398 CHAPTER 8 Alkenes: Structure and Preparation via Elimination Reactions

8.11 IDENTIFYING THE EXPECTED MECHANISM(S)

EXAMPLE Identify STEP 1 Identify STEP 2 Identify the substrate

the mechanism(s) the function of and determine the mechanisms
expected to occur. the reagent. that operate.
1° E2 + SN2

Br @ Minor Major
OEt
Strong Strong
2° E2 + SN2
Strong Nuc Nuc Base
NaOEt
? Strong base
Examples: RO
@
HO
@
Major Minor

3° E2

Try Problems 8.41–8.45, 8.68, 8.69, 8.78a

8.12 PREDICTING THE PRODUCTS OF SUBSTITUTION AND ELIMINATION REACTIONS

STEP 1 Determine the STEP 2 Analyze the substrate STEP 3 Consider any relevant
function of the reagent and determine the expected regiochemical and
(Section 8.12). mechanism(s) stereochemical requirements
(Section 8.13). (Section 8.14).

Try Problems 8.46–8.49, 8.77, 8.79

PRACTICE PROBLEMS Note: Most of the Problems are available within

an online teaching and learning solution.
,

8.50 Assign a systematic (IUPAC) name for each of the following 8.54 For each pair of compounds identify which compound would
compounds: react more rapidly in an E1 reaction:

Cl Cl
Cl

(a) (b) (c) Cl

(a) (b)
8.51 Using E-Z designators, identify the configuration of each CRC
double bond in the following compound: 8.55 Identify the stronger base:
Br Cl (a) NaOH vs. H2O
(b) Sodium ethoxide vs. ethanol
O
8.56 (2S,3S)-2-Bromo-3-phenylbutane undergoes an E2 reaction when
treated with a strong base to produce (E)-2-phenyl-2-butene. Use Newman
Br projections to explain the stereochemical outcome of this reaction.
Dactylyne
A natural product 8.57 Consider the following reaction:
isolated from marine sources
Br
NaOEt
8.52 There are two stereoisomers of 1-tert-butyl-4-chloro-cyclo- EtOH
hexane. One of these isomers reacts with sodium ethoxide in an E2
reaction that is 500 times faster than the reaction of the other isomer.
(a) How would the rate be affected if the concentration of tert-butyl
Identify the isomer that reacts faster and explain the difference in rate
bromide is doubled?
for these two isomers.
(b) How would the rate be affected if the concentration of sodium eth-
8.53 Arrange the following alkenes in order of increasing stability: oxide is doubled?

8.58 Consider the following reaction:

Br
EtOH
 Practice Problems 399

(a) How would the rate be affected if the concentration of tert-butyl
bromide is doubled?
(b) How would the rate be affected if the concentration of ethanol is
doubled?
8.59 When (R)-3-bromo-2,3-dimethylpentane is treated with sodium
hydroxide, four different alkenes are formed. Draw all four products
and rank them in terms of stability. Which product do you expect to be
the major product?
(a) An alkyl halide that produces four different alkenes when treated
with a strong base
(b) An alkyl halide that produces three different alkenes when treated
with a strong base
(c) An alkyl halide that produces two different alkenes when treated
with a strong base
(d) An alkyl halide that produces only one alkene when treated with a
strong base

8.60 When 3-bromo-2,4-dimethylpentane is treated with sodium 8.66 How many different alkenes will be produced when each of the
hydroxide, only one alkene is formed. Draw the product and explain following substrates is treated with a strong base?
why this reaction has only one regiochemical outcome. (a) 1-Chloropentane

8.61 Predict the major product for each of the following E2 reactions: (b) 2-Chloropentane
(c) 3-Chloropentane

(a) Br
NaOH
? (d) 2-Chloro-2-methylpentane
(e) 3-Chloro-3-methylhexane

8.67 In each of the following cases draw the structure of an alkyl halide

(b) Br
NaOH
? that will undergo an E2 elimination to yield only the indicated alkene:

KOC(CH3)3
? (a)
? E2

(c) Br

? E2

(d) Br
KOC(CH3)3
? (b)

8.62 Draw the most stable E1 product that can be produced in each
of the following reactions: (c)
? E2

(a) Br
H2O
Heat ? (d)
? E2

8.68 Consider the following reaction:

(b) OH
conc. H2SO4
Heat ? conc. H2SO4
Heat
OH

8.63 Predict the stereochemical outcome for each of the following E2

reactions. In each case, draw only the major product of the reaction. (a) Draw a mechanism for this reaction.
(b) What is the rate equation of this reaction?

