Download 1 Only typical first year organic reactions are listed below, following

1 Only typical first year organic reactions are listed below, following simplistic rules (used in my course). Workup
means neutralize acid or base conditions to get a neutral product (could be acid or base). Real organic reactions can
often be ambiguous when all of the details are included (solvent, temperature, concentration, counter ions, catalysts,
etc.). Organic chemistry’s middle name is ‘ambiguous’ (Organic Ambiguous Chemistry). For your first time through
organic, I simplify some of that ambiguity by making reaction choices more clear cut than they might be if all factors
are considered. If you are learning from another instructor, who disagrees with my rules, or if you find the inevitable
errors, just change a reaction to suit your needs. These reactions are your working tools to synthesize more
complicated molecules. I have tried to include reagents for most of the 1C, 2C and 3C examples that we study. These
are your building blocks to 4C, 5C, 6C and larger organic molecules, many of which are listed after the 1C, 2C and 3C
examples. You should also be able to sketch out a plausible mechanism for each reaction. I left a few blank spaces in
case you or I need to add in any additional reactions. Unlike biochemistry, organic mostly uses simple monofunctional
molecules, so you don’t often have to worry about competing functional groups (called chemoselectivity). Your
choices are limited to the few reactions that are in our tool box. Try to have some fun as you make your own creations.
Please let me know when you find the errors. You will find alkene and alkyne reactions at the very end.
1C starting compound = CH4
1
2
Br2
h
CH4
3
Br
Br
H3C
H3C
5
H
1. NaOH
2. CH3Br
O
CH3
OH
SN2 at Me, 1o, 2o RX
Br
CH3
H3C
S
?
R
Br
CH3
1. n-BuLi
2. CH3Br
CH4
S
N
17
NaCN
SN2 at Me, 1o RX
15
CH4
1. n-BuLi
2. CH3Br
S
20
CH3
1. NaNR2
2. CH3Br
C
Br
S
NH2
H3C
12
Br
CH3
NaBD4
or
LiAlD4
D
CH3
'D' shows where the reactions occur
18
S
S
O
S
S
SN2 at Me, 1o, 2o RX
O
1. NaOH
2. CH3Br
3. NaOH
SN2 at Me, 1o, 2o RX
SN2 at Me, 1o, 2o RX
19
HgX2/H2O
NH
H3C
SN2 at Me, 1o, 2o RX
S
O
H3C
CH3
S
S
S
SN2 at Me, 1o, 2o RX
NH2
LiAlH4
SH
H3C
SN2 at Me, 1o, 2o RX
SN2 at Me, 1o, 2o RX
S
NaSH
H3C
9
1. NaN3
2. LiAlH4
3. workup
H3C
14
Br
NaBH4
Br
O
11
1. n-BuLi
2. CH3Br
always a base in our course
16
CH3
SN2 at Me, 1o, 2o RX
H
N
13
6
1. KH
2. CH3Br
O
SN2 at Me, 1o, 2o RX
R
SN2 at Me, 1 RX
SN2 only at Meo RX
8
10
o
O
7
1. NaOH
SH 2. CH3Br
O
SN2 at Me, 1 RX
O
O
1. NaH
2. CH3Br
H3C
o
free radical substitution
4
OH
OH
NaOH
HgX2/H2O
H
aldehydes
21
O
1. LDA,-78oC O
2. CH3Br
SN2 at Me, 1o, 2o RX
CH3
2 22
O
RO
23
1. LDA,-78oC O
2. CH3Br
CH3
RO
enolate = SN2 at Me, 1o, 2o RX
25
Ph
Ph
CH3Br
S
1. LDA,-78oC
2. CH3Br
H3C
C
26
27
CH3
Ph
S
Br
Ph
N
enolate = SN2 at Me, 1o, 2o RX
CH3
S
Ph
24
N
C
28
O
30
Ph
31
O
1. n-BuLi
2. H2C=O
S
Br
32
Ph
Ph
Ph
CH3Br
P
CH3
P
Ph
33
Ph
Br
Ph
CH2
H2C
Br
Ph
SN2 at Me, 1o, 2o RX
1. n-BuLi
2. H2C=O
CH3
P
Ph
Ph
1. n-BuLi
2. CH3CH=O
P
Br
Ph
CH3
PCC
aldehydes, 2o ROH
o
1 ROH
C
Br
Ph
OH
CH2
CH3
ketones
1 ROH
O
HN
O
CH3
46
O
H
TsOH
(-H2O)
NH2
H3C
make imines
O
H
O
O
o
O
O
O
O
H3C
NH2
O
CH3
N
H
The 1C side is more reactive (why?).
OH
Cl
H
H
H
O
O
O
H
O
O
O
OH
N
O
H
O
O
SH
S
H
o
3 amides
47
CH3
N
CH3
N
CH3 48
1. NaH3BCN
2. workup
HN
O
H
2o amines
HN
O
O
H
48
H
2 amines
C
H
SN2 at Me, 1 , 2 RX
47
O
H
o
ketones
45
C
1C product
is not stable
H
O
o
O
O
OH
OH
42
44
O
46
C
H
OH
O
1. NaOH
2.
Br
O
43
C
O
C
OH H
OH
Fischer ester syn.
H
39
O
SOCl2
P
OMe O
terminal alkynes
C
Jones
acids, 2o ROH
1. RO
2. CH3CHO
E alkene
H
o
1. n-BuLi
2. CH3CH=O
N2
MeO
O
CrO3
H2O
O
Br
Ph
O
41
TsOH
(-H2O)
O
H
Ph
1. n-BuLi
2. CH3CH=O
3. n-BuLi
4. workup
38
CrO3
py.
OH
40
P
Z alkene
37
CH3
P
36
Ph
Ph
Ph
Ph
35
34
Ph
O
S
29
Ph
CH3 1. n-BuLi
2. CH3CH=O
Ph Br
Ph
Br
Ph
SN2 at Me, 1o, 2o RX
1. n-BuLi
2. H2C=O
CH3
H
O
N
H
2o amines
3o amides
3 49
CH3
TsOH
(-H2O)
NH2
H3C
O
H
50
H
make imines
55
56
1. Mg or Li
2. H2C=O
3. workup
CH3
58
1. Mg or Li
2. O
Br
61
1. Mg or Li
2. O
CH3
3. workup
CH3
67
H
N
R
R
70
Br
1. only Li
2.
O
CH3
OH
3. workup
60
Br
1. Mg or Li
2. O
CH3
3. workup
CH3
68
OH
allylic alcohol
O
71
CH3
3. workup
Br
1. Li
2. CuBr
H3C
Cu
Li
cuprates
76
N
allylic alcohol
69
H3C
Cu
CH3
ketones
Li
77
HO
allylic alcohol
H3C
Cu
Li
cuprates
75
O
2. workup
conjugate addition
Cu
O
O
CH3
Li
cuprates
78
O
1.
H3C
OH
allylic alcohol
1.
Cu
2. workup
two RBr coupling
3o alcohol
CH3
CH3
cuprates
two RBr coupling
3. workup
CH3
Br
OH
1. Mg or Li
O
2.
Br
1.
OH
carboxyli acid
make LDA 3. workup
O
Li
O
R
R
H3C
74
2. workup
1. n-BuLi
2. O
H
HO
cuprates
CH3
Br
3. workup
72
CH3
1.
CH3
66
ketones
73
1. Mg or Li
2. O
2o alcohol
1. Mg or Li
2.
N
C
Br
Br
63
OH
1. n-BuLi
2. O
H
1. Mg or Li
2. O=C=O
3. workup
Br
3o alcohol
R
R
make LDA 3. workup
1. n-BuLi
2.
O
make LDA 3. workup
O
3. workup
3o alcohol
OH
N
3. workup
OH
3. workup
CH3
1. Mg or Li
2. O
CH3
OH
Br
2o alcohol
65
1. Mg or Li
2.
O
Br
OH
H
3. workup
62
1o alcohol
1. Mg or Li
2. O
57
1. Mg or Li
2. O
Br
OH
3o amines
54
CH3
2o alcohol
Br
64
2 amines
59
OH
H
O
3. workup
CH3
o
Br
OH
1o alcohol
N
2. NaH3BCN
3. workup
H
H
53
1. TsOH (-H2O)
H
N
O
HN
1. NaH3BCN
2. workup
N
52
Br
CH3
CH3
N
51
Cl
2. workup
ketones
4 79
80
1. Mg or Li
2.
