FIVE-MEMBERED RING FORMATION 138 5 Membered Rings 1

12 Pages·1998·0.1 MB·English

FIVE-MEMBERED RING FORMATION 138
5 Membered Rings
HO O
CO H CO H
2 2
HO OH HO OH
PGF2a PGE2
Me H Me
Me
Me
Me
Me Me
Me
Hirsutene Modhephane Isocumene
1. Intramolecular S 2 Reactions
N
2. Intramolecular Aldol Condensation and Michael Addition
3. Intramolecular Wittig Olefination
4. Ring Expansion and Contraction Reactions
a. 3 fi 5
b. 4 fi 5
c. 6 fi 5
5. 1,3-Dipolar additions
6. Nazarov Cyclization
7. Arene-Olefin Photocyclization
8. Radical Cyclizations
9. Others
Synthesis 1973, 397; ACIEE 1982, 21 , 480;
Intramolecular S 2 Reaction 5-exo-tet: favored
N
O
LDA JCSCC 1973, 233
O
Br
O
O O
CO Me
2 CO Me
2
Br
CN CN OH
JACS 1974, 96 , 5268
O
FIVE-MEMBERED RING FORMATION 139
O Cl
O JACS 1979,
101 , 5081
RO2C CO R Cl RO2C CO2R
2
O O
NaH, DMSO
JCSCC 1979, 817
TsO
Intramolecular Aldol Condensation 5-exo-trig: favored
intramolecular aldol condensation of 1,4-diketones
O O
R
R
O
R'
R'
O O
CH
3
CH3 TL 1982,
29, 2237
O
CH
3
CH
3
Br Br
O
NaOMe, MeOH
O JACS 1980,
102 , 4262
O CO2Me
CO Me
2
O O
NaOH JOC 1983,
O O 48 , 1217
O
Intramolecular Michael Addition 5-exo-tet: favored
Organic Reactions 1995, 47, 315-552
O
O JACS 1979,
101 , 7107
MeO C O O
2
FIVE-MEMBERED RING FORMATION 140
Intramolecular Wittig Olefination Tetrahedron 1980, 36, 1717
O O
O 1) (MeO) P(O)CH - P(OMe)
2 2 2
O
2) Collins O
C H
5 11
THPO
C H
OTHP 5 11
THPO
OTHP JOC 1981, 46 , 1954
O CO2H
base
C H
5 11
THPO
OTHP C H
5 11
HO
OH
Ring Expansion Reactions
- 3 fi 5: Vinyl Cyclopropane Rearrangement Organic Reactions 1985, 33, 247.
O _
OTMS
SPh2 O
O
H O O
H H
O
O O
TMSO
JACS 1979, 101 , 1328
O
H
O
- 4 fi 5: Reaction of cyclobutanones with Diazomethane
Cl Me Cl Me
CHN
2 2
Me
O
O
O TL 1980,
Me Cl Me Me 21 , 3059
CHN O
2 2
Cl
Cl
Cl
Cl O
O
Cl
Cl
CH Cl
3 CH N
2 2 CH
O CH 3
3
O CH
3
Ph JACS 1987,109 , 4752
Ph
FIVE-MEMBERED RING FORMATION 141
Ring Contraction Reactions
- 6 fi 5: Favorskii Reaction Organic Reactions 1960, 11 , 261
O O _ OH -O OH
CO H
Cl _ 2
1,3-Dipolar Addition to Olefins 1,3-Dipolar Cycloaddition Chemistry , vol 1 & 2 (A.
Padwa ed.) (Wiley, NY 1984); ACIEE 1977, 16 , 10. Chem Rev. 1998, 98, 863.
