Chem 206 Due: Friday, Dec.
Problem Set 9 Name:_____________ TF:_______________
General Instructions: Neatly, in the space allocated, provide concise answers to the following questions using
clear three-dimensional representations for all relevant structures. Address stereochemical and stereoelectronic
issues where appropriate.
Question 1.
The reaction illustrated below was recently reported by Murry and co-workers from the Merck Process
Group. Provide a mechanism for this transformation in the space below.
Tol Ar2 O
O SO2 O 10 mol% 1 S
I
+ Ar1
N OCMe3 Me N CH2CH2OH
Ar1 H Ar2 N OCMe3 Et3N, CH2Cl2 H
H O 1 (used as catalyst)
35 °C
Question 2.
The Von Richter reaction is illustrated in the Br Br
accompanying equation. Please provide a plausible
mechanism for this transformation taking into account the KCN
following observations. (a) If 15N-labeled KCN is used, the + N2
heat,
N2 formed is half labeled; (b) 3-bromo-benzonitrile does aqueous EtOH CO2H
not form 3-bromo-benzoic acid under the reaction
NO2
conditions.
Provide your answer in the space below:
Question 3.
Padwa reported the interesting transformation shown below. Provide a detailed mechanism and identify any
organic named reactions in this sequence.
O Et
S O
Ac2O CO2Me
O
TsOH MeO N O
MeO N
O CO2Me MeO
MeO
ANSWER:
Question 4.
Fishli and Branca have reported the annulation reaction sequence shown below.
Me O
KOt-Bu
O
Me
SO2Ar
Provide a detailed mechanism for this transformation in the space below.
Question 5.
Trost and Adams have reported the interesting spiroannulation reaction sequence shown below. In the first
step the enolate alkylation produces a single diastereomeric adduct A. Rearrangement of A under Lewis
acidic conditions affords a mixture of B and C. As the reaction times are increased more C is produced by
equilibration.
Me O
O O
base Et2AlCl Me Me
SO2Ph A
Me
Me3Si OSO2Me
B C
Part A. Using your knowledge of the conformations of eight-membered rings, predict the stereochemical
outcome of the the alkylation and identify the full stereostructure of A.
Part B. Provide a detailed mechanism for the transformation of A into B in the space below.
Question 6.
The fumagillin natural products possess several interesting biological O
properties including antibiotic activity against Staphylococcus auereus. Me Me
In Sorensen's recent synthesis of fumagillol, intermediate 1 was
transformed into its a-oxygenated counterpart 3 through the indicated Me
reaction sequence. OMeO
RO H
fumagillol
CHO Me Me X H
Me Me
AcO
Me acetyl chloride
RNH–OH Me
1 A
–H2O Et3N
O 2 X = NR
O H3 O +
O Me 3 X=O
O Me
Me
Me
In the space below, identify the structure of intermediate A and provide a mechanism for the transformation
of 1 into 2.
Question 7.
Here is a good exercise that deals with the verstility of the nitro group. Provide a detailed mechanism for the
following reaction.
Ph
Ph excess Me
Me Me MeNHNH2/MeNHNH3Cl
N Me
N
NO2 NO2
Me
Answer
Question 8.
S. Zard has recently reported the very clever synthesis of acetylenes from β-keto esters illustrated below. In this
article, he demonstrates that this transformation exhibits broad scope.
O O
NH2OH Intermediate HOAc, NaNO2
R OEt 1 R R"
–EtOH, H2O –CO2, N2O
R"
Provide a plausible mechanism for this transformation and identify intermediate 1 in the space below.
Question 9.
Hoye et al. studied the following silylative cyclization in the context of a
construction of the telomerase inhibitor UCS1025A.
Part A: Rationalize the mechanism and explain the diastereoselectivity O H H
O O H
O
TMSOTf,
Et3N N N
N Me
CDCl3, rt O
OTMS
MeO2C O OH
CO2Me
O
88%, dr 62:1 UCS1025A
Part B: The seemingly similar starting material derived from L-malic acid showed a different reaction course.
Knowing about the outcome, you can definitely provide a good a posteriori explanation!
O
O
TMSOTf,
Et3N N quant., 90% pure
N (rac)- by 1H-NMR
O
CDCl3, rt OTMS (unstable on silica)
OH
MeO2C O OTMS
MeO
