C=C BOND FORMATION 103

12 Pages·1998·0.08 MB·English

C=C BOND FORMATION 103
C=C Bond Formation C&S Chapt. 2 # 5,6,8,9,12
1. Aldol Condensation
2. Wittig Reaction (Smith, Ch. 8.8.A)
3. Peterson Olefination
4. Julia-Lythgoe Olefination
5. Carbonyl Coupling Reactions (McMurry Reaction) (Smith Ch. 13.7.F)
6. Tebbe Reagent
7. Shapiro and Related Reaction
8. b- Elimination and Dehydration
9. From Diols and Epoxides
10 From Acetylenes
11. From Other Alkenes-Transition Metal Catalyzed Cross-Coupling and Olefin
Metathesis
Aldol Condensation -Aldol condensation initially give b -hydroxy ketones which under
certain conditions readily eliminated to give a,b -unsaturated carbonyls.
OMe OMe
LDA, THF, -78°C
Tetrahedron
O O
1984, 40, 4741
O O
CHO
OMe OR O -78C fi RT OMe OR O
Robinson Annulation : Sequential Michael addition/aldol condensation between
a ketone enolate and an alkyl vinyl ketone (i.e. MVK) to give a cyclohex-2-en-1-
one
JOC 1984, 49 , 3685 Synthesis 1976, 777.
O O
O
L-proline O
O
Weiland-Mischeler Ketone
(chiral starting material)
Mannich Reaction - a ,b -unsaturated carbonyls (a -methylene carbonyls)
H C=O, Me NH•HCl
O 2 2
O
H C N Me Cl-
2 + Me
Mannich Reaction
C=C BOND FORMATION 104
Wittig Reaction review: Chem. Rev. 1989, 89, 863.
mechanism and stereochemistry: Topic in Stereochemistry 1994, 21, 1
- reaction of phosphonium ylide with aldehydes, ketones and lactols to give
olefins
strong _
Ph3P + base +
R X R PPh R PPh R PPh
3 3 3
X - ylide phosphorane
O
+
R1 R2 Ph3P O - Ph3P O - Ph3P=O R R2
R R1R2 R R1R2 R1
betaine oxaphosphetane
- Olefin Geometry
O
L S
Z- olefin
Ph P
3
L S
O
L S
E- Olefin
Ph P
3
S L
- With "non-stabilized" ylides the Wittig Reaction gives predominantly Z-olefins.
Seebach et al JACS
- O
O
O S L L S
S L S L
L S L S
+PPh3 P+Ph3 +PPh3
O OPPh
3
L S - Ph P=O S S
3
Ph3P L S
L S L L
L S Z-olefins
- "Stabilized ylides" give predominantly E-olefins
O
+ _ L S S
Ph3P CO2Me CO2Me
L
C=C BOND FORMATION 105
- Betaine formation is reversible and the reaction becomes under thermodynamic
control to give the most stable product.
- There is NO evidence for a betaine intermediate.
- Vedejs Model:
R
Pukered (cis)
O
Ph H Cis oxaphosphetane
R
Ph P (kinetically favored)
H
Ph
H R
Planar (trans)
Ph R
oxaphosphetane
Ph P H Trans
(thermodynamically favored)
O
Ph
Phosphonate Modification (Horner-Wadsworth-Emmons)
_
R X (EtO)3P R P(OEt)2 R P(OEt)2
Arbazov Reaction O O
- R is usually restricted to EWG such as CO H, CO Me, CN, SO Ph etc. and the
2 2 2
olefin geometry is usually E.
- Still Modification TL 1983, 24, 4405.
(CF CH O) P CO Me
3 2 2 2
O
- CF CH O- groups make the betaine less stable, giving more Z-olefin.
3 2
O
Me3Si CHO (CF3CH2O)2P CO2Me Me3Si JACS 1988,
110, 2248
(Me3Si)2N- K+, THF, CO2Me
18-C-6 Z:E = 25:1
Peterson Olefination review: Synthesis 1984, 384 Organic Reactions 1990, 38 1.
