Iverson CH 320N KRE Table: For use in synthesis problems, count carbons in products and starting materials then

identify location(s) of new bonds,

especially C-C or C=C bonds. With that information, use the following KREs to determine which reactions are appropriate.
O

KRE: An imine indicates an New bond H 2N New C-C bond

N
New C-C bond MgBr aldehyde or ketone reacting H O O O
O with a primary amine or
KRE: A new C-C bond two 1) ph 4.0
or ammonia KRE: This is a cyclic β-ketoester β 1) 1.0 eq. NaOEt
carbons away from an -OH H α O
group indicates an OH CuLi that indicates a Dieckmann reaction 6 1 (or LDA) 6 5 4
3
2 1
5 2 O O
organometallic reacting starting with a 6-carbon diester. *
2) H3O (mild) 2 Notice that Dieckman reactions 4 3
with an epoxide. or
Fischer O require 1.0 equivalent of base. Racemic 2) H3O (mild) O
Li HO
esterification
O H2SO4 (catalytic)
New bond OH
O KRE: Ester group O 1) 1.0 eq. NaOEt
New C-C bond New C-C (or LDA)
O KRE: This is a nucleophile O O
HO O bond O
KRE: A new C-C bond on 1) linked to the β-carbon of β
O
the same carbon as a H MgBr the amide. This is also a β α
Cl 2)
secondary -OH group methyl ketone. Putting α NH2
* O
indicates a Grignard Racemic these together indicates a NH2
2) H3O (mild) New bond
reacting with an aldehyde. OH Michael reaction starting 3) H3O (strong) and heat
KRE: This is a lactone (cyclic O O O with acetoester
O ester). The six-membered ring H2SO4 (catalytic)
New C-C bond 5 1
New C-C
indicates a 5-carbon hydroxy acid 4 2
5 3 O O
KRE: A new C-C bond on 1) starting material that undergoes 4 2 HO 1 OH bond
MgBr 3 O
the same carbon as a Fischer esterification. 1) 1.0 eq. NaOEt
tertiary -OH group indicates KRE: Reaction of a β (or LDA)
a Grignard reacting with a O nucleophile (β-diketone) O
2) H3O (mild) α O
ketone. OH connected to the β-carbon β
of a carbonyl (the ester) 2) α
O
New C-C bond Cl O
2 H 2N 3) H3O (mild) O
KRE: A new C-C bond on 1) CO2 or O O
MgBr O
on a carboxylic acid in O New bond
which one carbon atom was KRE: Amide group
added indicates a Grignard 2) H3O (mild) O O
N 1) 1.0 eq. LDA
reacting with CO2. OH H O
O New C-C bond 2) Br α
H 2N
New C-C bond
O KRE: alkylated ketone deriving Or
from either an enolate made with α *
N
O LDA or using an enamine
KRE: A new C-C bond Racemic
from a CN on the same C OH HCN O 1) Br N
carbon as an -OH group Racemic New C-C α
* KRE: Two identical new C- OH 2) H3O (mild)
indicates HCN reacting bond 1)
with a ketone or aldehyde. C bonds on the same carbon O
as a tertiary -OH group 2 MgBr
indicates two equivalents of
a Grignard reacting with an 2) H3O (mild)
New C-C bond New C-C bond
ester. New C-C 1) 1.0 eq. LDA O
bond O O O 2) O
O New C-C Cl α
KRE: A new C-C bond 1) KRE: A ketone with an new O bond KRE: A β-diketone α
from an alkyne on the same OH 1) β
C-C adjacent to the Cl CuLi indicates reaction of an acid
carbon as an -OH group Racemic * Or
* carbonyl indicates an acid chloride with either an
O
indicates an alkyne anion chloride reacting with a 2 enolate made with LDA or
2) H3O (mild) 2) H3O (mild)
reacting with a ketone or Gilman reagent. using an enamine 1) Cl
N
aldehyde. Racemic
α
2) H3O (mild)
New C-C bond
New C=C bond O α
KRE: An β-hydroxy aldehyde with H
an indicates an aldol reaction with NaOH (catalytic)
P(Ph)3 α 1) 1.0 eq. NaOEt
KRE: A new Z C=C bond H no dehydration. H
O
* * (or LDA) O O
indicates an alkyl Wittig β O New C-C bond
reagent was used. Z alkene 2)
Br
Racemic OH O KRE: A methyl ketone with α α
substitution at the α-carbon * O
indicates an acetoester synthesis. 3) 1.0 eq. NaOEt
O New C-C
The second new C-C bond (or LDA)
bond
New C-C bond O O indicates a second alkylation with 4) CH3Br
Racemic
KRE: A new E C=C bond CH3Br
indicates a Wittig reagent H New C=C bond 5) H3O (strong) and heat
P(Ph)3 α
with a carbonyl adjacent to H
the negative charge (enolate α
Wittig) was used. E alkene KRE: An α,β-unsaturated E,Z Mixture 1) NaOH (catalytic) H
aldehyde with an E.Z mixture O New C-C bond
O
New bond New bond indicates an aldol reaction 1) 1.0 eq. NaOEt O O
O KRE: A carboxylic acid with
followed by dehydration in 2) H3O (mild) and heat O (or LDA)
α substitution at the α-carbon α
H3CO OCH3 CH3OH acid. H indicates a malonic ester
KRE: An acetal where a HO O O
synthesis. α 2) Br
carbonyl used to be H
indicates acetal formation H H2SO4 (catalytic) 3) H3O (strong) and heat
New C=C
with an alcohol. O
bond
O
O New C-C bond 1) 0.5 eq. NaOEt
OH New C-C bond O
KRE: This is a very tricky one. A (or LDA) α
KRE: A five or six- New bond HO β O α O
O New bond KRE: This is an α,β-unsaturated 1) NaOH (catalytic) symmetric ketone indicates a Claisen
membered ring cyclic acetal O H 6 α reaction followed by ester hydrolysis
aldehyde that indicates an aldol 1 H 2) H3O (strong)
where a carbonyl used to be H2SO4 (catalytic) 5 2 H
reaction followed by dehydration. In 5 3 1 and decarboxylation of the resulting β- O and heat
indicates acetal formation H 4 3 2) H3O (mild) H 6 4 2
keto ester.
this case the ring is formed because a
with a two or three carbon and heat
6-carbon dialdehyde is used.
diol. O
New bond O
O
New C-C bond
O OH O CH3 O
KRE: A five or six-membered New C-C bond 7 9 CH3
H2SO4 (catalytic) O KRE: A new six- 8
ring cyclic hemiacetal indicates 4 5 1 * 3 7 3
4 * 1) 0.5 eq. NaOEt membered ring with 2 *
10
2
3 2 β O 4 8 4
or 5-carbon hydroxyaldehyde 4 2 HO 5 1 H KRE: A β-ketoester indicates a α (or LDA) two new C-C bonds
starting material. 3 Racemic α 5 1 5 1
Claisen reaction. and an α,β-unsaturated 10 9
O 6 Catalytic NaOH 6
Racemic 2) H3O (mild) ketone indicates a O O
O O Racemic and heat
Robinson Annulation
reaction. New C-C bond