O
Br
OH
OH
Br
HBr
82
83
Br
CH3
SN2 at Me, 1o RBr
SN1 at 2o, 3o RBr
85
1. NaBH4
2. workup
or
1. LiAlH4
2. workup
O
ketones too
CH3
86
OH
H
2 alcohol
OH
NH2
o
1 amines
OH
95
OH
C
D
C
R
H
H
O
o
Me, 1 alcohol
D
97
1. NaBD4
2. workup
O
or
OH
1. LiAlD4 D
2. workup
1o alcohol
epoxides too
O
H
TsOH (-H2O)
HO
OH
protect aldehydes and ketones
O
O
H
H
acetals
103
98
O
epoxides too
C
OH
1. NaBD4
2. workup
or
1. LiAlD4
2. workup
1o alcohol
O
O
acetals
CH3
H3O
H2O
D
OH
2o alcohol
C
D D
1. LiAlD4
2. workup
N
NH2
o
1 amines
nitriles too (x2)
2o alcohol
O
CH3
acetals
protect alcohols
O
O
H
H
acetals
H3O+
H2O
O
H
H
deprotect aldehydes and ketones
105
Zn / HCl
CH3
epoxides too
CH3
Me, 1o alcohol
99
O
O
OH
deprotect alcohols
1. NaBH4
2. workup
or
1. LiAlH4
2. workup
90
102
O
TsOH
OH
OH
101
OH
CH3
1. LiAlH4
2. workup
R
O
C
D
H
Me, 1o alcohol
D
Me alcohol
96
104
+
H
O
OH
1. LiAlD4
2. workup
CH3
only
O
Me, 1o alcohol
only
O
1. LiAlD4
2. workup
C
H
epoxides too
OH
87
CH3
1. NaBH4
2. workup
or
1. LiAlH4
2. workup
O
only
O
H
1. LiAlH4
2. workup
C
1. LiAlH4
2. workup
94
CH2
OH
only
O
o
nitriles too (x2)
100
CH3
89
C
1. NaBH4
2. workup
or
1. LiAlH4
2. workup
O
prevents rearrangement at 2o ROH
88
N
84
Br
CH3
CH3
CH3
SN2 at Me, 1o RBr
SN1 at 2o, 3o RBr
1. TsCl, py.
2. NaBr
OH
SOBr2
Br
PBr3
SN2 at Me, 1o RBr
SN1 at 2o, 3o RBr
3o alcohol
OH
OH
CH3
CH3
Cl
3. workup
CH3
81
H
H2
C
H
H
H
Clemmenson's reduction = acidic
O
H
H2NNH2
RO / 
H2
C
H
H
H
Wolff-Kishner reduction = basic
5 2C starting compound = CH3CH3
1
2
Br2
h
3
Br
H
O
K
Br
R
4
5
Br
Markovnikov
6
Br
1. BH3
2. Br2, CH3O
HBr
Br
Br
Br
Br
Br
11
1. 3 eqs.
NaNR2
2. O
Br
OH
C=O addition
NaOH
1. NaH
2.
OH
OH
SN2 at Me, 1
17
NaSH
SH
SH
SN2 at Me, 1o, 2o
19
O
NH
O
Other alkene and alkyne reactions
are provided in a chart below.
Br
O
1. NaOH
2.
Br
18
Br
S
Br
25
1. n-BuLi
2.
Br
NaCN
S
S
S
SN2 at Me, 1o, 2o
acetal
28
29
S
O
HgX2/H2O
S
ketal
ketone
NH2
C
rxn 2 = SN2 at Me, 1o
24
26
S
1. NaNR2
2.
Br
N
SN2 at Me, 1o, 2o
SN2 at Me, 1o, 2o
1. NaN3
2. LiAlH4
3. workup
O
SN2 at Me, 1o, 2o
21
NH2
O
OH
SN2 at Me, 1o, 2o
23
S
dithiane
1. NaOH
2.
Br
O
20
22
S
15
SN2 at Me, 1o, 2o
1. NaOH
2.
Br
3. NaOH
4. workup
rxn 2 = SN2 at Me, 1o
12
SN2 at Me, 1o
o
16
Br
HO
1. 3 eqs.
NaNR2
2.
Br
3. workup rxn 2 = SN2 at less
hindered C
Br
14
13
Br
Br
double E2
1. 3 eqs.
NaNR2
2. O
H
3. workup
9
1. 3 eqs.
NaNR2
2. workup
Br
free radical substitution (x2)
Br
anti-Markovnikov
8
Br
E2 at 1o, 2o, 3o
HBr
ROOR
h
anti-Markovnikov
2 eqs.
Br2
h
10
R
E2 at 1o, 2o, 3o
free radical substitution
7
1. n-BuLi
2.
Br
N
S
1. n-BuLi
2.
Br
SN2 at Me, 1o, 2o
27
S
O
HgX2/H2O
S
ketal
S
30
H
aldehydes
6 31
32
O
1. LDA,-78oC
2.
Br
O
rxn 2 = enolates = SN2 at Me, 1o, 2o
34
Ph
35
Ph
Ph
S
Br
S
o
SN2 at Me, 1 , 2
37
Ph
1. n-BuLi
2.
O
S
o
N 1. LDA,-78 C
2.
Br
C
N
C
H3C
rxn 2 = enolates = SN2 at Me, 1o, 2o
Ph
O
1. n-BuLi
2. H2C=O
Br
Ph
O
1. n-BuLi
2. CH3CH=O
S
Ph Br
makes epoxides
makes epoxides
38
39
41
42
O
Br
Ph
40
Ph
Ph
Br
Ph
P
Ph Br
phosphorus ylids
Ph
1. n-BuLi
2. H2C=O
Ph
Ph
P
P
Ph
Ph
SN2 at Me, 1o, 2o
43
P
Br
Ph
P
Ph
Ph
Z alkenes
46
OH
o
CrO3
py.
H
ketones
o
1 ROH
aldehydes, 2 ROH
49
TsOH
(-H2O)
O
Br
Br
Ph
45
1. n-BuLi
2. CH3CH=O
3. n-BuLi
4. workup
P
MeO
OH
1 ROH
o
acids, 2 ROH
H
OMe O
makes terminal alkynes
O
O
1. NaOH
2.
Br
O
OH
rxn 2 = SN2 at Me, 1o, 2o
OH
o
1. RO
O
2.
48
O
CrO3
H2 O
1. n-BuLi
2. CH3CH=O
Z alkenes
N2
O
ketones
50
51
O
OH
OH
Ph
E alkenes
47
O
P
makes alkenes
Ph
H
Ph
Br
44
1. n-BuLi
2. O
Ph
Ph
33
36
S
Ph Br
sulfur ylids
Ph
o
O
1. LDA,-78oC
2.
Br
RO
RO
rxn 2 = enolates = SN2 at Me, 1o, 2o
O
O
Fischer ester synthesis
52
SOCl2
O
O
Cl
Cl
H
N
O
58
O
Cu
SH
N
H
57
O
Cl
59
Cl
NH2
Cl
O
O
Cl
Li
O
O
O
56
O
N
O
O
OH
OH
55
54
O
53
O
O
O
OH
S
Cl
60
O
7 63
62
61
O
O
O
O
NH2
N
H
O
H
N
O
O
N
O
64
O
SH
S
1. TsOH (-H2O)
H
N
N
O
65
O
O
O
66
O
O
OH
O
O
67
TsOH
(-H2O)
NH2
O
68
69
N
H
N
H
70
71
Br
Br
1. Mg or Li
2. H2C=O
3. workup
1 alcohol
73
1. Mg or Li
Br 2. O
2 eqs.
H
O
3. workup
73
2 eqs.
2 eqs.
H
O
3. workup
76
Br
3. workup
79
Br
77
1. Mg or Li
2. O
OH
Br
1o alcohol
OH
Br
Br
1. only Li
2.
O
3o alcohol
1. Mg or Li
2. O=C=O
3. workup
Br
3o alcohol
78
1. Mg or Li
2. O
OH
1. Mg or Li
2. O
Br
2o alcohol
3. workup
1. Mg or Li
O
2.
81
1. Mg or Li
2.
N
C
O
Br
3. workup
ketones
83
O
84
OH
3. workup
86
85
Br
1. Li
2. CuBr
Cu
1.
Li
Li
cuprates
cuprates
1.
87
O
O
Cu
Cu
Li
2. workup
OH
O
OH
carboxyli acid
75
OH
3. workup
3. workup
82
1. Mg or Li
2. O=C=O
3. workup
Br
3. workup
80
1. Mg or Li
2.
O
75
OH
O
3. workup
2 alcohol
1. Mg or Li
2. O
3o alcohol
Br
o
3o amines
3. workup
1. Mg or Li
2. O
74
2 eqs.
Br
2o alcohol
O
3. workup
2 alcohol
OH
72
OH
Br
o
1. Mg or Li
Br 2. O
1. Mg or Li
2. O
1. Mg or Li
2. O
74
OH
2o amines
H
3. workup
OH
o
2. NaH3BCN
3. workup
H
H
make imines
O
1. NaH3BCN HN
2. workup
cuprates
Br
2. workup
O
OH
carboxyli acid
OH
3o alcohol
OH
C=O addition
8 88
1.