(a) Br
NaOH
? (c) Draw an energy diagram for the reaction.

8.69 Draw the carbocation intermediate that would be formed if each

of the following substrates participated in a stepwise elimination pro-

?
cess (E1). In each case, identify the intermediate carbocation as being
NaOH
primary, secondary, or tertiary. One of the substrates does not undergo
(b) Cl an E1 reaction. Identify which one and explain why.

8.64 Identify the sole product of the following reaction:

Br Cl Br I Cl
(a) (b) (c) (d)
NaOEt
C10H20
8.70 Draw the transition state for the reaction between tert-butyl
chloride and sodium hydroxide.
8.65 For each of the following descriptions draw the structure of
a compound that fits the description. (Note: There are many correct 8.71 The following three reactions are similar, differing only in the
answers for each of these problems.) configuration of the substrate. One of these reactions is very fast, one
400 CHAPTER 8 Alkenes: Structure and Preparation via Elimination Reactions

is very slow, and the other does not occur at all. Identify each reaction Br Br
and explain your choice.
Br
(c) (d)
NaOH

8.75 Explain why the following reaction yields the Hofmann product
exclusively (no Zaitsev product at all) even though the base is not steri-
Br cally hindered:

NaOH Br

NaOEt
EtOH
Br

NaOH
8.76 Propose a mechanism for each of the following transformations:

OH
8.72 1-Bromobicyclo[2.2.2]octane does not undergo an E2 reaction conc. H2SO4
Heat
when treated with a strong base. Explain why not. (a)

8.73 For each pair of the following compounds identify which com-
pound would react more rapidly in an E2 reaction: conc. H2SO4
Heat
Cl
(b) OH
Cl Br Br
(a) (b)

conc. H2SO4
8.74 Indicate whether you would use sodium ethoxide or potassium Heat
tert-butoxide to achieve each of the following transformations: (c) OH

I
EtOH
(a) Br (d) Heat

I
NaOEt
(b) Br (e) EtOH

INTEGRATED PROBLEMS
8.77 Substitution vs. Elimination: Identify the major and minor Br
product(s) for each of the following reactions:
Cl

?
NaOEt
?
?
EtOH
t-BuOK (i)
(a) (b) NaOH
OTs

?
Br
OH

?
KOC(CH3)3

?
conc. H2SO4
NaCl
(j)
Heat
(d) DMSO
(c) OTs

? ?
Br Cl
NaOMe NaOH

? ?
Br Br
NaOEt NaOEt (k) (l)
(e) (f )

Br 8.78 When 2-bromo-2-methylhexane is treated with sodium ethoxide

?
in ethanol, the major product is 2-methyl-2-hexene.
NaOEt
EtOH (a) Draw a mechanism for this reaction.
(g) (b) What is the rate equation of this reaction?
Br (c) What would happen to the rate if the concentration of base is
doubled?

(h)
NaOEt
EtOH ? (d) Draw an energy diagram for this reaction.
(e) Draw the transition state of this reaction.
 Integrated Problems 401

8.79 Predict the major product for each of the following reactions: (a) This reaction is stereoselective, and the major product is trans-
stilbene. Explain why the trans isomer is the predominant product.

? ?
Cl
NaSH DBN To do so, draw the Newman projections that lead to formation of
(b) OTs
(a) each product and compare their stability.

I Br (b) When (R)-1-bromo-1,2-diphenylethane is used as the starting

substrate, the stereochemical outcome does not change. That is,

(c)
NaOH
H2O ? (d)
H2O
Heat ? trans-stilbene is still the major product. Explain.

