+0%,( /&2!+!"&, 2&+0",&'$#"$', #3&r'(#v&, $00$(p#'$& &$+
6Wednesday, 18 November 15

7. R
C
OH
O
Too many
r&#+$!0"'
carboxylic
acid
alcohol
R OH
alkene
C C
R4
R1 R2
R3
haloalkane
R X
4!2#$!0"
r&2%+$!0"
'%5$!$%$!0"
#22!$!0"
&)!/!"#$!0"
#22!$!0"
&)!/!"#$!0"
7Wednesday, 18 November 15

8. Fundamental
Pr!"+!p)&'
R
C
O
O
H
O
H
R
C
O
O
H
O
H
H
H
+ +
C#rb4*)!+ #+!2
P(1p(0r!+ #+!2
O
P
OO
O
R1
R2
H H
O
H
H
O
H
H
+ +
O
P
OO
O
R1
R2
S%)f0"!+ #+!2
R
S
O O
O
H H
O
H
H
O
H
H
+ +
R
S
O O
O
8Wednesday, 18 November 15

9. Br0/!"#$!0"
R1
C C
R2H
H
C C
Br
H
R1 H
R2
Br
BrR1
H
R2
H
Ep4!2#$!0"/'%5$!$%$!0"
C C
O
H
R1 H
R2
R1
C C
R2H
H
HO
OHR1
H
R2
H
D!(*2r4*)#$!0"
R1
C C
R2H
H
HO
R1
H
OH
H
R2
9Wednesday, 18 November 15

10. (R)-muscone
(R) = 61 ppb & (S) = 223 ppm
(R) r!+( /%'.* '/&)) ($>,0)2)
©b#b00"™@-!+.r
O
10Wednesday, 18 November 15

11. O
O
O
O
addition
reduction
ring-cl#ing
metathesis
no commercial route to pure optical isomer
'*"$(&$!+ /%'. !' r#+&/!+
Natural or man-made?
Ru
Cy3P
PCy3Cl
Cl
Ph
11Wednesday, 18 November 15

12. O
OH
O
vanillin
1,800 $0"' !'0)#$&2 p&r *&#r
>12,000 $0"' +0"'%/&2 p&r *&#r
©(%pp6!&@-!+.r
12Wednesday, 18 November 15

13. vanillin
>10,000 $0"' '*"$(&'!'&2 p&r *&#r
Natural or man-made?
OH
O
O O
OH
addition
O
OH
HO
"idation
O
OH
O
OH
O
O
OH
elimination
O
OH
O
13Wednesday, 18 November 15

14. haem B
r&2 +0)0%r 0f b)002
N N
NN
CO2HHO2C
Fe
14Wednesday, 18 November 15

15. dye-sensitised solar cells
,r&&" 2*& $0 #50rb '%")!,($
N N
NN
Zn
Ph
Ph
NC
CO2H
Ph
Ph
©Or,&0"DOT@-!+.r
15Wednesday, 18 November 15

16. paclitaxel
!'0)#$&2 fr0/ p#+!7+ *&w $r&&
T80)™ %'&2 $0 $r&#$ +#"+&r
©J&r/&* B0#r2@F)!+.r
O
AcO
H
OH
OBz
OH
O
O
OH
Ph
BzHN
AcO O
AcO
16Wednesday, 18 November 15

17. semi-synthesis
0"& fr#,/&"$ /#"-/#2&
©Er!+ H%"$@-!+.r
Natural or man-made?
O
AcO
H
OPG
OBz
OH
AcO O
AcO
HO
O
AcO
H
OPG
OBz
OH
O
O
OH
Ph
BzHN
AcO O
AcO
N
PGO
O
O
amid!
formatio"
17Wednesday, 18 November 15

18. avermectin B1a
#"$!-p#r#'!$!+ ("&/#$02&' #"2 #r$(r0p02')
©S+0$ N&)'0"@-!+.r
O
O
O
H
O
H
O
H
O
HO
H
O
OH
H
O
O
O
OHO
18Wednesday, 18 November 15

19. Br0/!"#$!0"
R4
C
R1
C
R3
R2
+ Br2
additio!
Br
BrR4
R2
R1
R3
H*2r0,&"#$!0"
R4
C
R1
C
R3
R2
+ H2
additio!
H
R4
R1
H
R3
R2
Basic
r&#+$!0"'
hydrogenation
0"& 0f $(& /1$ !/p0r$#"$ !"2%'$r!#) r&#+$!0"'
19Wednesday, 18 November 15