Br
Li
cuprates
92
OH
2. workup
OH
SN2 at Me, 1o RBr
SN1 at 2o, 3o RBr
96
95
Br
Br
SOBr2
SN2 at Me, 1o RBr
SN1 at 2o, 3o RBr
1. TsCl, py.
2. NaBr
OH
93
Br
PBr3
SN2 at Me, 1o RBr
SN1 at 2o, 3o RBr
O
Cl
3. workup
OH
Br
HBr
94
Cl
cuprates
OH
1. Mg or Li
Br 2.
O
Li
2. workup
90
O
Cu
Cu
91
89
1.
prevents rearrangement at 2o ROH
97
O
H
1. NaBH4
2. workup
or
1. LiAlH4
2. workup
99
98
OH
only
O
OH
101
100
C
N 1. LiAlH4
2. workup
1. NaBD4
2. workup
or
1. LiAlD4
2. workup
103
O
106
1. NaBD4
2. workup
or
1. LiAlD4
2. workup
O
106
NH2
O
O
D
107
O
D
1o alcohol
R 1. LiAlD4
2. workup
TsOH (-H2O)
HO
OH
D
108
OH
H
O
D
2o alcohol
108
O
TsOH
protect aldehydes and ketones
H3O
H2O
O
H3C
H
Clemmenson's reduction
H
H3C
Wolff-Kishner reduction
H3O+
H2O
O
H
H
H3C
Wolff-Kishner reduction
CH3
87
O
CH3
3o alcohol
H2NNH2
RO / 
CH3
86
H2NNH2
RO / 
D
111
deprotect alcohols
O
OH
deprotect aldehydes and ketones
O
Zn / HCl
85
NH2
H
110
O
O
O
O
protect alcohols
OH
+
O
O
H
109
1. NaBD4
2. workup
or
1. LiAlD4
2. workup
O
OH
O
D D
N 1. LiAlD4
C
2. workup
D
107
O
105
OH
1. NaBD4
2. workup
or
1. LiAlD4
2. workup
OH
Using NaBD4 or LiAlD4 will
show where the reaction occurs.
Also, LiBH4 and NaAlH4 are
available, all at greater expense.
OH
only
O
OH
1. LiAlH4
2. workup
102
104
OH
only
R
1. LiAlH4
2. workup
1. NaBH4
2. workup
or
1. LiAlH4
2. workup
O
O
OH
H
SH SH
BF3
(-H2O)
S
S
H
thioacetal
S
S
H
thioacetal
Raney Ni
(loaded with H2)
H3C
CH3
9 3C starting compound = CH3CH2CH3
Br
1
2
3
Br
E2 at 1o, 2o, 3o
free radical substitution
4
5
Br
Br
1. 3 eqs.
NaNR2
2. workup
Br
Br
double E2
Br
Br
HO
8
10
HBr
ROOR
h
Br
11
O
Br
O
O
OH
E2 > SN2 at 2o RX
OH
12
NaOH
SN2 at Me, 1o
E2 > SN2 at 2o
Br
SH
NaSH
O
Br
SN2 at Me, 1 , 2
o
SN2 at Me, 1 , 2
19
20
1. NaN3
2. LiAlH4
Br 3. workup
Br
NH2
SN2 at Me, 1o, 2o
22
1. NaOH
2. Br
O
N
R
R
SN2 at Me, 1o, 2o
25
26
C
O
S
1. n-BuLi
2. Br
E2 at 1o, 2o, 3o
27
1. NaNR2
2.
Br
C
S
N
rxn 2 = SN2 at Me, 1o
30
S
1. n-BuLi
2. Br
S
E2 > SN2 at 2
o
S SN2 at Me, 1o, 2o
Br
R
E2 at 1o, 2o, 3o
1. n-BuLi
2.
Br
1. NaOH
2.
3. NaOH
N
R
SN2 at Me, 1o, 2o
29
o
SN2 at Me, 1o, 2o
H
NaCN
SN2 at Me, 1o, 2o
1. NaNR2
2. Br
O
NH
Br
N
28
21
NH2
1. n-BuLi
2.
Br
H
3. NaOH
Br NaCN
SN2 at Me, 1 , 2
24
23
NH2
S
o
SN2 at Me, 1o, 2o
NH
O
SH
o
1. NaN3
2. LiAlH4
3. workup
SH
1. NaOH
2. Br
S
o
NaSH
SN2 at Me, 1o, 2o
O
18
SH
o
15
1. NaOH
2.
Br
17
Br
NaOH
OH
SN2 at Me, 1o, 2o
16
1. NaH
2. Br
9
1. NaOH
2. Br
O
OH
C=O addition
Br
OH
SN2 at Me, 1o, 2o
1. 3 eqs.
NaNR2
2. O
H
3. workup
Br
14
1. NaOH
2.
Br
zipper reaction
anti-Markovnikov
13
6
1. 3 eqs.
NaNR2
2.
Br
1. excess
NaNR2
2. workup
3. workup rxn 2 = SN2 at less
hindered C
Br
free radical substitution
rxn 2 = SN2 at Me, 1o
1. 3 eqs.
NaNR2
2. O
7
Br
2 eqs.
Br2
h
O
K
Br2
h
S
S
S S 2 at Me, 1o, 2o
N
NH2
10 31
32
1. n-BuLi
2. Br
S
S
dithiane = SN2 at Me, 1o, 2o
dithiane = SN2 at Me, 1 , 2
S
H
aldehydes
S
O
O
HgX2/H2O
H
S
S
36
HgX2/H2O
O
HgX2/H2O
o
35
O
S
S
o
S
33
S
S
S
34
S
1. n-BuLi
2.
Br
S
HgX2/H2O
S
S
aldehydes
37
38
1. LDA,-78oC
2.
Br
O
O
RO
Br Ph
S
Ph
SN2 at Me, 1o, 2o
Ph
O
1. n-BuLi
2. H2C=O
S
49
47
Ph
S
Ph
Ph
Ph
Br
Ph
51
Br
Ph
Ph
Ph
Ph
Ph
Br
Ph
Ph
P
Ph
SN2 at Me, 1o, 2o
Ph
Br
Ph
Ph
Z alkenes
Ph
P
Ph
Br
H
Ph
P
Ph
Br
Ph
Br
Ph
H
Ph
Z alkenes
N2
O
MeO
E alkenes
1. n-BuLi
2. CH3CH=O
Ph
Z alkenes
P
OMe O
1. n-BuLi
2. CH3CH=O
3. n-BuLi
4. workup
P
59
H
3. n-BuLi
4. workup
Br
Br
1. n-BuLi
2. O
Z alkenes
1. n-BuLi
2.
O
58
Ph
57
Ph
1. n-BuLi
2. O
P
Ph
P
1. n-BuLi
2. CH3CH=O
56
Ph
1. n-BuLi
2. H2C=O
P
54
Ph
Br
55
Br
Ph
P
1. n-BuLi
2. H2C=O
P
O
S
53
Ph
52
1. n-BuLi
2.
O
O
P
SN2 at Me, 1o, 2o
O
Br
Ph
Br
48
Ph
Br
Ph
P
Br
P
1. n-BuLi
2. H2C=O
S
1. n-BuLi
2.
O
50
Ph
Ph
Ph
SN2 at Me, 1o, 2o
Ph
Ph
Ph
Ph
enolate rxn 2 = SN2 at Me, 1o, 2o
S
S
Ph
Br
Ph
C
H3C
o
Ph
Br
Br
N
C
45
S
46
Ph
enolate rxn 2 = SN2 at Me, 1 , 2
Ph
Ph
1. LDA,-78oC
N 2. Br
N
C
H3C
44
Ph
RO
42
o
O
enolate rxn 2 = SN2 at Me, 1o, 2o
1. LDA,-78oC
N 2.
Br
C
43
1. LDA,-78oC
2.
Br
O
RO
O
RO
enolate rxn 2 = SN2 at Me, 1o, 2o
O
enolate rxn 2 = SN2 at Me, 1o, 2o
41
1. LDA,-78oC
2. Br
O
39
1. LDA,-78oC
2. Br
O
enolate rxn 2 = SN2 at Me, 1o, 2o
40
ketones
ketones
60
1. RO
2.
O
H
Ph
Br
E alkenes
11 61
62
O
OH
OH
O
CrO3
py.
1o alcohol
aldehydes
64
OH
Jones
1o alcohol
Jones
69
68
O
1. NaOH
2.