8.83 Propose a mechanism for the following transformation:

@ !

?
O K
OTs OH

(e) conc. H2SO4

Heat
I
@ !

?
O K
8.84 Propose a mechanism of formation for each of the following
(f ) products:

OTs OEt

EtOH

?
+ +
NaOH Heat
H2O
(g) OTs OEt

OTs
8.85 There are many stereoisomers of 1,2,3,4,5,6-hexachlorocyclo-

(h)
NaOH
H2O ? hexane. One of those stereoisomers undergoes E2 elimination thou-
sands of times more slowly than the other stereoisomers. Identify which
stereoisomer and explain why it is so slow toward E2.
Br

(i)
NaOMe
MeOH ? 8.86 Predict which of the following substrates will undergo an E1
reaction more quickly. Explain your choice.

Br @ ! Br Br

?
O K
or
(j)

8.87 Pladienolide B is a macrocyclic (large-ring) natural product iso-

8.80 Draw all constitutional isomers of C4H9Br and then arrange them
in order of increasing reactivity toward an E2 reaction.
8.81 Propose a mechanism that explains formation of the following
product:
lated from an engineered strain of the bacterium Streptomyces platen-
sis. An enantioselective, 31-step synthesis of it was reported in 2012—
an improvement over a previously reported 59-step approach (Org.
Lett. 2012, 14, 4730–4733):
O

O
conc. H2SO4 OH
Heat

OH OH O
O

8.82 (S)-1-Bromo-1,2-diphenylethane reacts with a strong base to O OH

produce cis-stilbene and trans-stilbene:

(a) Identify the trisubstituted p bond and determine whether it has the
Br
E or Z configuration.
NaOEt (b) How many total stereoisomers are possible for pladienolide B?
(c) Draw the enantiomer of pladienolide B.
(d) Draw the diastereomer that is identical to pladienolide B except for
the configuration of each of the chirality centers directly connected
+ to an ester oxygen.
(e) Draw the diastereomer that is identical to pladienolide B except
for the configuration of the disubstituted p bond that is outside of
trans-Stilbene cis-Stilbene
(major product) the ring.
402 CHAPTER 8 Alkenes: Structure and Preparation via Elimination Reactions

CHALLENGE PROBLEMS
8.88 Steroids (covered in Chapter 26) and their derivatives are among
the most widely used therapeutic agents. They are used in birth con-
trol, hormone replacement therapy, and the treatment of inflammatory
conditions and cancer. New stereoid derivatives are discovered regu-
larly by systematically modifying the structure of known steroids and
testing the resulting derivatives for therapeutic properties. As part of a
synthetic strategy for preparing a class of promising steroid derivatives,
compound 1a was treated with TsCl and pyridine followed by sodium
acetate (CH3CO2Na) to give compound 2a (Tetrahedron Lett. 2010,
51, 6948–6950).
(a) Explain why the mechanism shown is inconsistent with this
observation.
(b) Classify this reaction as stereoselective or stereospecific and
explain your choice.
8.91 The following sequence of reactions was performed during a
synthesis of (+)-coronafacic acid, a key component in the plant toxin
coronatine (J. Org. Chem. 2009, 74, 2433–2437). Predict the product
of this reaction sequence and justify the regiochemical outcome of the
second reaction.

R′ CH3
CH3
R O
H O
O

?
OH
O 1) TsCl, pyridine
O O 1
2) DBU
O 1a : R = R′ = H OH
1b : R = H; R′ = D CO2CH3
O 1c : R = D; R′ = H

