Chapter 13

CHAPTER 13
1. Photolysis cleaves BrCCl3 to give a trichloromethyl radical that adds to one of the alkene moieties to generate a
secondary radical. This radical then adds internally via a 5-exo-trig process to give the furan and a primary radical.
Subsequent reaction with BrCCl3 gives the bromide as the final product and regenerates the chain carrier, CCl3.
Note the single-headed arrows denoting one-electron transfers.
O

CCl3

CCl3

BrCCl3
CCl3

Br

CCl3

2. Mercury removes the chlorine to generate a radical. This radical product is benzylic with respect to one fluorene
moiety and allylic to the alkene moiety. This alkene provides a resonance pathway to the other fluorene pathway
and to the other phenyl ring. This extensive delocalization leads to the great stability of this radical.

Hg

Cl

J. Am. Chem. Soc., 1957, 79, 4439.

3. Fremy's salt is stable because the radical can be delocalized in a way that involves both of the SO3 moieties.
One resonance contributor is shown as an example, but delocalization occurs on all seven oxygen atoms in the
molecule. Obviously, the negative change of each anion (O) is delocalized on the SO3 moieties.
O
O N O
S
S O
O
O O

O
S
O
O

O
N

O
S O
O

see Chem. Ind., 1953, 244

4. In both products, the methyl group on the six-membered ring has the same configuration relative to the ring
juncture hydrogen atoms. The variation occurs in the carbomethoxy group on the five-membered ring. The radical
cyclization step to form the six-membered ring proceeds by the favored conformation having the methyl group and
the dienyl unit equatorially disposed, rather than the higher energy transition state having an axial methyl.
Cyclization via the bis-equatorial transition state leads to the relative stereochemistry shown.

Organic Synthesis Solutions Manual

I
Me
Ts

Ph

Bu3 SnHAIBN
PhH , reflux

Me
Ts N

Ph
CO 2Me

Ts

CO 2Me

Ts N

Ph

CO2 Me

Me

see J. Org. Chem., 2002, 67, 6001

Me

CO2 Me

H CO2 Me

Me

Ph

H
20%

Ph

Ts

DISFAVORED

39%

5. Formation of the cyclopropane rings in these cases involves CH insertion of the carbene. In the case of the
cyclopentane derivative, two envelope conformations (A and B) are shown. Only the CH on the same side as the
carbene moiety is close enough for the insertion reaction. The reaction therefore generates only the cis derivative.
The seven-membered ring derivative is shown in two chair conformations (C and D), although the boat
conformations are close in energy to C and D (see Sec. 1.5.B). In C, the carbene can only insert into the axial C
H but in D it can insert only into the equatorial CH. The result is that both conformations lead to product, a
mixture of cis and trans- isomers.
CH:
H
H
H
A

H
H

H
B

H
CH:

H
C
see Angew. Chem. Int. Ed. Engl., 1968, 7, 891

CH:

CH:

H
D

6. These results are explained by analyzing the intermediate that results when RS adds to the alkene, namely, RSCH2-C(R)H. If the R group can stabilize this radical, the initial addition will be faster, making the overall reaction
greater. Since the phenyl group can delocalize the radical by resonance, which shows the largest rate relative to the
simple alkyl substituent. Both the RO and MeO2 C groups can stabilize an adjacent radical by inductive effects,
with the RO group being better able to accommodate the lone electron. The ClCH2 group is unable to stabilize the
adjacent radical since an intervening carbon separates the Cl and C. The rate for this last substituent is, therefore,
lower than that of the simple alkyl group.
see J. Am. Chem. Soc., 1959, 81, 1144.
7. Benzophenone is a sensitizer (see Sec. 13.4 and Sec. 11.10.B). The aldehyde does not absorb the radiation to
form a radical very efficiently. Benzophenone absorbs the energy to form a singlet radical, which is transformed to
the triplet. Intersystem crossing of the triplet benzophenone to pentanal leads to triplet pentanal, and the energy
required for conversion to the reactive singlet aldehyde is much lower. This is outlined below. The result is that
the aldehyde radical, once formed by use of the sensitizer, adds to the conjugated ester to give the coupled product.

Chapter 13

h

Ph

Ph

O
Ph

O
Ph

O
R

Ph

Ph

3
H

O
Ph

Ph

CO2 Me

O
R

CO2 Me

For related information, see Can. J. Chem., 1977, 55, 3986.

