1

Last Name (print) _____________________________________________________ CHEM 345
First Name (print) _____________________________________________________ Summer 2024
UW email: ___________________________________________________________ Exam 3
I. Explore the example crossed aldol reaction of acetone and para-nitrobenzaldehyde provided below by
addressing the prompts that follow. (30 pts)
A. Predict the possible products of a crossed aldol reaction and a crossed condensation reaction in the
boxes above. (4 pts)

B. Provide a complete electron-pushing mechanism for the formation of the nucleophile that leads to
the aldol addition product(s) in the system described above. Clearly show all lone pairs, formal
charges, and the important resonance structures of the nucleophile that indicate which atoms are
nucleophilic. (4 pts)










C. There are two carbonyl-containing compounds in the reaction mixture that could potentially react
with a nucleophile. Identify the most electrophilic carbonyl-containing compound and rationalize its
electrophilicity. (2 pts)
2
D. Provide a complete electron-pushing mechanism leading to the addition and condensation
products that would result from treating acetone and para-nitrobenzaldehyde with
aqueous sodium hydroxide (shown below). Clearly show all lone pairs, formal charges,
resonance structures etc... Make sure that your mechanism is consistent with a reaction
which is under thermodynamic control. (8 pts)



































3
A chiral base such as (S)-proline can be used to catalyze an aldol reaction in an enantioselective
fashion. The accompanying spectra are from the product of this reaction; use them to
determine the major and minor product when the reaction is carried out in this manner.



E. Identify in the major product the hybridization of the 13C-atom(s) responsible for each signal and
any key functional groups. Note that only the signals associated with the major product have
been peak picked here. (6 pts)











4
F. Using your chemical knowledge of crossed aldol reactions, identify the major and minor
product of the reaction based upon the authentic 1H- NMR spectrum of the product mixture
provided below. Hint: Which product seems more likely based upon the 13C-NMR? For the
major product, assign each of the labeled 1H-NMR signals to its corresponding 1H-atom in
the molecule. (7 pts)













Page 5 of 8
II. Phenyl isocyanate and substituted phenyl isocyanates (boxed below) are important
precursors to many biologically active carbamate esters. An example synthesis leading to a
class of anti-fungal and HIV-1 RT inhibiting molecules is shown below. Bioorg. Chem. 2016,
64, 66-73.












A) In the space below, provide electron-pushing mechanism for the reduction step 1 with NaBD4 in
dry MeOH. Be sure to show all appropriate arrows, lone pairs, formal charges, stereoisomers,
intermediates and final product(s) etc. (12 pts)


























Page 6 of 8
B) Phenyl isocyanates and substituted phenyl isocyanates can be synthesized effectively from
benzoic acid derivatives. Provide the missing reagents for the first step below and provide an
electron-pushing mechanism for steps 2 and 3 only. Be sure to show all appropriate arrows,
lone pairs, formal charges, intermediates, etc. (12 pts)
Page 7 of 8
III. Predict the major product(s) of the following reactions or provide the reagents necessary to affect the
chemical transformation shown. Explicitly show all stereochemical outcomes and lone electron pairs.
(24 pts total)



A.


Explain stereochemical outcome of this reaction.







C.
Explain the stereochemistry of the product(s).










D.

Why is an intramolecular reaction faster than an intermolecular reaction in this case?

Page 8 of 8

IV. Provide a reasonable synthesis of 1,5-bis(4-methylphenyl)-1,4-pentadien-3-one utilizing p-
bromotoluene and acetone. You do not need to give a mechanism for the individual steps.
Show all isolated intermediates/products formed and lone electron pairs. (16 pts total)




学霸联盟