- O
O
R R
1 2
R R
Me3Si CO2Me LDA, THF Me3Si _ CO2Me 1 2 Me3Si
MeO C H
Silicon can stabilize 2
an a - negative charge
O
R1 R2 - Me3Si-O R1 uofs uEa allnyd a Z m oilxetfuinres
Me Si
3 R CO Me
2 2
MeO C H
2
C=C BOND FORMATION 106
Julia-Lythgoe Olefination TL 1973, 4833 Tetrahedron 1987, 43, 1027
OH
SO Ph
2 PhO2S OTBS 1) MsCl, Et3N OTBS
LDA, THF, -78°C 2) Na(Hg), MeOH
TL 1991,
mixture
TBSO CHO of olefins 32, 495
R
R R
Tetrahedron Lett. 1993, 34, 7479
O
H O O O
1) tBuLi, THF,
HMPA, -78°C O O
O OBz 2) Na(Hg) NaHPO
4
THF, MeOH, -40°C
OBz O O
+
OSitBuPh HO OSitBuPh2 HO
2
HO
PhO S
2
O
O
O
OH
OH
OH
Milbemycin a
1
OR SmI ,
O OTBDPS HMPA/2THF O OTBDPS Synlett 1994, 859
SO Ph R= H, Ac O 75 % yield
O 2 E:Z = 3 : 1
Ramberg-Backlund Rearrangement
Br
1) Na S•Al O
2 2 3
OSiPh2tBu 2) mCPBA O S OSiPh2tBu SOCl2
OSiPh2tBu O OSiPh2tBu
Br
Cl
O OR MeLi, THF O OR - SO2 OR
S S
O OR O OR OR
thiiarane dioxide
JACS 1992, 114, 7360
Carbonyl Coupling Reactions (McMurry Reaction)
Reviews: Chem. Rev. 1989, 89, 1513.
- reductive coupling of carbonyls with low valent transition metals, Ti(0)
or Ti(II), to give olefins
O R1 R1 R1 R2 usually a mixture
"low-valent Ti" +
of E and Z olefins
R R
1 2 R R R R
2 2 2 1
excellent method for the preparation of strained (highly substituted) olefins
- Intramolecular coupling gives cyclic olefins
C=C BOND FORMATION 107
CHO
"low-valent Ti" JACS 1984, 106, 723
CHO
OMe OMe
TiCl , Zn,
4
pyridine Tetrahedron Lett. 1993, 34, 7005
OMe (86 %) OMe
OHC
O OH OH
Tebbe Reagent Cp Ti(CH )ClAlMe
2 2 2
- methylenation of ketones and lactones. The later gives cyclic enol ethers.
H
Cp C2
O O CpTiClAlMe2 O 200 °C
O
- Cp TiMe will also do the methylenation chemistry
2 2
JACS 1990, 112, 6393.
Shapiro and Related Reactions Organic Reactions 1990, 39, 1 : 1976, 23, 405
- Reaction of a tosylhydrazone with a strong base to give an olefin.
_
_
Et NNHTs2 eq. nBuLi Et N _N Ts Et N N - N2 Et _ E + Et E
THF
Me Me Me Me Me
Bamford-Stevens Reaction- initial conversion of a tosylhydrazone to a diazo
intermediate
H H H
R1 R3 base R1 R3 R1 R3
R R R
2 2 2
NNHTs N Ts +N
N_ _ N
a: aprotic- decomposition of the diazo intermediate under aprotic conditions
gives and olefin through a carbene intermediate.
H
RR12 +N R3 - N2 RR12 H ••R3 R R1 R3
2
_
N
Carbene
b. protic- decomposition of the diazo intermediate under protic conditions an
olefin through a carbonium ion intermediate.
