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.

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

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

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