Chapter 13 1 CHAPTER 13 - textbooks.elsevier.com

Chapter 13 1

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

O

CCl3

O

CCl3

BrCCl3O

CCl3Br

•

•

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.

•Cl

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

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

NS

O

O

OSO

OO

• O

NS

O

O

OSO

OO

•

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.

Copyright © 2011 Elsevier Inc. All rights reserved.

2 Organic Synthesis Solutions Manual

NTs

Ph

CO2Me

I

MeBu3SnH–AIBNPhH , reflux

N

H

H

CO2Me

Ph

Ts

Me

N

Me

TsPh

CO2Me

N

H

H

CO2Me

Ph

Ts

Me

NMe

TsPh

CO2Me

20% 39%

DISFAVORED

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

5. Formation of the cyclopropane rings in these cases involves C—H insertion of the carbene. In the case of the

cyclopentane derivative, two envelope conformations (A and B) are shown. Only the C—H 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 C—H. The result is that both conformations lead to product, a

mixture of cis and trans- isomers.

H

CH:

H

CH:

H

CH:H

H

H

HH

CH:H

H

H

H

see Angew. Chem. Int. Ed. Engl., 1968, 7, 891A B C D

6. These results are explained by analyzing the intermediate that results when RS• adds to the alkene, namely, RS-

CH2-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 MeO2C 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 3

O

Ph Ph

O

Ph Ph

O

Ph Ph

O

R HO

R H

O

Ph Ph

O

R HCO2Me

O

RCO2Me

1

3

1

31

h

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.

NCN

O

NH3C

Me

Br

Bu3Sn•

NCN

Me

N

O

NCN

O

NH3C

Me

Bu3SnH

NCN

O

NH2C

Me

H

NCN

Me

N

O

see Org. Lett., 2000, 2, 2639

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

CCl3 CCl3

Cl—CCl3

A B

CCl3

Cl

•

• see J. Am. Chem. Soc., 1950, 72, 2407; and Bull. Soc. Chim. Fr., 1950, 1056.



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.

PhSe

O

O

AIBN

O

Bu3SnH

O

O

H H

H

H

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

N2CO2Et

O

CO2Et

OEtO2C

O

CO2Et

EtO2C

C

O

CO2Et

h , –10°C

see J. Org. Chem., 1999, 64, 4079– CH2=C=O

- N2

Wolff rearrangement

[2+2]

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 5

O

O

Me SPh

O

OMe

O

O

Me

O

O Me

H

A

O

O

Me

O

OMe

H

B

•

• •

ab

a b

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

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.

N2

OO

TBSO OTBS

O O

O OTBS

TBSO OTBS

O O O O

see J. Org. Chem., 2000, 65, 4261

Rh2(OOct)4 , CH2Cl2LDA , TBSCl THF

TBAF , THF

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 B C

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.



Me

OMe

MeHH

H

N N

RuPh

PCy3ClCl

Mes Mes

CH2=CH2

Me

OMe

MeHH

H

O

Me

Me

MeH

H

5%

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

16.

(a)

N

n-C3H7n-C3H7

Cl

see J. Org. Chem.,1986, 51, 5043

(b)

OOO O

see J. Org. Chem., 1999, 64, 3650

(c)

O

O

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

(d)

see J. Am. Chem. Soc., 1995, 117, 7283

OHOH

(e)

O

OTBSOPMB

Angew. Chem. Int. Ed., 2002, 41, 4573

(f)

N

N

SPh

COCF3

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

(g)

OBnOBn

OO

OEtO

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

(h)

see Chem. Lett., 1995, 953

(i)

O

CO2MeO

C3H7

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

(j)

Ph Ph2

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

(k)

H

Tetrahedron, 2002, 58, 6179

(l)

NO

O

Ph

PhO

MeMeO

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

(m)

CO2Et

OTBDPS

O

A

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

(n)

HO

AcOMe Me

Me n-C8H17

NHO

see J. Chem. Soc., C 1969, 336

(o)

OAcBr

Br

see J. Org. Chem., 2000, 65, 4241


Chapter 13 7

(p)

OEtO2C

OBn

OBn

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

(q)

OH

Tetrahedron, 2002, 58, 5225

(r)

O

Mesee J. Org. Chem.,1978, 43, 2282

(s)

N CO2Me

O

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

(t)

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

OH

OH

(u)

MeO2C

CO2Me

see Synthesis , 1996, 71

(v)

OH

Me

see Tetrahedron Lett., 1984, 25, 3927

(+ anti)

(w)

N

OMeO

HO

MeO

Me

see Chem. Pharm. Bull., 1969, 17, 814; andJ. Org. Chem., 1968, 33, 690

(x)

Me

OBn OH

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

(y)

O

O

ON

O

OBn

Br Me

H

J. Am. Chem. Soc., 2003, 125, 8112

(z)

N O

Ph CO2Me

Phsee J. Org. Chem., 1999, 64, 9450

(aa)

MOMO

MeO O

NH2

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

(ab)

N

OTBDPSEt

O

OO

H H

Org. Lett. 2002, 4, 4301 (ac)

O

O

HO

Tetrahedron, 2002, 58, 2175 (ad)

N

O

COCF3

OBn

MeOTetrahedron, 2004, 60, 4901

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



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.


Chapter 13 1 CHAPTER 13 - textbooks.elsevier.com

Documents

Transcript of Chapter 13 1 CHAPTER 13 - textbooks.elsevier.com