Br
O
O
OH
OH
Cl
72
O
O
NH2
O
O
O
Cl
75
O
76
O
O
O
77
OH
O
SH
O
O
O
H
O
77
1. TsOH (-H2O)
H
N
O
1. NaH3BCN HN
2. workup
H
o
2. NaH3BCN
3. workup
2 amines
N
3 amides
75
N
N
1. NaH3BCN
2. workup
HN
2o amines
78
Br
OH
1. TsOH (-H2O)
H
N
2. NaH3BCN
3. workup
3o amines
N
3o amines
81
83
82
O
N
80
79
Br
2o amines
O
o
make imines
76
1. Mg or Li
2. H2C=O
3. workup
HN
H
make imines
N
O
O
TsOH
(-H2O)
NH2
O
N
H
O
S
74
TsOH
(-H2O)
NH2
NH2
N
H
SH
O
O
O
S
O
O
73
N
O
Cl
O
O
O
78
O
H
N
Cl
74
73
Cu
Li
O
OH
N
H
O
Cl
O
Fischer ester syn.
71
OH
ketones
TsOH
(-H2O)
O
O
SOCl2
O
Cl
PCC
2o alcohol
66
O
OH
rxn 2 = SN2 at Me, 1o, 2o
70
OH
carboxylic acids
ketones
67
O
CrO3
py.
65
O
CrO3
H2O
2o alcohol
O
OH
CrO3
H2O
H
PCC
63
1. Mg or Li
2. H2C=O
3. workup
1. Mg or Li
2. O
84
OH
Br
H
3. workup
OH
12 85
1. Mg or Li
2. O
1. Mg or Li
2. O
86
OH
Br
89
OH
Br
93
1. Mg or Li
Br 2. O=C=O
3. workup
95
OH
Br
Br
99
OH
Br
OH
102
104
Br
105
1. Mg or Li
O
2.
O
OH
3. workup
108
110
112
O
1. Li
Br 2. CuBr
OH
3. workup
113
1. Li
2. CuBr
111
1. only Li
2.
O
Br
O
1.
Cu
cuprates
O
114
1.
O
Cu
O
Li
cuprates
Cu
Li
cuprates
Cu
Li
OH
Br
107
1. only Li
2.
O
O
3. workup
1. Mg or Li
O
2.
Br
3. workup
106
Br
1. Mg or Li
2.
N
C
OH
3. workup
3. workup
OH
3. workup
OH
Br
3. workup
1. Mg or Li
2.
O
101
OH
3. workup
1. Mg or Li
2. O
Br 3. workup
1. Mg or Li
2.
N
C
Br
1. Mg or Li
2. O
Br
OH
3. workup
109
O
OH
OH
1. Mg or Li
2. O
98
1. Mg or Li
2.
O
103
Br
96
1. Mg or Li
2. O
3. workup
Br
1. Mg or Li
2. O=C=O
3. workup
3. workup
1. Mg or Li
2. O
100
O
O
3. workup
OH
Br 3. workup
Br
OH
Br
92
OH
1. Mg or Li
2. O
97
1. Mg or Li
2. O
Br
O
3. workup
94
90
OH
H
O
3. workup
1. Mg or Li
2. O
OH
Br
3. workup
1. Mg or Li
2. O
H
O
3. workup
91
1. Mg or Li
2. O
3. workup
1. Mg or Li
2. O
Br
OH
Br
H
3. workup
88
87
2. workup
Li
cuprates
O
2. workup
13 1.
115
1.
116
Cu
Br
Cu
Li
cuprates
117
Br
Li
2. workup
Cu
2. workup
1.
119
1.
Li
cuprates
121
Li
cuprates
2. workup
1. Mg or Li
2.
Br
122
O
OH
Li
cuprates
2. workup
123
O
OH
SN1 at 2o, 3o
OH
PBr3
129
Br
OH
SOBr2
Br
OH
SOBr2
SN2 at Me, 1o
1. TsCl, py.
2. NaBr
Br
prevents rearrangement at 2o ROH
SN1 at 2o, 3o
131
Br
Br
SN1 at 2o, 3o
128
OH
Br
PBr3
Br
SN2 at Me, 1o
127
OH
HBr
OH
126
125
Br
OH
130
2. workup
SN2 at Me, 1o
124
HBr
O
Cl
Cl
3. workup
Cl
3. workup
OH
O
Cu
1. Mg or Li
2.
Br
1.
Cl
Cu
Br
2. workup
120
O
O
Cu
Br
Li
cuprates
cuprates
118
1.
132
1. TsCl, py.
2. NaBr
prevents rearrangement at 2o ROH
133
O
H
134
1. NaBH4
2. workup
or
1. LiAlH4
2. workup
O
OH
135
1. NaBH4
2. workup
or
1. LiAlH4
2. workup
O
only
OH
C
R 1. LiAlH4
2. workup
O
N
138
1. LiAlH4
2. workup
C
OH
1. LiAlH4
2. workup
OH
137
136
only
O
OH
N
1. LiAlH4
2. workup
NH2
140
139
Using NaBD4 or LiAlD4 will
show where the reaction occurs.
Also, LiBH4 and NaAlH4 are
available, all at greater expense.
O
142
143
O
H
TsOH (-H2O)
HO
OH
O
protect aldehydes and ketones
O
H
O
NH2
141
1. NaBD4
2. workup
or
1. LiAlD4
2. workup
OH
O
D
OH
only
O
R 1. LiAlD4
2. workup
D
D
144
TsOH (-H2O)
HO
OH
O
protect aldehydes and ketones
O
OH
O
TsOH
O
O
protect alcohols
14 145
146
OH
O
O
O
TsOH
O
O
H3O+
H2O
147
O
deprotect aldehydes and ketones
H3O+
H2O
OH
H3O+
H2O
O
Zn / HCl
H
Clemmenson's reduction
O
O
deprotect alcohols
deprotect alcohols
151
152
153
O
O
Zn / HCl
O
H2NNH2
RO / 
H2NNH2
RO / 
H
Clemmenson's reduction
Miscellaneous other reactions not required for our course. You can add others, if needed.
1
3
2
O
SH SH
BF3
(-H2O)
S
H
H
S
Raney Ni
S
(loaded with H2)
S
S
H
H
thioacetal
4
S
O
Raney Ni
(loaded with H2)
H
H
thioacetal
H
H2
C
7
OH
CH3
H
O
8
Pr4N
Tetrapropylammonium perruthenate
Ley oxid. (no H2O = alds, with H2O = acids)
10
11
CrO3, py.
CH2Cl2
O
OH
S
S
S
H
thioacetal
S
Raney Ni
(loaded with H2)
H
H
thioacetal
O
periodinane
O
O
I OAc
AcO OAc
R
OH
DMSO
N C N
R
R
R
R
Oppenauer oxidation
OH
O
Swern oxid.
15
Moffatt oxid
Swern oxid
Periodinane oxid
Collins oxid
17
CO2
Et3N
Cl
O
oxalyl chloride
+ urea
Moffatt oxid.
14
R
DMSO
O
Cl
12
DCC
R
Meerwein–Ponndorf–Verley reduction
Dess-Martin oxid.
16
S
more environmentally friendly (alds,kets)
more environmentally friendly (alds,kets)
9
(possible side reactions)
(possible side reactions)
OH
O
OH
O
OH
O
O
OH
Al(Oi-Pr)3)
Al(Oi-Pr) )
Collins oxid. makes aldehydes
and ketones
13
S
3
R
OH
SH SH
BF3
(-H2O)
thioacetal
RuO4
SH SH
BF3
(-H2O)
6
O
H3C
H
H
5
H
thioacetal
150
OH
O
O
O
deprotect aldehydes and ketones
149
148
H3O+
H2 O
H
H
protect alcohols
O
O
18
O
CO
15 Each of the following proposed synthetic approaches is built on the earlier preparations. Specific reactions are given for the 1C,
2C and 3C compounds. Those are used to make 4C compounds, which are then used to make 5C compounds, which are then
used to make 6C compounds. Many example sequences are not efficient or practical, but given to show how reactions can be
used. All of the C-C bond forming reactions involve nucleophile/electrophile strategies. Reagents are only shown for the C1,
C2 and C3 compounds. It is assumed that you can supply the necessary reagents for C4 and higher compounds (they are repeats
of the 1C, 2C and 3C examples), though brief hints may be given under the reaction arrows. The target molecules are mainly
alcohols aldehydes, ketones or acids. 4C targets (alcohols, aldehydes, ketones and carboxylic acids)
1. butan-1-ol, butanal, butanoic acid
OH
(Mg or Li)
4C
OH
Br
O
Br
O
CH2
1C
(Mg or Li)
4C
3C
O
Br
O
OH
O
2C
2C
OH
4C
O
(Mg)
3C
1C
(LiAlH4)
4C
OH
O
Br
OR
4C
O
Br
(enolate
LDA,-78oC)
C
2C
2C
OR
CH3
(Ph)3P
(BH3)
4C
(P ylid)
4C
3C
O
H
1C
H
4C
(R2BH)
(NaNR2
SN2)
4C
H
2C
2C
O
4C
(nBuLi
SN2)
S
O
Br
4C
4C
OH
N
NaCN
C
(SN2)
3C
C
H
1C
4C
(DIBAH)
(Pd,H2)
4C
(NaNR2)
CH2
1C
4C
OH
O
O
OH
OH
4C
3C
1C
N
OH (acid or
base)
Br
S
O
Br
3C
4C
(Pd,H2)
4C
(NaNR2)
2C
2C
16 2. butan-2-ol, butan-2-one
O
OH
O
OH
Br
(Mg or Li)
4C
2C
2C
3C
OH
Br
O
(Mg or Li)
4C
CH3
1C
3C
O
4C
(P ylid)
O
O
H
Br
H
3C
(Li)
O
(cuprate)
4C
(n-BuLi)
4C
Br
CH3
1C
Cl
3C
(Li)
4C
Br
N
(Mg or Li)
Br
OH
2C
CH3
1C
(Mg or Li) H3C
2C
(H3O+)
2C
Cl
3C
4C
4C
2C
OH
4C
2C
2C
O
Br
(NaNR2)
Br
N
4C
Br
O
(H3O+)
2C
O
(cuprate)
4C
CH3
1C
2C
C
3C
O
O
S
2 eqs.