20. ivermectin B1a semi-synthesis
%'&2 !" $(& 7,($ #,#!"'$ r!v&r b)!"2"&''
©W!.!C0//0"'
Natural or man-made?
O
O
O
H
O
H
O
H
O
HO
H
O
OH
H
O
O
O
OHO
20Wednesday, 18 November 15

21. Brincidofovir
$r&#$/&"$ f0r '/#))p4 #"2 %'&2 #,#!"'$ &b0)#
©NIAID@F)!+.r
Synthetic
N
N
NH2
O
O
OH
P
OO
HO
O
{
2&)!v&r*
{w#r(&#2
21Wednesday, 18 November 15

22. Substitutions
'#/& #' 2!'p)#+&/&"$ 0f (#)!2&' &$+
N
N
H
NHCOPh
O
OCPh3
O
substitution
N
N
NH2
O
OH
Ph3CO
substitution
TsO P
O
OEt
OEt
N
N
NH2
O
O
Ph3CO
P
O
OEt
OEt
pseudo
halide
Basic
r&#+$!0"'
22Wednesday, 18 November 15

23. pyrethrin
"#$%r#) !"'&+$!+!2& f0%"2 !" +(r*'#"$(&/%/
+!"&r#r!!f0)!%/
O
O
O
©M%'$#", J0&@-!+.r
23Wednesday, 18 November 15

24. Cl
Cl
O
O CN
O
Synthetic
©A/b&rBr00.&@-!+.r
cypermethrin
'*"$(&$!+ !"'&+$!+!2& f0%"2 !" R#!2™
24Wednesday, 18 November 15

25. ISOMERS
25Wednesday, 18 November 15

26. Constitutional
!'0/&r'
C4H8O
O O
HO
bp = 66°C bp = 80°C
(b%$$&r'+$0+(
& #+&$0"&)
bp = 121°C
26Wednesday, 18 November 15

27. O
OH
HO
HO
HO
OH
O
HO
HOHO
HO
O
HO
HO
O
OH
O
HO
HO
O OH
OHO
HO
O
OH
O
HO
HO O
OHO
HOOH OH
O
HO
Stereoisomers
2!#'$&r&0/&r'
starch
p0)*/&r 0fα-,)%+1&
27Wednesday, 18 November 15

28. cellulose
p0)*/&r 0fβ-,)%+1&
©K%/#r#v&)@-!+.r
Stereoisomers
2!#'$&r&0/&r'
O
HO
HO
HO
OH
OH
O
HO
HO
HO
OH
O
HO
HO
O
OH
O
HO
HO
O
OH
O
HO
HO
O
OH
O
HO
HO
O
OH
O
HO
HO
O
OH
OH
28Wednesday, 18 November 15

29. Stereoisomers
2!#'$&r&0/&r'
cis and trans isomers
#)$&r' '(#p& #"2 p0)#r!$*
trans
E
cis
Z
29Wednesday, 18 November 15

30. Stereoisomers
oleic acid
/p = 13°C (0)!v& 0!))
OH
O
2!#'$&r&0/&r'
30Wednesday, 18 November 15

31. Stereoisomers
elaidic acid
/p = 45°C
OH
O
2!#'$&r&0/&r'
31Wednesday, 18 November 15

32. OH
O
(not a) Stereoisomers
stearic acid
/p = 63°C (f0%"2 !" b%$$&r)
2!#'$&r&0/&r'
32Wednesday, 18 November 15

33. Stereoisomers
"#"0/0$0r
Me(ax)
Me(ax)
(3R,3'R)-(P,P)-trans
stable
Me(eq)
Me(eq)
(3R,3'R)-(M,M)-trans
unstable
(3R,3'R)-(M,M)-cis
unstable
Me(eq)
Me(eq)
(3R,3'R)-(P,P)-cis
stable
Me(ax)
Me(ax)
≥ 280 nm
≥ 380 nm
≥ 280 nm
≥ 380 nm
20°C60°C direction of
rotation
alkene isomerisation
33Wednesday, 18 November 15

34. Nanomotor to
/0v& 0b9&+$'
rotor
controls
direction
anchor
34Wednesday, 18 November 15

35. Nanomotor to
/0v& 0b9&+$'
x 8 real time
35Wednesday, 18 November 15

36. CHIRALITY
36Wednesday, 18 November 15

37. Chirality
!" 1 2!/&"'!0"
#+(!r#)
+(!r#)
J. C(&/. E2. 2005, 82, 1009
1 Dimension allows only translation
(no rotation)
37Wednesday, 18 November 15