8. The radical initiator (AIBN) removes a H from Bu3SnH to give Bu3Sn, which reacts with the aryl halide to
give the aryl radical. The radical carbon is positioned to remove the H from the amide N-methyl group to give the
N-stabilized radical shown. Conjugated addition to the C=C unit leads to the spirocycle, and the resultant radical
reacts with additional Bu3SnH to give the final product and regenerate the radical carrier.

Br
H3 C
N

Bu3 Sn

O
N
Me

H2 C

H 3C

CN

N
Me

CN

N
Me

N
Me
O
Bu3 SnH

CN

CN
see Org. Lett., 2000, 2, 2639

N
Me

CN

9. The peroxide induces cleavage of carbon tetrachloride to give CCl3, which adds to the alkene moiety to
generate radical A. Radical A is a cyclobutylcarbinyl radical, which rapidly opens to a butenyl radical (B).
Reaction of B with carbon tetrachloride gives the final product, and regenerates the chain-carrying CCl3 radical.
The cyclobutylcarbinyl-butenyl radical equilibrium is analogous to the well-known cyclopropyl-carbinyl-propenyl
radical equilibrium.

CCl3

Cl
ClCCl3

CCl3
A

CCl3
B

CCl3

see J. Am. Chem. Soc.,

1950, 72, 2407; and
Bull. Soc. Chim. Fr.,
1950, 1056.

Organic Synthesis Solutions Manual

10. This is a tandem radical-cyclization sequence. Initial reaction of the seleno ester with AIBN generates an acyl
radical, which cyclizes to the first C=C unit to form a cyclohexanone ring containing the radical chain carrier. A
second cyclization sets the tricyclic structure, and hydrogen transfer from Bu3SnH gives the final product. The
stereochemistry of the ring junctures is set by the chair-like transition states for the first cyclization. and the relative
conformations of the two six-membered rings for the second ring-closing reaction.

AIBN

PhSe
H

Bu3 SnH

H
H

O
see J. Chem. Soc., Perkin Trans. 1, 1996, 45 , 31

11. According to the cited reference, this reaction proceeds by photochemical extrusion of nitrogen to form the
carbene. A Wolff rearrangement leads to the ketene shown, and a [2+2]cycloaddition (Sec. 11.10.C) leads to the
cyclobutanone. On prolonged exposure to light, the cyclobutanone, re-drawn for perspective, extrudes ketene to
give the cyclopentene product.

O
C

O
h
, 10C
N2
CO2 Et

- N2

CO2 Et
Wolff rearrangement

EtO2 C

CH2 =C=O EtO2 C

[2+2]

CO2 Et
see J. Org. Chem.,
1999, 64, 4079

CO2 Et

12. Reaction of the MeS moiety with AIBN generates a tertiary radical. The radical can add to the alkene across
the ring by either path a (to give A) or path b (to give B). Both are reasonable and energetically accessible.
However, A was formed in 20% and B in 65% in the cited reference. Therefore,, it is clear that path b is favored to
give the major product, B.

Chapter 13

Me

O
Me

SPh

O
a

O
Me
O

O
Me

see J. Am. Chem. Soc., 1987, 109, 2504

A

H
O Me

O
B Me

13. Initial carbene addition to one C=C unit of the diene leads to the bicyclic diketone. Treatment with LDA and
trapping both enolate anions as the OTBS enol ether allows a Cope rearrangement (Sec. 11.12.C), which leads to
the bridged bicycle. Hydrolysis of the OTBS unit gives the targeted diketone.

LDA , TBSCl
THF

Rh2 (OOct)4 , CH2 Cl2

N2

TBSO

see J. Org. Chem., 2000,

65, 4261

OTBS

TBAF , THF
TBSO

OTBS

OTBS

14. The three products are A, B, and C. Addition of the carbene to the central aromatic ring to give products A and
C disrupted the aromatic nature of the system, although two "intact" rings remain. Product B results from addition
and ring expansion. The cyclopropanation product C predominates (80%) since it is less sterically hindered in the
transition state.

see Annalen, 1966, 692, 58

A

15. The initial reaction is a ring-opening metathesis reaction to give the diene. The two C=C units are positioned
to undergo a Cope rearrangement (Sec. 11.12.C), opening the four-membered ring and forming the eight-membered
ring in the final product.