1C
4C
1C
O
O
C
CH3
1C
OH
3C
O
1C
CH3
2 eqs.
4C
Br
CH3
(Ph)2S
3C
O
Br
2C
Br
S
(Ph)3P
(H3O+)
4C
Br
(S ylid)
4C
4C
OH
O
O
(LiAlH4)
H
2C
4C
4C
O
OH
O
(NaNR2)
(Pd,H2)
CH3
1C
H
H
4C
OH
OH
Br
(Mg or Li)
2C
4C
(Pd,H2
quinoline)
4C (Z )
(H3O+)
Br
H3C 1C
(NaNR2)
4C
4C
(Na, NH3)
4C (E )
3. 2-methylpropan-1-ol, 2-methylpropanal, 2-methylpropanoic acid
OH
Br
(Mg or Li)
4C
OH
O
O
CH3
(Ph)3P
CH2
1C
3C
Br
O
3C
(BH3)
4C
1C
(P ylid)
4C
OH
Br
O
O
C
OH
(Mg)
4C
(H2SO4)

O
3C
O
1C
(acid or
base)
4C
H
1C
(SN2)
4C
3C
O
O
OR
(LiAlH4)
C
NaCN
4C
OH
4C
N
Br
OH
4C
3C
O
N
C
(DIBAH)
O
OR
(enolate
LDA,-78oC)
CH3
1C
(Mg or Li)
4C
Br
4C
S
Br
H
(n-BuLi)
4C
4C
S
3C
1C
4. 2-methylpropan-2-ol
OH
Br
CH3
(Mg or Li) 1C
4C
O
OH
3C
(Mg or Li)
4C
2C
OR
(H3O+)
Br
CH3
1C
(P ylid) 4C
(LiAlH4)
4C
4C
(S ylid)
3C
Br
1C
4C
(SN1)
4C
4C
(cuprate)
3C
1C
1C
Br
Br2
h
CH3
(Ph)2S
CH3
(Ph)3P
4C
Br
O
OH
O
O
OH
Br
2 eqs.
OH
4C
O
Br
CH3
1C
17 5C targets (alcohols, aldehydes and carboxylic acids)
1. pentan-1-ol, pentanal, pentanoic acid
OH
Br
O
OH
Br
O
CH2
(Mg or Li) 1C
5C
4C
(Mg or Li)
5C
O
Br
O
2C
3C
OH
O
O
Br
C
OH
5C
(Mg)
O
1C
(LiAlH4)
5C
4C
OH
O
OR
5C
Br
(enolate
LDA,-78oC)
3C
OR
2C
CH3
(Ph)3P
(BH3)
5C
(P ylid)
5C
H
4C
O
1C
O
Br
H
5C
(R2BH)
H
(NaNR2
SN2)
5C
3C
2C
O
Br
S
S
1C
(n-BuLi)
5C
4C
O
Br
N
N
NaCN
C
OH (acid or
base)
5C
(SN2)
5C
OH
C
1C
4C
(Pd,H2)
5C
5C
OH
O
(Pd,H2)
CH2
5C
(DIBAH)
OH
O
OH
H
5C
(NaNR2) 1C
4C
5C
5C
(NaNR2) 2C
3C
2. pentan-2-ol, pentan-2-one
O
OH
(Mg or Li)
5C
4C
H
Br
OH
CH3
1C
5C
Br
Br
(LiAlH4)
5C
C
4C
(Mg or Li)
5C
O
(P ylid)
N
(Mg or Li)
H
O
(cuprate)
O
Cl
CH3
1C
O
5C
1C
(Li)
4C
OH
(SOCl2)
5C
Br
O
CH3
1C
5C
5C
(NaNR2)
2 eqs.
3C
CH3
1C
3C
O
(Li)
3C
3C
5C
Cl
O
Br
HO
2C
Br
O
2C
1C
Br
5C
Br
(H3O+)
S
(cuprate)
OH
4C
O
(n-BuLi)
O
2 eqs.
5C
Br
S
Br
O
4C
CH3
CH3
Br
5C
C
2C
3C
O
Br
4C
2C
Br
(Ph)3P
5C
H
3C
5C
CH3
1C
O
(HgX2
H2O)
O
(NaNR2)
(Pd,H2)
5C
1C
O
OH
OH
CH3
Br
N
3C
2C
(Mg or Li)
(Ph)2S
H
4C
(S ylid)
O
5C
5C
O
OH
O
5C
2C
Br
O
OH
5C
H
3C
(Mg or Li)
OH
O
(enolate
LDA,-78oC)
2C
O
3C
2C
18 3. pentan-3-ol, pentan-3-one
O
OH
H
3C
(Mg or Li)
5C
Br
2C
O
O
OH
2 eqs.
5C
H
2C
(Mg or Li)
O
Br
N
Br
OH
OR
1C
Br
5C
CH3
1C
(Mg or Li)
O
Br
O
O
4C
O
(Li)
Br
2 eqs.
C
(Mg or Li)
5C
3C
(cuprate)
5C
2C
OH
OH
Cl
3C
O
2C
5C
OH
3C
S
O
2C
Br
2 eqs.
(Pd,H2)
5C
(NaNR2)
5C
H
2C
(n-BuLi)
5C
3C
2C
S
4. 2-methylbutan-1-ol, 2-methylbutanal, 2-methylbutanoic acid
OH
O
O
Br
(Mg or Li)
5C
Br
CH2
1C
4C
(Mg)
5C
O
4C
1C
O
O
N
NaCN
OH
(acid or
base)
5C
5C
O
OH
(LiAlH4)
(enolate
LDA,-78oC)
5C
O
2 eqs.
5C
(Li)
S
Br
H
OR
(n-BuLi)
5C
4C
S
OH
O
Br
H
O
3C
2C
5C
(DIBAH)
5C
O
Br
OR
H
1C
4C
(SN2)
N
C
Br
C
5C
O
C
OH
Br
O
OH
H
4C
(BH3)
5C
1C
CH3
(Ph)3P
4C
(P ylid)
5C
1C
5. 2-methylbutan-2-ol
OH
Br
5C
3C
2C
O
(Mg or Li)
5C
(Mg or Li)
5C
Br
O
5C
4C
(LiAlH4)
O
4C
(S ylid)
(LiAlH4)
O
5C
(mCPBA)
(P ylid)
5C
Br
(Ph)3P
4C
OH
O
+
(H3O )
(P ylid)
5C
OH
5C
CH3
1C
4C
OH
O
5C
Br
(Ph)2S
OH
5C
CH3
1C
3C
O
CH3
(Mg or Li) 1C
Br
2 eqs.
OR
CH3
1C
4C
O
OH
Br
OH
OH
5C
OH
O
(Mg or Li)
5C
O
(Pd,H2)
5C
2C
5C
(cuprate)
2C
5C
Br
Br
Br2
h
5C
OH
OH
Br
(SN1)
(H3O+)
5C
Br
(Ph)3P
3C
CH3
1C
3C
(NaNR2)
3C
2C
19 6. 2-methylbutan-3-ol, 2-methylbutan-3-one
OH
OH
CH3
(Mg or Li)
5C
3C
(LiAlH4)
(S ylid)
5C
(Mg or Li)
4C
4C
(Mg or Li)
5C
(S ylid)
1C
2C
O
O
5C
2C
HO
4C
O
P OMe
1C N OMe
2
H
RO
CH3
1C
O
3C
(P ylid)
5C
O
Br
(Li)
Br
(Ph)3P
(BH3)
5C
2C
5C
2C
3C
2C
O
O
OH
3C
(H3O+)
H3C
4C
(Ph)2S
H
O
Br
C
OR
1C
3C
OH
2 eqs.