1,3-Dipole (4p )
LUMO
+
_
b
a c
4p s + 2p s Alkene (2p )
HOMO
- trimethylenemethane (TMM) ACIEE 1986, 25 , 1. Synlett 1992, 107.
high
•
temperature
•
TMM
CO Me
2 MeO2C MeO2C CO2Me
H CH
D , MeCN • • 3
N -N •
N 2
H
•
JACS 1981,
103 , 2744
note: TMM usually reacts poorly w/ electron defficient olefins
_
Pd(0)
Me3Si OAc +
PdLn
O O
O Me3Si OAc H O
TL 1986, 27 , 4137
Pd(0), 80°C
MeO2C CO2Me
Ni(COD) , 35 °C
2 ACIEE 1985, 24 , 316
TL 1983, 24 , 5847
CO2Me CO2Me
- a ,a '-dihaloketones
O
O OFeLn
Fe(CO)9 Ar ACR 1979, 12 , 61
+
Br Br Ar
FIVE-MEMBERED RING FORMATION 142
- nitrones ACR 1979, 12 , 396; Organic Reactions, 1988, 36 , 1
O - O
R+N R2 R1 N
1
R R2 R3
3
Nitrone
JACS 1964,
O 86 , 3756
- O N
N
Me N O OH
O MeNHOH, Me 12)) MHe,I Pd/C Me2N Me JOC 1984,
EtONa 2
49 , 5021
H H H H H
MeO2C NH Bn MeO2C NH Bn
N
N
O - O JACS 1983,
S S 104 , 6460
C H
4 9 C H
4 9
- nitrile oxides
O N O +N O- N O O OH
H
ArNCO 2 JACS 1992,
104 , 4023
CO2Et CO2Et CO2Et CO2Et
O O OH O O 1) DHP, PPTS OTHP 1) Swern
Bu2BOTf, iPr2EtN, CH2Cl2, ›fl 2) NH2OH•HCl
N O CH2Cl2, -78°C N O 2) LAH AcONa, MeOH
O CH3 (60%) OH (89%)
H
Ph Ph
(99%)
OTHP OTHP
OTHP
NCHaO2CCll2, H2O, THPO N+ O_ HM2e, ORHan, eBy( ONMi, eH)32O,
N (88%) N (88%) O
OH O OH
OTHP 1) PPTS, EtOH, ›fl O O
1) TBS-Cl, DMF, HF•pyridine,
2) (CH)C(OMe) ,
imidazole OH PPT3S2 2 CH3CN, pyridine Cassiol
2) nBuLi, THF
TL 1996, 37, 9292
3) Swern (73%)
BuSn
3 O (48%)
O TBSO O TBSO O HO OH
(80%)
O O OH
FIVE-MEMBERED RING FORMATION 143
OTBS OTBS OTBS
LAH
TL 1993, 34, 3017
ON_ + O N OH NH2
Arene -Olefin Photocyclization Organic Photochemistry 1989, 10 , 357
- the photochemistry of benzene is dominated by the singlet state
1 *
hn
*
hn * OAc
OAc
*
JACS 1982,
O Me2CuLi O 104 , 5805
JCSCC, 1986 247
Me
1) FVP
*
2) H , Pd/C
2
*
hn
isocume
+ +
*
Tetrahedron
1981,37 , 4445
*
hn * *
OMe
OMe
JACS 1981,
103 , 688
OMe
cedrane
* HO
AcO hn AcO * H+
H
TL 1982, 23 , 3983
TL 1983, 24 , 5325
FIVE-MEMBERED RING FORMATION 144
Intramolecular Photochemical [2+2]
"Rule of Five"
O O
hn
O O
O O JOC 1975, 40 , 2702
JOC 1979, 44 , 1380
hn
O
O
Nazarov Cyclization review: Synthesis 1983, 429 Organic Reaction 1994, 45, 1
- cyclization of allyl vinyl or divinyl ketones
O O
H PO /HCO H
3 4 2
O
O
H PO /HCO H
3 4 2
- 1,4-hydroxy-acetylenes
H SO , MeOH JOC 1989,
HO 2 4
OH H H 54 , 3449
O
OH OH
- Silicon-Directed Nazarov
O O
Tetreahedron
FeCl
3 1986, 42 , 2821
SiMe
3
Me Me
- Tin -directed Nazarov TL 1986, 27 , 5947
Radical Cyclization
B. Giese Radicals in Organic Synthesis: Formation of Carbon-Carbon Bonds
(Pergamon Press; NY) 1986; Bull. Soc. Chim. Fr. 1990, 127 , 675; Tetrahedron 1981, 37 ,
3073; Tetrahedron 1987, 43, 3541; Advances in Free Radical Chemistry 1990, 1, 121.
Organic Reactions 1996, 48, 301-856.
