Wittig-type Reactions - Larock p. 327-350 1,2-Disubstituted Olefins Metathesis Reactions - Grubbs group Tri & Tetrasubstituted olefins (see other handout) Elimination Reactions - Larock p. 251-315 Terminal Olefins (see other handout) O R' R R R R R Y X R R 3 P R'' R''' R' R R R R R' R R'' R''' R' R R R R R R R R R R R R R R reagent + E Z + Catalyst Olefin Synthesis -Plethora of references in the literature on olefin synthesis: see Larock 2 nd ed. p. 215-562 -These can be catagorized by reaction type: -Or categorized by the olefinic product: Chem 6352 Jeremy May Note: these are much more difficult because of E/Z issues! IV III II I R R H N N H Cr CO CO CO HBR 2 H R R BR 2 R R OMe AcOH CO 2 Me OH R R H R R H 1,2-Disubstituted Olefins •Z-olefins Lindar's Catalyst, H 2 Diimide reduction , H 2 (JOC 1985, 30, 1147) Hydroboration/Acidic Quench - F r o m A c e t y l e n e s: by reduction - F r o m R i n g s: O 3 , NaBH 4 Pd/BaSO 4 , Quinoline (partially poisons catalyst)
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Wittig-type Reactions - Larock p. 327-350 1,2-Disubstituted Olefins
Metathesis Reactions - Grubbs group Tri & Tetrasubstituted olefins (see other handout)
Elimination Reactions - Larock p. 251-315 Terminal Olefins (see other handout)
O
R'
R
RRR R
YX
R
R3P
R''
R'''
R'
R
RR
R
R'
R
R''
R'''R'
R
R
R
R
RR
R
R
R
R R
R
RR
reagent
+E Z
+Catalyst
Olefin Synthesis
-Plethora of references in the literature on olefin synthesis: see Larock 2nd ed. p. 215-562
-These can be catagorized by reaction type: -Or categorized by the olefinic product:
Chem 6352Jeremy May
Note: these are much more difficult because of E/Z issues!
IV
III
II
I
R R
H N N H
Cr
CO
CO
CO
HBR2
H
R R
BR2
RR
OMe
AcOH
CO2Me
OH
R R
H
R R
H
1,2-Disubstituted Olefins
•Z-olefins
Lindar's Catalyst, H2
Diimide reduction
, H2 (JOC 1985, 30, 1147)
Hydroboration/Acidic Quench
-From Acetylenes: by reduction
-From Rings:
O3, NaBH4
Pd/BaSO4, Quinoline (partially poisons catalyst)
S+
-
O-
P
O
PhPh
Ph
H
HR
R'
Base: nBuLi, LDA, KHMDS, NaHMDS, LiHMDS, tBuOK, , etc.
(DMSO, NaH)
R X
R PPh3
PPh3
O
R'
H
H
Ph3P
RC HPh3P
R
OH
R
R PPh3
R PPh3 X
H H
R' H
O
C HPh3P
R
OH
R'
R H
HR'
R R'
Ph3P O
R PPh3
OH
R'
Ph3PH
R
-From Wittig Reaction:
preparation of ylide:
+Δ
Polar Solvent(THF, acetone, EtOH, MeCN)
pKa ~22
base
mechanism of the Wittig reaction: Chem. Rev. 1989, 863 JACS 1989, 6861 JACS 1981, 2823
Antiperiplanar
Kinetic Reaction Preference Betaine
Oxaphosphetaine
+
Vedejs
alkyl halide
R H
OLi
R H
O
Ph3P
Ar
H
I I
R H
O
Ph3P
H
I
PPh3
P
Ar
H
O
MeO
R H
O
R Ar
R Ar
R I
RAr
RAr
N
N
LiN
N
-Salt Effect:
Activation of the carbonyl by a Lewis acidic salt can increase the reaction rate and lower the selectivity. Also, it leads to a more open transition state (ie. there are fewer steric effects).
-To counter the effect:
Additives: HMPA, TMEDA → these break up and sequester lithium ions
Conditions control the stereospecificity of the elimination reaction, but the initial stereochemistry of the addition to the carbonyl must also be controlled to produce E or Z olefins specifically.
Tetrahedron 1994, 50, 6643
90% yield13:1 E:Z
For practice:What is the required stereochemistry for each step of the mechanism?
2,3 and 3,3 rearrangements (eg Wittig, Claisen, Cope, etc.)In fact 3,3 rearrangements are among the best methods.
Wittig Rxns: Typically not very selective (if R' and R'' are different).some examples with stabilized reagents: Kishi TL 1981, 37, 3873JACS 1979, 101, 259