5C
N
C
Br
(Li)
N
Br
CH3
1C
Br
S 1C 1C
Br
2 eqs.
5C
(n-BuLi)
5C
CH3
4C
Br
CH3
1C
O
CH3
O
H
S
H
(Ph)2S
Br
O
O
O
Br
OH
5C
(Mg or Li)
O
O
5C
5C
H
2C
OH
O
Br
O
Br
4C
7. 3-methylbutan-1-ol, 3-methylbutanal, 3-methylbutanoic acid
OH
Br
O
(Mg or Li)
5C
2C
O
O
C
3C
Br
S
Br
O
CH2
(Mg or Li)
5C
Br
OH
O
HO
4C
1C
(Mg or Li)
5C
(n-BuLi)
5C
HO
4C
1C
O
OH
OH
(LiAlH4)
5C
Br
(enolate
LDA,-78oC)
RO
5C
3C
(R2BH)
5C
O
2C
OH
H
(Li)
5C
H
5C
O
2 eqs.
OH
1C
Br
CH2
4C
O
C
HO
(Mg or Li)
5C
1C
O
4C
1C
O
Br
1. O3, -78oC
2.
H
5C
6C
t-butoxide
Br
PBr3
6C
(Mg or Li)
OH
6C
OH
O
1. O3, -78oC
2.
1. O3, -78oC
2.
HO
5C
6C
5C
6C
4C
1C
Br
O
O
OR
4C
O
(Mg or Li)
O
H
RO
5C
8. 2,2-dimethylpropan-1-ol, 2,2-dimethylpropanal, 2,2-dimethylpropanoic acid
Br
5C
O
H
1C
O
(DIBAH)
5C
O
4C
5C
5C
CH3
(Ph)3P
H
(BH3)
5C
C
H
(acid or
base)
5C
Br
(P ylid)
4C
N
C
S
1C
O
O
N
H
O
O
2C
4C
O
P OMe
N2 OMe
20 6C targets (alcohols, aldehydes, ketones and carboxylic acids)
1. hexan-1-ol, hexanal, hexanoic acid
Br
Br
OH
OH
OH
O
(Mg or Li)
6C
(Mg or Li)
5C
5C
1C
O
(R2BH)
Br
OH
HBr
6C
6C
2C
6C
(NaNR2
SN2)
H
O
4C
PBr3
CH2
2C
excess
(NaNR2)
4C
4C
Br
(NaNR2)
6C
3C
3C
OH
OH
O
Br
PPh3
(BH3)
(P ylid)
6C
H3C
H
5C
CrO3
py.
1C
6C
5C
(R2BH)
O
Hg+2
H2 O
H
S
S
n-BuLi
S
S
6C
5C
OH
Br
1C
O
5C (made above)
O
Br
(enolate
LDA,-78oC)
O
R
R
O
O
(LiAlH4)
6C
4C (made above)
6C
O
O
(Mg or Li)
(acid or
base)
O
C
OH
N
C
O
5C (made above)
H
6C
2C
(DIBAH)
Br
6C
5C (made above)
OH
1C
6C
6C
(SN2)
OH
O
Br
NaCN
OH
(Pd,H2)
6C
6C
CH2
(NaNR2)
5C (made above)
1C
5C (made above)
OH
O
(Pd,H2)
6C
6C
OH (NaNR2)
4C
2C (made above)
21 2. Other 6C target molecules
O
O
OH
H
6C
6C
OH
O
6C
6C
OH
6C
O
OH
6C
6C
O
OH
O
H
OH
6C
O
6C
6C
6C
6C
OH
O
O
HO
6C
6C
OH
H
6C
O
6C
6C
OH
OH
O
6C
H
6C
6C
O
HO
O
6C
6C
O
OH
6C
O
O
O
H
6C
O
6C
6C
6C
6C
HO
H
OH
HO
6C
6C
O
OH
6C
6C
OH
O
OH
H
OH
OH
6C
6C
H
6C
OH
HO
6C
OH
6C
6C
O
O
OH
6C
22 Alkene reactions
Ethene –does not show regioselectivity or stereoselectivity
1
2
Br
3
H2SO4
H2 O
HBr
4
CH3
1. HgX2 / CH3OH
2. NaBH4
5
Br
O
1. BH3
2. Br2, CH3O
8
Br
Br
Cl
mCPBA
O
14
1. mCPBA
2. HO / H2O
OH
anti addition, SN1-like
15
H3CO
anti addition, SN2-like
anti addition, SN1-like
17
2
18
1. O3, -78oC
2. NaBH4
O
CH2
cuts C=C, makes aldehydes and ketones
1. O3, -78oC
2. H2O2 / HO
OH
2
cuts C=C, makes acids and ketones
OH
HO
21
H2 / Pd
or
D2 / Pd
CH3
H3C
syn addition
O
2
H
CH3
cuts C=C, makes two alcohols
20
1. mCPBA
2. CH3O / CH3OH
OH
OH
H3CO
anti addition, SN2-like
OH
HO
1. mCPBA
2. CH3OH+ / CH3OH
HO
1. O3, -78oC
2. CH3SCH3
1. mCPBA
2. H3O+ / H2O
O
syn addition
13
Br
12
H
O O
anti + backside = syn
Br2
H2O
HO
can make
epoxides
anti addition
anti addition
11
OsO4
or
KMnO4
9
Br2
can make
alkynes
O
1. Br2 / H2O
2. NaOH
19
anti-Markovnikov addition
syn addition
Br
10
OH
1. BH3
2. H2O2, HO
anti-Markovnikov addition
anti-Markovnikov addition
syn addition
16
6
HBr
ROOR
h
no rearrangement
OH
same as 1, but no rearrangement
rearrangement possible
rearrangement possible
7
1. HgX2 / H2O
2. NaBH4
OH
syn addition
22
23
24
25
26
27
OH
23 Alkene reactions
Propene –shows regioselectivity but not stereoselectivity
1
2
Br
3
HBr
rearrangement possible
rearrangement possible
4
CH3
1. HgX2 / CH3OH
2. NaBH4
Br
6
HBr
ROOR
h
Br
8
9
Br2
Br2
H2 O
Br
Br
anti-Markovnikov addition
syn addition
O
14
1. mCPBA
2. HO / H2O
OH
15
1. mCPBA
2. CH3OH+ / CH3OH
1. mCPBA
2. CH3O / CH3OH
OH
OH
HO
H3CO
H3CO
anti addition, SN2-like
anti addition, SN1-like
anti addition, SN2-like
16
1. O3, -78oC
2. CH3SCH3
O
CH2
17
1. O3, -78oC
2. NaBH4
O
H
cuts C=C, makes aldehydes and ketones
OsO4
or
KMnO4 HO
OH
CH3
18
OH
syn addition
H2 / Pd
or
D2 / Pd
1. O3, -78oC
2. H2O2 / HO
OH
H
O
O
OH
OH
cuts C=C, makes acids and ketones
cuts C=C, makes two alcohols
20
OH
HO
anti addition, SN1-like
syn addition
13
19
1. mCPBA
2. H3O+ / H2O
O
H
O O
anti + backside = syn
can make
epoxides
12
Cl
O
Br
HO
anti addition
mCPBA
11
1. Br2 / H2O
2. NaOH
can make
alkynes
anti addition
10
OH
1. BH3
2. H2O2, HO
anti-Markovnikov addition
syn addition
anti-Markovnikov addition
1. BH3
2. Br2, CH3O
OH
same as 1, but no rearrangement
5
O
no rearrangement
7
1. HgX2 / H2O
2. NaBH4
OH
H2SO4
H2O
21
D
D
syn addition
22
23
24
25
26
27
24 Alkene reactions
Cyclohexene – shows stereoselectivity but not regioselectivity
1
Br
2
HBr
4
O
Br
1. BH3
2. H2O2, HO
anti-Markovnikov addition
syn addition
anti-Markovnikov addition
no rearrangement
1. BH3
2. Br2, CH3O
Br
8
9
Br
Br2
anti-Markovnikov addition
syn addition
10
anti addition
mCPBA
H
O O
anti + backside = syn
13
OH
1. mCPBA
2. HO / H2O
14
syn addition
1. mCPBA
2. CH3OH+ / CH3OH
OH
anti addition, SN2-like
anti addition, SN1-like
H
16
1. O3, -78oC
2. CH3SCH3
H
cuts C=C, makes aldehydes and ketones
19
OsO4
or
KMnO4
syn addition
O
O
O
OH
anti addition, SN2-like
18
O
OH
OH
21
H2 / Pd
or
D2 / Pd
D
syn addition
D
CH3
OH
OH
cuts C=C, makes acids and ketones
cuts C=C, makes two alcohols
OH
1. O3, -78oC
2. H2O2 / HO
O
O
O
OH
OH
20
1. mCPBA
2. CH3O / CH3OH
CH3
17
1. O3, -78oC
2. NaBH4
OH
anti addition, SN1-like
15
OH
OH
1. mCPBA
2. H3O+ / H2O
O
O
can make
epoxides
12
Cl
1. Br2 / H2O
2. NaOH
Br
Br2
H2O
Br
anti addition