38. Chirality
!" 1 2!/&"'!0"
#+(!r#)
+(!r#)
J. C(&/. E2. 2005, 82, 1009
1 Dimension allows only translation
(no rotation)
external
mirror point
internal
mirror point
38Wednesday, 18 November 15

39. Chirality
!" 2 2!/&"'!0"'
J. C(&/. E2. 2005, 82, 1009
2 Dimensions allows translation &
rotation (in plane)
#+(!r#)
external
mirror line
internal
mirror lines
39Wednesday, 18 November 15

40. Chirality
!" 2 2!/&"'!0"'
J. C(&/. E2. 2005, 82, 1009
2 Dimensions allows translation &
rotation (in plane)
#+(!r#)
external
mirror line
internal
mirror lines
+(!r#)
40Wednesday, 18 November 15

41. Chirality
!" 2 2!/&"'!0"'
Tetris™
:p)#!"' $(& !/p0r$#"+& 0f +(!r#)!$*
#+(!r#)
+(!r#)
41Wednesday, 18 November 15

42. Chirality
!" 2 2!/&"'!0"'
Tetris™
:p)#!"' $(& !/p0r$#"+& 0f +(!r#)!$*
#+(!r#)
+(!r#)
internal
mirror lines
42Wednesday, 18 November 15

43. Chirality
!" 2 2!/&"'!0"'
Tetris™
#+(!r#) + #+(!r#) = "0 pr0b)&/
#+(!r#)
#+(!r#)
43Wednesday, 18 November 15

44. Chirality
!" 2 2!/&"'!0"'
Tetris™
#+(!r#) + +(!r#) = "0 pr0b)&/
#+(!r#)
+(!r#)
44Wednesday, 18 November 15

45. Chirality
!" 2 2!/&"'!0"'
Tetris™
+(!r#) + +(!r#) = pr0b)&/
45Wednesday, 18 November 15

46. Chirality
!" 2 2!/&"'!0"'
Tetris™
+(!r#) + +(!r#) = "&&2 +0rr&+$ p!&+&
46Wednesday, 18 November 15

47. Chirality
!" 3 2!/&"'!0"'
#+(!r#)
+(!r#)
47Wednesday, 18 November 15

48. Chirality
!" 3 2!/&"'!0"'
#+(!r#)
+(!r#) external
mirror plane
internal
mirror plane
48Wednesday, 18 November 15

49. Chirality
!" 3 2!/&"'!0"'
#+(!r#)
+(!r#)
tetrahedral atoms
(+#rb0", p(1p(0r%' &$+)
49Wednesday, 18 November 15

50. CHIRAL
50Wednesday, 18 November 15

51. CHIRAL
51Wednesday, 18 November 15

52. p(0$0,r#p(: W!))! R0)f&'
CHIRAL
52Wednesday, 18 November 15

53. Why is chirality
!/p0r$#"$?
53Wednesday, 18 November 15

54. Why is chirality
!/p0r$#"$?
©C)1&_$0_(0/&@-!+.r
54Wednesday, 18 November 15

55. Why is chirality
!/p0r$#"$?
©C)1&_$0_(0/&@-!+.r
O
O
H3N H
O
O
NH3H
L-alanine
1.5 ; 'w&&$&r
$(#" '%+r1&
D-alanine
b!$$&r
55Wednesday, 18 November 15

56. Why is chirality
!/p0r$#"$?
©/#r7'75 & &'-2&-w&@-!+.r
(R)-carvone
'/&)) 0f
'p&#r/!"$
(S)-carvone
'/&)) 0f +#r#w#*
O
H
O
H
56Wednesday, 18 November 15

57. O
O
H3N H
O
O
NH3H
Why is chirality
!/p0r$#"$?
©NIAID@-!+.r
L-alanine
(%/#"'
D-alanine
b#+$&r!#) +&)) w#))
57Wednesday, 18 November 15

58. Why is chirality
!/p0r$#"$?
(S,S)-ethambutol
$%b&r+%)1$#$!+
(R,R)-ethambutol
+#%'&' b)!"2"&''
HO
NH
H
N
HO
OH
HN
H
N
OH
58Wednesday, 18 November 15