Radical Addition to multiple bonds:
1. Free radical addition is a two stage process involving an addition step followed by an
atom transfer step.
2. In general, the preferred regioselectivity of the addition is in a manor to give the
most stable radical (thermodynamic control)
FIVE-MEMBERED RING FORMATION 145
Advantages of free radical reactions:
1. non-polar, little or no solvent effect
2. highly reactive- good for hindered or strained sysntems
3. insensitive to acidic protons in the substrates (i.e. hydroxyl groups do not
necessarily need to be protected
Mechanism of radical chain reactions
1. initiation
2. propagation
3. termination (bad)
Formation of carbon centered radicals:
tin hydride reduction of
alkyl, vinyl and aryl halides,
alcohol derivatives:
xanthates, thionocarbonate, thiocarbonylimidazolides
organosselenium & boron compounds
carboxylic acid derivatives (Barton esters)
reduction of organomercurials
thermolysis of organolead compounds
thermolysis or photolysis of azoalkanes.
Radical Ring Closure
For irreversible ring closure reaction, the kinetic product will predominate.
Both the 5-exo-trig and 6-endo trip are favored reactions, with the 6 exo-trig mode
producing the most stable radical. However, the 5-exo-trig is about 50 time faster
• •
k1,5 • k1,6
kinetically thermodynamically
favored favored
•
• + • 3-exo-trig
vs
100 : 0 4-endo-trig
• •
• + 4-exo-trig
vs
100 : 0 5-endo-trig
•
•
• + 5-exo-trig
vs
6-endo-trig
98:2
•
• •
+ 6-exo-trig
vs
85:15
7-endo-trig
•
• •
7-exo-trig
+ vs
8-endo-trig
100 : 0
FIVE-MEMBERED RING FORMATION 146
•
•
and
radicals open up fast and are not synthetically useful;
often used as probes for radical reaction
Effects of substituent on the regiochemistry of the 5-hexenyl radical cyclization
•
•
•
+
48:1
•
•
•
+
>200:1
•
•
•
+
2:3
•
•
•
+
< 1:100
Stereochemistry of 5-hexenyl radical cyclization
1-, or 3-substitued 5-hexenyl radicals give cis disubstituted cyclopentanes
2-, or 4-substituted 5-hexenyl radicals give trans disubstitued cyclopentanes
2 Bu SnH H
Br 3 R R
•
+
R H R
65 : 35
prefered transition state
R
• R R R
3 Br H +
H
75 : 25
H
4
Br • R +
R H
R 83 : 17 R
R
Bu SnH
3 R
+
Br •
1 H
R 73 : 27 R
FIVE-MEMBERED RING FORMATION 147
Br
nBuSnH, JACS 1983,
AIBN 105 , 3720
OH
CN OH CN
Bu SnH,
3
AIBN JACS 1990,
112, 5601
CO Me
2
Br CO Me
2
Br OH
Si H Si H
O Bu3SnH O H2O2 OH
THPO THPO
THPO
multiple cyclizations: D. Curran Advances in Free Radical Chemistry 1990, 1, 121.
OTBS
O OAc
1) NaBH4, CeCl3 1) LDA, THF O
2) Ac2O, Et3N 2) TBSCl 70 °C O
OTBS
PhSe
PhSeCl, CH2Cl2 O H2O2 O THPO CuSMe2 Li+
O O
THPO
1) PPTS, EtOH I 1) Me Si Li
2) LAH 3
(1.0 equiv)
CO H
2 3) (CF SO ) O I
3 22
pyridine
2) CsF
4) Bu NI, PhH
4
Me
I • H
Bu SnH, AIBN
3 JACS 1985,
PhH, reflux
107 , 1148
H H
(±)-hirsutene
O CCHuB3Mr•SgMBre, HO O 12)) ID2BU O O
O 2 O O MgBr
CuBr•SMe , THF
2
O 1) LAH
O HO O 23)) CNHaI3SO2Cl CO2Me 1) (CeHxc3eMssg)Br Br
4) Li 2) Me SiBr
5) CrO , H SO , H O 3
3 2 4 2
H H
Bu3SnH, AIBN • (±)-capnellene
PhH, reflux
Tetrahedron Lett.
1985, 41, 3943
H C H
3