11
OH
6
HBr
ROOR
h
CH3
OH
1. HgX2 / H2O
2. NaBH4
same as 1, but no rearrangement
5
1. HgX2 / CH3OH
2. NaBH4
3
rearrangement possible
rearrangement possible
7
OH
H2SO4
H2O
22
23
24
25
26
27
25 Alkene reactions
1-methylcyclohexene – shows stereoselectivity and regioselectivity
2
1
HBr
CH3
Br
rearrangement possible
H2SO4
H2O
achiral
CH3
OH
rearrangement possible
3
achiral
4
1. HgX2 / H2O
2. NaBH4
CH3
OH
same as 2, but no rearrangement
5
HBr
ROOR
h
enantiomers
Br
H
H
H
CH3
H
Br
H
H
9
enantiomers
CH3
OH
can make epoxides
anti addition
mCPBA
anti addition
15
1. mCPBA
2. CH3O / CH3OH
H
17
OH
CH3
OH
CH3
H
OH
O
1. O3, -78oC
2. CH3SCH3
syn addition
O CH
3
CH3
CH3
H
OH
H
O
ketone-aldehyde
O
cuts C=C, makes aldehydes and ketones
18
1o alcohol
2o alcohol
1. O3, -78oC
2. H2O2 / HO
OH
O
ketone-acid
O
cuts C=C, makes two alcohols
OsO4
or
KMnO4
OH
CH3
enantiomers
H
OH
19
OH
H
OH
CH3
CH3
OH
OH
CH3
enantiomers
1. O3, -78oC
2. NaBH4
1. mCPBA
2. CH3OH2+ / CH3OH
enantiomers
H
anti addition, SN1-like
16
O
O
anti addition, SN2-like
14
OH
CH3
CH3
O
O
anti + backside = syn
OH
H
CH3
OH
anti addition, SN2-like
Br
CH3
1. Br2 / H2O
2. NaOH
O
OH
CH3
Br
enantiomers
1. mCPBA
2. H3O+ / H2O
enantiomers
H
Br
H
10
anti addition, SN1-like
1. mCPBA
2. HO / H2O
Br
Br2
syn addition
13
enantiomers
H
12
O
H
CH3
H
anti-Markovnikov addition (syn)
O
H
O O
CH3
CH3
OH
CH3
enantiomers
Cl
achiral
enantiomers
OH
H
H
OH
1. BH3
2. H2O2, HO
8
Br
H
Br
Br2
H2O
O
6
H
CH3
CH3
anti-Markovnikov addition
syn addition
11
enantiomers
Br
H
diastereomers
enantiomers
H
Br
1. BH3
2. Br2, CH3O
CH3
no rearrangement
CH3
anti-Markovnikov addition
7
1. HgX2 / CH3OH
2. NaBH4
achiral
cuts C=C, makes acids and ketones
H
OH
OH
CH3 enantiomers
OH
H
CH3
OH
20
H2 / Pd
or
D2 / Pd
syn addition
H
D
D
D
CH3 enantiomers
H
CH3
D
26 Alkene Reactions
27 28 29 O
O
H
O
H
O
H
H
H
H
H
H
H
O
O
H
O
O
-78oC
1. O3 /
2. CH3SCH3
f orms ozonides and is
reduced to aldehydes
and ketones depending
on the substitution of
the alkene carbons
O
CH3
CH3
O
H
O
H
H
H
O
O
O
H
O
H
O
H
H
O
O
30 Random course reactions, focusing more on alkene and alkyne reactions. A few other reactions are mixed in. The
only point of synthetic sequences is to show reactions. The sequences are not always logical from a synthetic point of
view (sometimes the same compound is made more than once in a sequence to show variety).
Br
Br
Br2
h
O
K
H2SO4

NaOH
Br
Br2
h
OH
HBr
ROOR
h
O
K
Br
O
K
Br
Br2
h
OH
H2SO4
H2O
O
K
H2SO4

OH
Br
1. Mg
2. O
H2SO4

H
3. workup
1. BH3
2. H2O2, HO
OH
OH
Br
1. Mg
2. O
3. workup
Br
1. Mg
2. O
H H
3. workup
H2SO4
H2O
H2SO4

OH
OH
Br
H2SO4

HBr
ROOR
h
O
K
31 HO
CH3 1. n-BuLi
Ph
2.
Ph P CH2
O
Ph Br
Br2
H2O
Z alkene
mixture
NaOH
Br (buffer)
O
H3 O +
H2O
HO
OH
32 CH3
O
Ph
Ph P CH2
Ph Cl
O
1. n-BuLi
2. O
Br
OH
1. BH3
2. H2O2, HO
Br
1. TsCl, py
2. NaBr
1. Mg
2. CO2
3. workup
Br
Br
Br
H2SO4
H2O
O
H
2 eqs.
Br2
h
Br 1. excess
NaNR2
2.
Br
2 eqs.
Br2
h
Br
Br
Br
Br
Br
Br
H
2 eqs.
Br2
h
2 eqs.
Br2
h
Br
Br
H
3. workup
Br
Br
OH
1. excess
NaNR2
2. O
2 eqs.
Br2
h
H
1. excess
NaNR2
2. O
H
3. workup
OH
2 eqs.
Br2
h
OH
O
O
1. excess
NaNR2
2. workup
CO2H
CrO3
H2O
OH
H
2 eqs.
Br2
h
OH
1. Mg
2. O
TsOH (-H2O)
OH
OH
1. NaBH4
2. workkup
3. workup
O
2 eqs.
Br2
h
O
H
H2SO4
H2O
1. excess
NaNR2
2. workup
H
1. excess
NaNR2
2.
Br
1. excess
NaNR2
2. O
OH
H
3. workup
Br
Br
1. excess
NaNR2
2. O
3. workup
OH
33 C1
C6 target molecules with "X" functionality at unique positional and skeletal positions. (X = Br, OH are particularly versital groups).
Starting sources of carbon.
CH4
CO2
Br 1C
4C
3C
2C
X
X
X
X
X
X
X
X
CH3
NaCN
5C
X
X
X
X
X
X
X
X
6C
X
6C
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
39 additional C7H15X
Examples of carbon and hydride nucleophiles in our course.
R
+
R (MgBr )
Grignard
reagents
R
Ph
H
CH2
H
Ph
Al
Ph
"P" ylids
Ph
"S" ylids
H
H
H
LAH
CH2
B
H
N
H
DIBAH
diisobutyl
aluminum ydride
H
borohydride
CH2
H2C
N
C
Li
S
nitrile
enolates
ester
enolates
Al
H
Li
C
O
ketone
enolates
Na
S
Li
C
R
H3C
terminal
acetylides
H
Li
C
Na
R
O
Li
C
Na
cyanide
cuprate
reagents
P
S
N
Li
organolithium
reagents
CH2
Ph
Cu
R Li
O
C
C
dithiane anion
Na
B
H
Use "D" versions of hydrides
as marker of reaction site.
H
cyanoborohydride
Examples of carbon electrophiles in our course.
O
O
O
O
O
O
O
O
R
Br
H
H
methanal
R
R
O
O
O
R
R
bromoalkanes
R
H
aldehydes
R
ketones
O
O
R
O
anhydrides
R
R
R
bromoalkanes
SH
NH2
R
R
R
1o amines
alcohols
R
terminal
alkynes
nitriles
O
carboxylic
acids
R
O
R
H
R
H
R
carbonyl compounds,
and nitriles
O
O
C
R
thiols
N
amides
(1o,2o,3o)
O
carbon dioxide
,-unsaturated
ketones
O
N
OH
R
R
C
nitriles
Single functional group molecules
O
O
N
C
epoxides
Br
R
Cl
R
acid chlorides esters
R
O
H
aldehydes
R
O
carboxylic
acids
R
R
Cl
acid chlorides
R
NH2
1o amides
aromatics
alkenes
Combination functional group molecules
O
H
R2
O
R2
R1
R1
R1
O
O
R2
R1
R1
N
R2 R1
N
R2
R1
R2
R2
R1
O
R1
OH
OH
O
O
R2
R1
R2
R1
O
O
O
R2
R1
S
R2
R3
N
H
R1
N
R1
R2
R2
R1
R1
R2
R2
R3
C1, C2, C3
know the reactions of these carbon skeletons,
many examples are provided in the "Courses" web page link on
Chem 315 C1,C2, C3 synthesis.