59. What is the problem with
+(!r#) /0)&+%)&'?
Identical 'p&+$r1+0p!+#))*
59Wednesday, 18 November 15

60. What is the problem with
+(!r#) /0)&+%)&'?
Identical p(*'!+#))*
60Wednesday, 18 November 15

61. Only separable if add
+(!r#)!$*
61Wednesday, 18 November 15

62. N
H
H
O
N3
CO2CH3
O
OH
Cl
N
H
H
O
N3
H3CO2C
O
OH
Cl
OH
OCH3
N
H
H
CO2CH3
O
O
Cl
CH3O
O
N3 N
H
H
H3CO2C
O
O
Cl
OCH3
O
N3
Only separable if add
+(!r#)!$*
towards Norvasc™
(6&r$&"'!0"
62Wednesday, 18 November 15

63. N
H
O
HN
N
H
O
NH
HO2C
OBzBzO
CO2
N
H
O
NH2
precipitate
HO2C
OBzBzO
CO2H
Only separable if add
+(!r#)!$*
towards ropivacaine™
)0+#) #"#&'$(&$!+
63Wednesday, 18 November 15

64. epothilones
#"$!-+#r+!"0,&"
O
O OH O
S
N
OH
O
64Wednesday, 18 November 15

65. Start from a chiral molecule
+(!r#) p00)
O
O
HO
(–)-pantolacton!
O O O
O
O OH O
S
N
OH
O
65Wednesday, 18 November 15

66. Temporary addition of chirality
+(!r#) #<!)!#r*
NHO
O
O
Cl
OTBS
( )3
amid!
formatio" O
O O
N
OTBS
( )3
su#titutio"
O
O O
N
OTBS
( )3
O
OTBS
( )3
O
O OH O
S
N
OH
O
66Wednesday, 18 November 15

67. External control
+(!r#) r&#,&"$
BnO OTES
O
B
O
O
CO2iPr
CO2iPr
BnO OTES OH
O
O OH O
S
N
OH
O
67Wednesday, 18 November 15

68. chiral
product
chiral
catalyst
substrate
(achiral)
chiral
catalyst
chiral
catalyst
substrate
(achiral)
chiral
product
External control
+(!r#) +#$#)*'!'
68Wednesday, 18 November 15

69. ©J#+.#)1@-!+.r
(R)-fluoxetine (Prozac™)
&p4!2#$!0" (4!2#$!0"/#22!$!0")
O
NH•HCl
CF3
69Wednesday, 18 November 15

70. Hydrogenation (reduction)
+(!r#) +#$#)*'!'
Ph
O
Me2N
SM : catalyst
10,000 : 1
H2
96%
97.5%ee
Ph
Me2N
H OH
Ar2
P
P
Ar2
Ru
Cl
Cl
N
H2
H2
N
iPr
H
OMe
OMe
Ar = 3,5-Me2C6H3
70Wednesday, 18 November 15

71. Ph OH
Ti(OiPr)4
(+)-DIPT
TBHP
89%
>98%ee
Ph OH
O
Ph NHMe
O
CF3
O
OH
TBHP
iPrO2C
CO2iPr
OH
OH
(+)-DIPT
Epoxidation (oxidation/addition)
+(!r#) +#$#)*'!'
71Wednesday, 18 November 15

72. Solvaldi™
'0f1b=!r
Hepatitis C treatment
$10.28 b!))!0" (US) !" 2014
O
HO F
N
O
NH
O
OP
NH
O
O
O O
72Wednesday, 18 November 15

73. Theend 73Wednesday, 18 November 15

74. The directors cut
74Wednesday, 18 November 15

75. Chemistry title
!" "#$%r&
cyanidin-3,5-O-diglucoside
r&2 +0)0%r f0%"2 !" )&#v&' #"2 w!"& ©90("2&,r&&@-!+.r
O
O
O
OH
O
OHO
HO
OH OH
HO
OH
OH
HO
OH
OH
75Wednesday, 18 November 15

76. O
O
OH
OH
O
HO
HO
OH OH
HO
OH
Chemistry title
!" "#$%r&
cyanidin-3-O-glucoside
b)%& +0)0%r f0%"2 !" b)#+.+%rr#"$ ©R!+(#r2 S$&bb!",@-!+.r
76Wednesday, 18 November 15

77. Chemistry title
"#$%r#) 0r /#"-/#2&
©NIAID@F)!+.r
linezolid (Zyvox)
'*"$(&$!+ #"$!b!0$!+ f0r 2r%, r&'!'$#"$ b#+$&r!#
ON
O
N
H
O
N
O F
77Wednesday, 18 November 15