H H
RR12 +N R3 H+ RR12 + N RH3 - N2 RR1 H R3 - H + R1 R
_ 2 + H R2 3
N N
C=C BOND FORMATION 108
b - Eliminations
Anti Eliminations
- elimination of HX from vicinal saturated carbon centers to give a olefin,
usually base promoted.
- base promoted E - type elimination proceeds through an anti-periplanar
2
transition state.
B:
H
R1 R2 R1 R2
R3 R4 R3 R4
X
- typical bases: NaOMe, tBuOK, DBU, DBN, DABCO, etc.
N N N N N
N
DBN DBU DABCO
- X: -Br, -I, -Cl, -OR, epoxides
O O
O
B: OH
R R
N
O AlEt R OH BCSJ 1979, 52, 1705
R R' 2 JACS 1979, 101, 2738
- or -
"unactivated" R'
TMS-OTf, DBU
Syn Elimination
- often an intramolecular process
H
R R
R1 R2X 1 2 X= SOe SO
R3 R4 Ph Ph
R3 R4
Cope Elimination- elimination of R NOH from an amine oxide
2
OLI + O O
MeN=CH I - O - O
2 2
NMe2 mCPBA N
THF, -78°C Me2 - Me2NOH
THF
O O NMe
2
JACS 1977,
1) Me CuLi
2 99 , 944
+ Tetrahedron
2) Me2N=CH2 1977, 35 , 613
CF CO -
3 2
C=C BOND FORMATION 109
Selenoxide Elimination Organic Reactions 1993, 44, 1.
O
NSePh R
R R' Bu3P: O R R' mCPBA H R' - ArSeOH R R' 1JA01C,S 3 7109479,
OH - or - SeAr Se
NO O SeAr
2
SeCN
H3C OH3C O PhSeO2H, H3C OH3C O
PhH, 60 °C JOC 1995, 60, 7224
H3CHN N N Ph (82%) H3CHN N N Ph JCS P1 1985, 1865
O O
Dehydration of Alcohols
- alcohols can be dehydrated with protic acid to give olefins via an E
1
mechanism.
- other reactions dehydrate alcohols under milder conditions by first converting
them into a better leaving group, i.e. POCl / pyridine, P O
3 2 5
Martin sulfurane; Ph S[OCPh(CF ) ] JACS, 1972, 94, 4997 dehydration
2 3 2 2
occurs under very mild, neutral conditions, usually gives the most stable olefin
OH
MSDA, CHCl
2 2
JACS 1989,
BzO BzO 111 , 278
H H
Burgess Reagent (inner salt) JOC, 1973, 38, 26 occurs vis a syn elimination
_ +
MeO CNSO NEt
2 2 3
MeO C
2
H R3R MeO2CN_SO2N+Et3 H-N SOO2 R1 R4
4
R
1 PhH, reflux
R2 OH R1R RR4 R2 R3
2 3
Olefins from Vicinal Diols
Corey-Winter Reaction JACS 1963, 85, 2677; TL 1982, 1979; TL 1978, 737
S
OH
R' Im2C=S O O R3P:
R
R R'
OH R R'
C=C BOND FORMATION 110
- vic-diols can be converted to olefins with K WCl JCSCC 1972, 370; JACS
2 6
1972, 94, 6538
- This reaction worked best with more highly substituted diols and give
predominantly syn elimination.