C4 =
C5 =
C6 =
C7 =
(1+3) (2+2) (1+1+2) (1+1+1+1)
(1+4) (2+3) (1+1+3) (1+2+2) (etc.)
(1+5) (2+4) (3+3) (1+1+4) (1+2+3) (2+2+2) (etc.)
(1+6) (2+5) (3+4) (1+1+5) (1+2+4) (2+2+3) (etc.)
R3
R2
34 The following examples are presented without full details. Possible structures to accomplish a transformation are
provided, assuming that you can deduce the nucleophile and the electrophiles from the context given. It is also assumed
that you are familiar with the C1, C2 and C3 example reactions at the start of this topic and once a precursor of that size
is reached, no further details are given. If that is not the case, you need to review the above material so that you can
make the necessary connections to see the ‘logic’ of the proposed approaches. Once a structure is prepared, it is used
without resynthesizing it. Dashed lines are drawn to show nucleophile/electrophiles disconnections. Finally, there may
be several acceptable approaches, but due to limited space and time only one or a couple are given.
Functional Group Target Molecules (single and multiple carbon skeletons)
Thiols
1o amines
Nitriles
Aldehydes
O
OH
O
Br
H
O
CH2
O
OH
O
H
HO
CH2
Br
Br
35 Carboxylic acids
,β-unsaturated C=O
O
O
O
OH
Ph
S
H
O
Ph
CH2
CH3
Ph
Ph
O
OH
Br
S
Br
mCPBA
Alkenes
Ph
Br
CH2
P
O
O
OH
Ph
CH2
Ph
Ph
P
H
CH2
Ph
HO
Br
O
HO
O
Ph
Cuprate RBr/RBr coupling
Cuprate conjugate addition (and some ketone syntheses)
O
O
Li
Li
Br
Cu
Li
Li
O
O
Br
Cu
Li
Li
O
O
Cu
Br
N
CN
Br
Br
OH
2
CH3
Acid chlorides
O
H3C
Br
Br
CH3
Li
O
O
2
O
C
Br
O
Cl
Li
OH
H 3C
Cu
CH3 Cl
Li
OH
Cu
2
Li
36 1o Amides
CN
O
O
NH2
Cl
O
Br
OH
CO2
Br
OTs
OH
O
H
O
O
Cl
O
NH2
OH
CO2
OH
OTs
Br
CN
Cuprate couplings
O
Br
Li
H
*
Cu
Br
2
HO
TsO
Br
Br
Li
Li
Br
2
Cu
TsO
Li
O
O
O
OH
Br
Br
O
Br
OH
HO
H
Epoxides by sulfur ylid
O
OH
O
O
Ph
S
CH2
O
Ph
Ph
S
S
Ph
Ph
H
Ph
Alkyne variations
OH
OH
O
O
Br
H
Br
37 alkynes at a branch point - use the a variation of the Wittig reaction
O
O
O
O
O
O
P
H
P
H
OMe
OMe
OMe
OMe
N2
N2
Ethers
O
Br
CH3
Br
HO
CH3
SN1
S N2
Br
OH
OH
S N2
O
SN 1
HO
Br
Sulfides
SH
Br
OH
S
Br
Br
O
TsO
HO
H
SH
Br
Br
O
Br
o
Br
O
OH
S
o
O
HO
CH2
Br
o
1 ,2 ,3 amines
H
N
N
O
O
Br
N3
H2N
CH2
Br
O
N
OH
O
H
N
H
O
OH
NH2
N3
Br
38 Esters
O
O
O
Br
OH
O
OH
Br
Br
CO2
O
O
O
OH
Br
O
O
OTs
CO2
Br
OH
OTs
Br
OH
Cl
O
H
O
HO
Br
CH2
O
O
O
Br
OH
Br
O
OH
Ketones
O
O
O
2
2
Cl
OH
Li
Li
2
O
2
Br NC
Cu
Br
O
Cu
Br
HO
2
CN Br
Cl
Li
Li
O
OH
O
Br
H
OH
O
CH2
Br
39 Alcohols
OH
OH
O
Br
O
Br
H
Br
H
O
Br
OH
O
OH
OH
O
OH
H
OH
Br
OH
2
O
OH
Mg
CH3
O
CH3
O
OH
Br
Br
Br
O
O
Br
OH
Anhydrides
O
O
O
O
H
O
Cl
HO
O
O
O
OH
H
CH3
OH
OH
O
O
O
O
CO2
Br
OH
Cl
CO2
Br
HO
1o,2o,3o amides
O
O
O
Cl
OH
N
H
OH
H 2N
O
O
N
Br
N3
O
Cl
OH
O
Br
OH
O
HN
H2N
N3
Br
40 Alkenes by Wittig
Ph
H
Ph
Ph
Ph
Ph
Ph
O
Br
Ph
P
Ph
Br
Br
Ph
HO
H
Ph
Br
Ph
P
P
P
Ph
Br
Ph
Ph
Ph
Ph
Ph
Ph
P
P
H
Ph
Ph
Ph
O
P
P
P
O
Ph
Ph
Ph
Ph
Br
Ph
Ph
Br
O
CH2
41 anti-Markovnikov addition
syn addition
anti-Markovnikov addition
anti addition, SN1-like
anti addition
same as 1, but no rearrangement
syn addition
rearrangement possible
anti + backside = syn
no rearrangement
anti addition, SN2-like
Br
1. NaH
2.
NaSH
Br
1. NaOH
2.
H2NNH2
RO / 
1. NaH
2.
OH
1. NaN3
2. LiAlH4
3. workup
1. BH3
2. H2O2, HO
1. n-BuLi
2.
Br
1. BH3
2. Br2, CH3O
1. O3, -78oC
2. CH3SCH3
O
K
Br
OH
1. NaBH4
2. workup
or
1. LiAlH4
2. workup
HBr
ROOR
h
1. O3, -78oC
2. NaBH4
TsOH (-H2O)
HO
OH
H2SO4
H2O
O
TsOH
1. HgX2 / H2O
2. NaBH4
Br2
1. mCPBA
2. CH3OH+ / CH3OH
Br
2
HO
Br
HO
Br
CH2
syn addition
mCPBA
O
Cl
Br
O
O
HBr
H2SO4
H2O
HBr
ROOR
h
O
K
Br2
h
1. CH3CO2 Na
2. NaOH
1. Mg
2. O
1. BH3
2. H2O2, HO
TsOH (-H2O)
TsOH (-H2O)
OsO4
NaOH
1. Mg
2. O
H
3. workup
3. workup
KMnO4
NaOH
H2SO4

1. Mg
2. CO2
3. workup
diastereomers
O
Ph
Ph P CH2
Ph Cl
1. n-BuLi
Ph
2.
Ph P CH3
Ph Br
O
N2
H2SO4
H2O
Br2
OH
CH3
OH
H
CH3
H
H3O+
H2O
H
H
OH
O
H
deprotect aldehydes and ketones
O
O
1. BH3
2. Br2,
CH3O
not
discussed
1. O3 / -78oC
2. H2O2 / HO
O
O
1. HgX2,
H2O
2. NaBH4
O
Pd / D2
quinoline
1. O3 / -78oC
2. CH3SCH3
O
Br
MeO
O
CH3
Br
1. 3 eqs.
NaNR2
2. workup
MeO
Br2
H2O
CrO3
H2O
CH3
H3O+
H2O
1. RO
2. H
1. NaBH4
2. workkup
H
OH
meso
P
OH
OH
enantiomers
O
1. Br2 / H2O
2. NaOH
H
O O
Br
OH
no rearrangement
Markovnikov addition
Br
Br2
H2O
Br
no rearrangement
anti addition
OH
1. mCPBA
2. CH3O / CH3OH
2 eqs.
Br2
h
HBr
anti-Markovnikov addition
O
1. O3, -78oC
2. H2O2 / HO
O
1. BH3
2. Br2, CH3O
Br
O
3. workup
1. NaOH
2.
Br
3. NaOH
4. workup
Br
1a
cuts C=C, makes two alcohols
cuts C=C, makes acids and ketones
can make
epoxides
OH
NaOH
Br2
h
O
cuts C=C, makes aldehydes and ketones
can make
alkynes
OH
CH3
deprotect alcohols
Na / NH3
ROH
Pd / H2
o
1. O3 / -78 C
2. NaBH4
1. Br2
H2O
2. NaOH
Pd / D2
1. mCPBA
2. H3O+/H2O
or
1. mCPBA
2. HO /H2O