8.92 We have seen that an E2 reaction generally proceeds from a

(a) Sodium acetate functions as a base in this instance. Draw the
conformation in which the b proton is anti-periplanar to the leaving
structure of 2a.
group. A similar geometric requirement is also observed for other
(b) Deuterium (D) is an isotope of hydrogen, and deuterons will typi- types of reactions such as the one below (J. Am. Chem. Soc. 2010,
cally behave very much like protons (although small differences in 132, 2530–2531). Under acidic conditions, compound 1 rearranges to
reaction rates are typically observed). If 1b or 1c were treated with form mechanistic intermediate 2, which then undergoes three addi-
TsCl and pyridine, followed by sodium acetate, 2b or 2c would tional mechanistic steps (along with the loss of an N2 leaving group)
be produced, respectively. Identify which product (2b or 2c) is to give product 3. The conversion of 1 S 2 is beyond the scope of
expected to contain deuterium and justify your choice. our current discussion. Draw a mechanism for the final three steps, as
described: (x) The alkyl group anti-periplanar to the N2+ group under-
8.89 Compounds 1 and 2 exhibit an oxetane ring (a four-membered goes a 1,2-shift to allow a backside displacement of N2. (y) The alco-
ring containing an oxygen atom), which is a very important structural hol oxygen attacks the resulting carbocation. (z) The resulting oxo-
feature in a number of natural products. For example, an oxetane ring nium ion is deprotonated.
is present in the structure of taxol, used in the treatment of breast can-
cer. When either 1 or 2 is treated with TsCl and pyridine, followed by HO
O O Several
t-BuOK, the Zaitsev elimination product dominates, despite the use of R mechanistic
a sterically hindered base (Tetrahedron Lett. 2007, 48, 8353–8355). steps R O
x y z
Determine the stereochemical outcome for each of these processes R 3
and draw the expected product in each case. Use Newman projections N N N
!
to justify your answers. R
1 N3 2

OH OH
8.93 When 2-iodobutane is treated with a variety of oxyanion bases
Ph Ph in DMSO at 50 °C, the percentage of 1-butene formed among total
1 O 2 O butenes is found to be dependent on the choice of base, as seen in the
chart below (J. Am. Chem. Soc. 1973, 95, 3405–3407):
8.90 Compound 1 is observed to undergo debromination upon % 1-BUTENE
treatment with DMF to afford an alkene. The E isomer (compound 2) NAME OF BASE STRUCTURE OF BASE (IN TOTAL BUTENES)
is obtained exclusively (none of the Z isomer is observed). A concerted
Potassium O
mechanism (shown below) has been refuted by the observation that
benzoate 7.2
diastereomers of 1 also afford the E isomer exclusively when treated
OK
with DMF (J. Org. Chem. 1991, 56, 2582–2584):
Potassium
phenoxide OK 11.4
O
Br H
H N Sodium 2,2,2-
NaOCH2CF3 14.3
trifluoroethoxide
H Br (DMF)
1 2 Sodium ethoxide NaOEt 17.1
 Challenge Problems 403

(a) Identify the trend observed by comparing the basicity of the oxy- 8.95 When the given 2-butyl compounds are treated with t-BuOK in
anion bases and then describe the correlation between reactivity t-BuOH at 50 °C, the major product is generally 1-butene (as expected
(base strength) and selectivity (specifically regioselectivity). with a sterically hindered base), while the minor products are cis-2-
(b) The pKa of 4-nitrophenol is 7.1. Based on the trend in the previous butene and trans-2-butene. In cases where the leaving group is a halo-
part of this problem, provide an estimate for the percentage of gen (I, Br, or Cl), the trans alkene is favored over the cis alkene. However,
1-butene that is expected if 2-iodobutane is treated with the conju- the cis isomer becomes the favored 2-alkene when the leaving group is
gate base of 4-nitrophenol in DMSO at 50 °C. a tosylate group (J. Am. Chem. Soc. 1965, 87, 5517–5518). Provide a
transition state argument, including relevant Newman projections, that
8.94 During a recent total synthesis of (+)-aureol, a potential anti- explains this difference.
cancer agent isolated from a marine sponge, the following Lewis
Y
acid catalyzed rearrangement was employed (Org. Lett. 2012, 14, t-BuOK
4710–4713). Provide a plausible mechanism for this biosynthetically t-BuOH +
inspired process (Hint: review Section 3.9) and make sure to include a
rationale for the observed stereochemistry of the product.
Y trans:cis
OAc I 2.2
OAc
Br 1.4
Cl 1.3
OH
OTs 0.6
BF3