- Low valent titanium; McMurry carbonyl coupling is believed to go through
the vic-diol. vic-diols are smoothly converted to the corresponding olefins under
these conditions. JOC 1976, 41 , 896
Olefins from Epoxides
O Ph2P - HO H R2 MeI HO H R2
R1 H R2H R1 H PPh2 R1 H P+Ph2Me
+
HO PPh2Me -Ph2MeP=O R1 R2 "inversion "
R2 H of R groups
H H
R H
1
NCSe Se -
O NC-Se- - O H R2
R1 H R H SeCN - OR2 H NCOR2 H
H R2 1 R1 H R1 H
NCO H R2 R1H R2H R1 H "retention"
R1 H Se - Se H R2 of R groups
From Acetylenes
- Hydrogenation with Lindlar's catalyst gives cis-olefins
H , Rh
R R' Co2(CO)8 R R' 2
R R'
Co (CO)
2 6
Bu SnH
3
Tetrahedron Lett. 1998, 39, 2609
H SnBu
3
R R'
From Other Olefins
Sigmatropic Rearrangements
- transposition of double bonds
Birch Reduction Tetrahedron 1989, 45, 1579
OMe OMe O
H O+
3
C=C BOND FORMATION 111
Olefin Isomerization- a variety of transition metal (RhCl •H O) catalyst will
3 2
isomerize doubles bonds to more thermodynamically favorable configurations
(i.e. more substituted, trans, conjugated)
RhCl •3H O
3 2 JOC 1987,
EtOH 52 , 2875
OH OH
Cl Cl
Ti
+ JACS 1992
114 , 2276
up to 80% ee
Olefin Inversion Tetrahedron 1980, 557
- Conversion of cis to trans olefins
- Conversion of trans to cis- olefins
R R' hn , PhSSPh R
R'
OH
OH
I, CHCl
CO2Me 2 2 2 HO
CO Me
C H OH 2
5 11
C H OH
5 11
OH JACS, 1984, 107, xxxx
Transition Metal Catralyzed Cross-Coupling Reactions
Coupling of Vinyl Phosphonates and Triflates to Organometallic Reagents
- vinyl phosphates review: Synthesis 1992, 333.
O OP(OEt)
2
Li, NH ,
3
R2CuLi tBuOH
R R
O O O
(EtO)2PCl R2CuLi
O OP(OEt)2 R
- preparation of enol triflates Synthesis 1997, 735
O
OTf
LDA, THF, -78°C
kinetic
product
Tf NPh
2
O OTf
Tf O, CH Cl
2 2 2 thermodynamic
product
tBu N tBu
C=C BOND FORMATION 112
- reaction with cuprates. Acc. Chem. Res. 1988, 25, 47
OTf Ph
Ph CuLi TL 1980,
2 21 , 4313
tBu tBu
- palladium (0) catlyzed cross-coupling of vinyl or aryl halides or triflates with
organostannanes (Stille Reaction)
Angew. Chem. Int. Ed. Engl. 1986, 25, 508.; Organic Reactions 1997, 50, 1-652
SnMe
O 3 O
1)LDA, Tf NPh
2 JOC 1986,
O 2) Pd(PPh3)4 O 51 , 3405
O
OH
OTBS BuSn
3
I I
Bu3Sn O OH
O O J. Am. Chem. Soc.
OH
1998, 120, 3935
HO
TBSO
HO Bu3Sn
TBSO I
(-)-Macrolactin A
BOMe
TESO 1) O , Me S
CHO 1) 2) al3lyl bro2mide, Zn TBSO OH 1) HF, MeCN
2 2) Me4NBH(OAc)3
MgBr 3) Dess-Martin 3) TBSCl, imidazole
Periodinane (76%)
2) TESOTf, 2,6-lutidine (70%)
(52%)
a) nBu SnH,
TESO TESO O , NaBH TESO OTES (Ph P)3PdCl TESO OTES
3 4 3 2 2
(77%) OH b) I2 I OH
(83%
OPiv OH I
1) Dess-Martin
Periodinane
OPiv 2) Ph3P+CH2I, I- OH
BuSn NaHMDS
3
TBSO
TBSO
3) DIBAL
PdCl (MeCN)
2 2 TBSO (50%) TBSO
I
TESO TESO
Bu3SnCHBr2, CrCl2 CO2H TESO
CHO SnBu
3
(42%) PdCl (MeCN)
2 2
(65%)
CO H
2
Bu SnH, AIBN TESO I
3
(38%) Bu3Sn
CO H
2