Initials: _______
Chemistry 634, Fall 2014
Midterm 2
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Closed note, closed book. No calculators allowed. You may use a molecular model
set.
Answers must be written in the spaces or boxes provided. Other markings will not be
considered.
Please initial each page at the top.
Points will only be awarded for clearly communicated answers.
There are 9 total pages to this exam. The last 2 pages were intentionally left blank
and may be used for scratch paper. Please be sure your copy has 9 pages before
you begin.
Name: __________________________________________________
Problem
Points
1
_____/56
2
_____/18
3
_____/16
4
_____/25
5
_____/35
6
_____/20
7
_____/30
TOTAL
_____/200
1
Initials: _______
Liu and co-workers published a synthesis of N-deoxymilitarione A earlier this year (Org.
Lett. 2014, 16, 26). Their synthesis utilizes many of the methods we’ve discussed so far
in class. This test focuses on their synthesis.
HO
OH O
CH3
OH
N
H
O
CH3 CH3 CH3
N-deoxymilitarione A
2
Initials: _______
1. (56 points) The authors build part of their target molecules using the strategy shown
below. Please provide the missing reagents and intermediates. In some cases, more
than one step may be required.
O
O
O
O
NH
O
Bn
N
CH3
Bn
O
O
O
O
O
*
N
O
CH3
CH3
O
O
Bn
Bu2BOTf, Et3N
OH
* * *
N
Bn
CH3
CH3
Bn
1
O
*
H
HO
CH3
*
*
CH3
N
O
CH3
(COCl)2, DMSO;
then Et3N
CH3 CH3
CH3 CH3
2
O
EtO P
EtO
1. DIBAl-H
2. (COCl)2, DMSO;
then Et3N
CO2Et
CH3
NaH
O
*
*
CH3 CH3 CH3
CH3
EtO2C
*
*
CH3
CH3 CH3 CH3
3
3
Initials: _______
2. (18 points) Via the scheme shown in Problem 1, three vicinal stereocenters are
formed. These stereocenters are marked with an asterisk (*) in compound 2. Please
indicate the expected stereochemistry for compound 2 by filling in the missing bonds
below as wedges or hashes.
O
O
O
OH
N
CH3
Bn
CH3 CH3
2
3. (16 points) Using clearly drawn pictures, rationalize your predicted stereochemistry in
the formation of 1 in the scheme shown in Problem 1.
4. (25 points) Using clearly drawn pictures, rationalize your predicted stereochemistry in
the formation of 2 in the scheme shown in Problem 1.
4
Initials: _______
5. (35 points) (a) Please draw a reasonable arrow-pushing mechanism for the formation
of 3 (in the scheme shown in Problem 1).
(b) Using clearly drawn pictures, rationalize the observed olefin geometry in the
formation of 3.
5
Initials: _______
6. (20 points) For the other part of their target, the authors make pyridine 6. They
observe good selectivity for the syn product (6, isolated after aqueous work-up) in the
addition of aryl lithium 4 to cyclohexanone 5. Using clearly drawn pictures, rationalize
the observed stereochemistry in this reaction.
O
OMOM
OLi
Li
Me
N
OMOM
4
TBSO
OMOM
OH
+
Me
OH
OTBS
5
N
OMOM
6, 44%
syn/anti = 10:1
6
Initials: _______
7. (30 points) To finish their synthesis, the authors connect the 2 pieces. Please provide
the missing reagents for each of the following transformations. In some cases, more
than one step may be required.
TBSO
TBSO
OMOM
OH
Me
OH
3
OMOM
O
N
N
OMOM
TBSO
OMOM
OMOM
O
CH3
OH
CH3
O
Me
OH
N
CH3 CH3 CH3
HO
OMOM
CH3 CH3 CH3
OH O
(single step)
CH3
OH
N
H
O
CH3 CH3 CH3
N-deoxymilitarione A
7
Initials: _______
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8
Initials: _______
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9