78. Chemistry title
b#'!+ r&#+$!0"'
Substitutions
'#/& #' 2!'p)#+&/&"$ 0f (#)!2&' &$+
Cl
O
NH4OH
substitution
Cl
OH
NH2
O
Cl
condensation
Cl
OH
N
Ar
N
H
N
O F
O
O
Ph
substitution
N
N
O F
O
O
Ph
OH
N Ar
esterification
substitution
ON
O
N
N
O F
Ar
78Wednesday, 18 November 15

79. ©.#!b#r#87@-!+.r
Accidents will happen
#r$!7+!#) 'w&&$"&r'
O
O
HO
HO
HO
HO
O
OH
OH
OHOH
NH
S
O
O O
N
H
S
O Na
O O
sucrose
'%,#r
saccharin
(300-400;)
cyclamate
(30-50;)
79Wednesday, 18 November 15

80. Saccharin was accidentally discovered in 1879
when Constantin Fahlberg spilt some on his hand
before touching his mouth.
All values refer to how many times sweeter than
sucrose a molecule is.
Walters, D. E. The Rational Discovery of Sweeteners. In Sweeteners/Discovery, Molecular Design, and
Chemoreception; ACS Symposium Series 450; American Chemical Society: Washington, DC, 1990; pp 1-2
80Wednesday, 18 November 15

81. Accidents will happen
#r$!7+!#) 'w&&$"&r'
aspartame
(200;)
sucralose
(320-1000;)
O
O
H
N
O
NH3
O
O
Ph O
HO
Cl
OH
OH
O
O
OH
OHCl
Cl
81Wednesday, 18 November 15

82. Aspartame discovered in 1965 when James
Schlatter licked his fingers to try an pick up some
weigh paper. He was making peptides to assess
their anti-ulcer efficacy.
Sucralose was discovered in 1976 when a
scientist (Phadnis) thought his colleague has
asked him to taste the molecule (he actually told
him to test the compound).
Walters, D. E. The Rational Discovery of Sweeteners. In Sweeteners/Discovery, Molecular Design, and
Chemoreception; ACS Symposium Series 450; American Chemical Society: Washington, DC, 1990; pp 1-2
82Wednesday, 18 November 15

83. Accidents will happen
#r$!7+!#) 'w&&$"&r'
N
H
S
O Na
O O
N
H
S
O NH4
O O
N
H
S
OH
O O
N
S
O Na
O O
N
H
S
O Na
O O
N
H
S
O Na
O O
sweet 50% sweetness sour
flavourless sweet
aftertaste
salty or
bitter
83Wednesday, 18 November 15

84. Cyclamate discovered in 1937 during research
aimed towards anti-fever treatments. Graduate
student Michael Sveda put his cigarette on the
lab bench and when he came to smoke it found it
was very sweet.
Walters, D. E. The Rational Discovery of Sweeteners. In Sweeteners/Discovery, Molecular Design, and
Chemoreception; ACS Symposium Series 450; American Chemical Society: Washington, DC, 1990; pp 1-2
Small changes in structure can have a profound
impact on taste.
J. Org. Chem. 1944, 9, 89
84Wednesday, 18 November 15

85. ©.#!b#r#87@-!+.r
Accidents will happen
#r$!7+!#) 'w&&$"&r'
aspartame
(200;)
neotame
(11,000;)
O
O
H
N
O
NH3
O
O
Ph O
O
H
N
O
NH2
O
O
Ph
85Wednesday, 18 November 15

86. Apparently hydrophobic groups increase the
sweetner potency while blocking the nitrogen
slows degradation both during storage and in the
body.
Polanski, J. et al. Molecular Design and the Development of New Sweeteners. In Optimising Sweet Taste in
Foods; Spillane, W. J., Ed.; CRC Press: Boca Raton; 2006; pp. 307-326.
C&EN. 2014, 92, 11
H2N
H
NN CO2
NC
O
O
Lugduname
sweetest sweetener
220,000 - 300,000 x sucrose
not approved for consumption yet
86Wednesday, 18 November 15

87. Stereoisomers
The Visual Cascade
N
H
rhodopsin
N
rhodopsin
H
ligh!
2!#'$&r&0/&r'
87Wednesday, 18 November 15

88. N
rhodopsin
H
N
H
rhodopsin
O
OH
O R
O
OH
O
isomerisatio!
hydrolysi"
reductio!
esterificatio!isomerisatio!
hydrolysi"
#idatio!
condensatio!
88Wednesday, 18 November 15