Initials: _______
Chemistry 634, Fall 2014
Midterm 2
•
•
•
•
•
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 10 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 10 pages before
you begin.
Name: __________________________________________________
Problem
Points
1
_____/64
2
_____/56
3
_____/80
TOTAL
_____/200
1
Initials: _______
1. (64 points) The Baran group recently completed a synthesis of (+)-Ingenol (J. Am.
Chem. Soc. 2014, 136, 5799).
(a) Please provide the missing reagents for each of the following transformations. For
each box, only one step is required.
Cl
Cl
Me
Me
Me
Me
O
Me
Me
Me
O
1
Me
Me
Me
O
H
OH
Me
2
Me
Me
Me
HO
H
OH
Me
3
2
Initials: _______
(1 – continued)
(b) Using clearly drawn pictures, rationalize the observed stereochemistry in the
formation of 2 from 1 in (a) above.
(c) Using clearly drawn pictures, rationalize the observed stereochemistry in the
formation of 3 from 2 in (a) above.
3
Initials: _______
2. (56 points) The Sherburn group recently published their strategy for the framework of
nicandrenone (Org. Lett. 2015, ASAP).
(a) Please fill in the missing structures and reagents in the following scheme.
PPh 3Br
O
n-BuLi, LiCl; then 4
O
MeO 2C
4
O
N
MeO 2C
N
O
LiCl, DBU
O
DBU (base)
MeO 2C
5
4
Initials: _______
(2 – continued)
(b) Using clearly drawn pictures, rationalize the observed olefin geometry in the
formation of 5.
(c) Please propose a synthesis of aldehyde 7 from alcohol 6.
O
OH
MeO 2C
6
7
5
Initials: _______
3. (80 points) The following problem is from Suh’s recent synthesis of (–)-Galiellalactone
(J. Org. Chem. 2015, ASAP).
(a) Please draw a reasonable arrow-pushing mechanism for the following reaction.
OCO2Et
O
PhO 2S
cat. Pd(OAc) 2, dppf
O
O
OTBS
SO2Ph
H
PPh 2
O
8
Fe
PPh 2
9
OTBS
dppf
6
Initials: _______
(3 – continued)
(b) Please fill in the missing reagents and structures in the boxes below. In some cases,
more than one step may be required.
HO
H
H
O
HO
H
O
HO
OTBS
MnO 2
H
H
HO
OH
H
O
O
MesN
O
OH
O
O
Me
OH
H
Cl
O
Cl
Ph
PCy 3 (cat.)
O
H
O
H
Me
OH
NMes
Ru
OTES
H
H
Me
OTES
H
OH
H
O
O
H
O
H
7
Initials: _______
(3 – continued)
(c) Please draw a reasonable arrow-pushing mechanism for the transformation of 10 to
11.
MesN
Me
OH
O
NMes
Ru
OTES
H
Cl
Me
Cl
Ph
PCy 3 (cat.)
OH
OTES
H
O
O
H
10
O
H
11
8
Initials: _______
This page has intentionally been left blank, so that you may use it for scratch paper.
9
Initials: _______
This page has intentionally been left blank, so that you may use it for scratch paper.
10