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Massachusetts Institute of TechnologyOrganic Chemistry 5.511
October 17, 2007Prof. Rick L. Danheiser
Unit 2: Carbanionic Synthons
Lecture 5
Reading Assignment
Background: Clayden et al. Sections of Chapters 9, 21, and 26
Carey and Sundberg Part B, Chapters 1, 7 (Sections 7.1, 7.2, and 7.3.1), and 8 (Section 8.1) Note: some stereochemical features of this chemistry will not be covered until later units
C
C Met
C C
C COH
C C
O
R
C CC
EWG
C X
C O
RC O
Xδ−
C CEWG
δ+
carbanion
polar organometallic
Alkylationand
Cross-Coupling
Aldol, Wittig,etc.
Acylation,Claisen,
Dieckmann,etc.
ConjugateAddition,Michael
X = halide, OTs, OMs, OTf OAc, OR, epoxide
ketones, aldehydes
X = Cl, OR, OCOR, etc.
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pKa Values for Some Typical Carbon Acids
1. Metalation with base (deprotonation) 2. Oxidative addition (reductive metalation) 3. Halogen-metal exchange 4. Transmetalation 5. Addition to π-bonds 6. Fragmentation and cleavage
Introduction to General Reactivity and Overview ofGeneral Methods for the Generation of Carbanionic Synthons
Unit 2 Outline
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pKa Values for Some Common Bases
NH
N
N N
N
TMP2,2,6,6,-tetramethylpiperidine
DABCO1,4- Diazabicyclo[2.2.2]octane
DBU1,8-Diazabicyclo[5.4.0]undec-7-ene
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XR
O
N H
O
Li
L
L
R
X
H
N H
O
Li
L
L
H
X
R
E Z
vs.LiNL2
Transition StateModels for
Kinetic Deprotonation
X
R
OLi
HX
H
OLi
R
E(O) Enolate Z(O) Enolate
OR
O
OR
OLi
OR
OLi+
O OLi OLi
+
LDA, THFLDA, THF-HMPA
95 510-15 85-90
LDA, THFLiTMP, THFLiHMDS, THFLiN(SiMe2Ph)2
77 2386 1434 66 0 100