Problem Set 12
1. (a) Provide a mechanism for the conversion of 3 equivalents of formaldehyde to
glyceraldehydes (in base) using a catalytic amount of glycolaldehyde (shown).
O
HO
O
3
H
H
OH
H
HO
H
formaldehyde
glyceraldehyde
O
HO
O
H
O
HO
H
HO
H
H
OH
O
catalytic
glycolaldehyde
H
O
O
HO
H
H
HO
H OH
H
OH
O
O
HO H
H
H
HO
OH
HO
HO
O
H
HO
H
O
HO
O
HO
HO
HO
OH
OH
OH
HO H
OH
O
OH
H
OH
HO H
HO
HO
HO H
HO
O
HO
O
OH
OH
O
HO
O
H
HO
HO
O
OH
OH
H
O
OH
H
O
O
H
HO
H
OH
HO
HO
O
OH
HO
OH
H
O
O
(b) Provide a mechanism for the conversion of 2-methyl-2-cyclohexenone to all
possible tautomers in acidic media. (Hint: there are four of them).
OH
HO H
O
H3C
OH
H3C
H OH
OH
O
H3C
H
H
O
H
O
H3C
OH
H3C
HO H
H OH
O
OH
OH
O
H3C
H3C
H3C
H3C
(c) Draw the deuterated compound obtained when 2-methyl-2-cyclohexenone is
dissolved in a large excess of CH3OD containing base, and recovered.
O
H3C
D
D
D D
(d) Provide all the possible tautomers of 3-methylenecyclohexenone. (Hint: there
are seven of them) (21 pts).
O
OH
O
OH
OH
O
OH
3-methylenecyclohexanone
OH
(e) Draw the deuterated compound obtained when 3-methylenecyclohexenone is
dissolved in a large excess of CH3OD containing base, and recovered. (8 pts).
O
D
D
D
D
D
D D
D
(f) Provide the structures of the four possible tautomers of naphthalene-1,3-(2H,4H)dione.
A:
O
O
naphthalene-1,3
(2H,4H)-dione
B:
O
OH
OH
C:
OH
D:
O
OH
OH
O
(g) State which of these tautomers is the most stable (i.e. would predominate at
equilibrium) and explain your reasoning.
OH
aromatic
OH
2. Provide a curved arrow mechanism for the following transformations. It is far more
important that you propose reasonable mechanistic steps than that you get all the
way to the product. Don't ignore resonance forms—they can lead the way!
(a)
O
O
–
H
2
C
OH
N
(cat.)
N
HB
O
O
H
N
O
OH
H
O
B
N
(b)
OMe
H
O
H
H
OMe
O
O
H3O+
OMe
OMe
OMe
OH
OH
H
OH
O
H
OH
H
O
H
H
H
O
H
H
(c)
O
O
OCH3
O
(CH3)2CuLi
O
OCH3
C C
H3C
CH3
OCH3
Cu
CH3
O
O OCH3O
OCH3
O
OCH3
C C
CH3
OCH3
CH3
OMe
(d)
O
H
O
O
NaOEt
H
EtO
OEt
H
O
CO2Et
HOEt
CO2Et
OEt
O
HO H
O
CO2Et
H
EtO
OEt
EtO
EtO
H
HO H
O H
H
CO2Et
CO2Et
H
CO2Et
EtO
O
(e)
O
O
CHO
HCl
MeOH
O
(f)
O
O
OEt
O
O
O
H
CH3
O
O
O
OCH3
NaOCH3
OCH3
CH3OH
O
O
O
OCH3
OCH3
CH3
O
O
O
OH
O
OCH3
OCH3
O
H3CO H
O
O
H
OH
O
O
OCH3
OCH3
O
H
OCH3
O
H OCH3
O
O
O
OCH3
O
3. The natural product alternariol is biosynthesized (made by Nature) from simple
heptaketide fatty acid 1 [JCS Chem. Commun. 1972, 953]. Provide a retrosynthetic
analysis of alternariol accounting for its formation from 1. (HINT: Start by
hydrolyzing the ester, and don't forget about keto/enol equilibria!!!)
OH
O
O
O
O
O
O
enzymes
O
CH3
OH
OH
HO
1
O
O
Alternariol
OH
OH
CH3
OH
HO
CH3
hydrolyze
O
OH ketos to enols
COOH
ester
O
HO
OH
O
O
CH3
O
CH3
hydration
O
COOH
O
OH COOH
O
O
hydration
COOH
O
HO
CH3 O
O
O
O
O
O
O
O
O
OH
1
O
O
COOH
O
O
reverse aldol
reverse aldol
O
O
O
CH3 O
convert all
4. In a synthesis of the terpene longifolene, the tricyclic intermediate D was obtained
from a bicyclic intermediate by an intramolecular Michael addition. Deduce the
possible structure of all possible bicyclic precursors. Suggest which you think was
the actual one used and explain your reasoning.
H3C
O
O
CH3
D
H3C
H3C
O
H3C
O
H3C
O
O
O
O
O
O
CH3
CH3
CH3
CH3
A
B
anti-Bredt
C
D
reasonable fused 6/7
ring system
pentavalent carbon
O
O
O
Michael
aldol
O
O
O
D
DIBAL
Although not the actual route
used to D in the literature, this
is a retrosynthesis based on
standard synthons.
O
O
NaCN
CN
O
5.
(a) Provide a mechanism for the following transformation in basic media.
H
O
H
OH
HO
–OH
H
H
OH
H
OH
H
O
H
OH
O
HOCH2
CH2OH
Dihydroxyacetone
D-Glyceraldehyde
CH2OH
CH2OH
D-Glucose
(b) Provide a detailed mechanism to account for the conversion of D-fructose into
two equivalents of pyruvaldehyde. (Hint: glyceraldehyde will be an intermediate.)
OH
O
HO
H
H
OH
H
OH
CH2OH
–OH
O
O
H
Pyruvaldehyde
D-Fructose
(c) Provide a detailed mechanism to account for the conversion of 3 equivalents of
glycal into an aldohexose. Ignore stereochemistry. (18 pts)
OH OH
O
–OH
O
3
HO
HO
H
Glycal
OH
OH
Aldohexose
H
6. (a) Provide the two different keto forms in equilibrium with the enol form below:
OH
OH
O
ENOL FORM
O
OH
OH
O
O
O
KETO FORM A
KETO FORM B
(b) Provide mechanisms for the conversion of the enol form to both keto forms
under basic conditions:
O
H OH
–OH
OH
OH
OH
O
O
OH
O
O
–OH
HO H
OH
O
OH
O
O
O
(c) Provide mechanisms for the conversion of both keto forms to the enol form under
basic conditions:
7. Provide a detailed mechanism to account for the following reaction.
CH3
O
–OH
O
H
O
C
H2
CH3
H2C
CH3
H OH
O
O
O
O
CH3
H3C
HO H
O
O
O
O
H3C
O
O
H
–OH