Organic Synthesis Solutions Manual

H H
Me

Me

N Mes
Mes N
Cl
5% Cl Ru Ph
PCy3

H
Me

CH2 =CH2

H H
Me

Me

H
Me

Me

Me

Me
O

H
O

see J. Am. Chem. Soc., 2000, 122, 8071

16.
O

(a)

(b)

n-C 3 H
7n-C H
3 7

(c)

Cl

see J. Org. Chem.,

1986, 51, 5043

see Aust. J. Chem., 1992, 45, 925

see J. Org. Chem.,

1999, 64, 3650

OH
OH

(d)

(e)

OPMB
OTBS

(f)

N COCF3
N

see J. Am. Chem. Soc.,

1995, 117, 7283

SPh

Angew. Chem. Int. Ed.,

2002, 41, 4573

J. Org. Chem., 2003, 68, 7983

O
O

(g)

(h)

(i)

C3 H7

OBn
EtO
OBn
J. Am. Chem. Soc., 2003,
125, 10772

CO2 Me

see Chem. Lett., 1995, 953

J. Am. Chem. Soc., 2002, 124, 14655

H
O

(k)

(j)
2

Ph

(l)

O
Ph

Ph
Tetrahedron, 2002,
58, 6179

see J. Org. Chem., 2000, 65, 1780

CO 2Et

(m)

HO HO
N

(n)

OTBDPS
J. Am. Chem. Soc., 2002, 124, 13121

Ph
J. Org. Chem., 2002, 67, 3788

Me n-C8 H17

O
A

MeO Me

(o) Br
Br

OAc

AcO
Me

Me see J. Chem. Soc., C

1969, 336

see J. Org. Chem.,

2000, 65, 4241

Chapter 13

OBn

(p)

OH

(q)

(r)

EtO2 C
J. Am. Chem. Soc.,
2002, 124, 384

OBn

(t)

(s)

(u)

OH

CO2 Me

CO2 Me

Me
see J. Org. Chem.,
1978, 43, 2282

Tetrahedron, 2002,
58, 5225

MeO 2C

OH

O
J. Org. Chem., 2003, 68, 7219

see Synthesis , 1996, 71

see J. Org. Chem.,2000, 65, 5066

MeO

OH

(v)

(w)

Me (+ anti)
see Tetrahedron Lett.,
1984, 25, 3927

HO

(x)
Me

Me

see Chem. Pharm. Bull.,

1969, 17, 814; and
OMe J. Org. Chem., 1968,
33, 690

OBn OH
see J. Am. Chem. Soc.,
1983, 105, 4833

OBn
O

(y)
H
Br

O
O

Me

Ph

(z)

NH2

MOMO
J. Am. Chem. Soc., 2003, 125, 2400

Ph
see J. Org. Chem., 1999, 64, 9450

J. Am. Chem. Soc., 2003,

125, 8112

(aa) MeO

CO2 Me

O
OTBDPS
Et
O

O
N

HO

H O H

O
(ab) Org. Lett. 2002, 4, 4301

(ac)

N COCF 3
O

Tetrahedron, 2002,
58, 2175

Tetrahedron, 2004,
60, 4901

MeO

(ad)

OBn

17. All of the following problems were taken from published syntheses. The sequences and reagents can be looked
up. If you devise your own synthesis and then check the literature, you can compare your route to that published.
More importantly, you may find that some of the steps you used were tried in the literature and discussed. You

Organic Synthesis Solutions Manual

may also devise a novel and useful alternative synthesis. In all cases, your syntheses should be critiqued by and
discussed with your instructor.
(a) See Tetrahedron Lett., 1996, 37, 5929.
(b) See J. Am. Chem. Soc., 2002, 124, 8584.
(c) See Tetrahedron Lett., 2000, 41, 3801.
(d) See J. Am. Chem. Soc., 2002, 124, 13342.
(e) See J. Org. Chem., 2002, 667, 7750.
(f) See J. Org. Chem., 1998, 63, 1379.
(g) See J. Org. Chem., 1998, 63, 2699
(h) See J. Am. Chem. Soc., 1999, 121, 5653.
(i) See Synthesis, 2000, 557.
(j) See J. Am. Chem. Soc., 2002, 124, 2080.
(k) See J. Org. Chem., 2000, 65, 7231.