Synthesis with enolate

Notes Chemistry

Word count: 387Reading time: 2 min

 2020/01/11   Share

A brief note on the use of enolates in syntheses.

Enolate alkylation

Condition overview

By electrophile

Electrophile type	Conditions	Note
Activated R-X	Best with enamines 1. $\ce{R2NH},\ \rm{cat\ }\ce{H+}$ 2. $\ce{R-X}$ 3. $\ce{H+}$
Tertiary R-X	Lewis acid to form cation $\ce{TiCl4}$ , TMS enol ether one pot	Also $2^\circ$ if preferred

By enol(ate)

Enol(ate) type	Conditions	Note
Ketone, ester, carboxylic acid	LDA, $-78^\circ\rm{C}$ , THF
Nitro, nitrile	$\ce{OH-}$ , one pot with phase separating conditions e.g. $\ce{BnEt3N+Cl-}$
Aldehydes	Aza-enolate 1. $\ce{t-BuNH2}$ , cat $\ce{H+}$ 2. LDA, $-78^\circ\rm{C}$ , THF 3. $\ce{H+}$	Can’t use LDA directly
$\beta$ -dicarbonyl	One-pot with $\ce{NaOH}$ .	To remove, decarboxylate. $\ce{NaOH}$ then $\ce{H+ / H2O}$ to yield acid; $\ce{NaCl}$ heat for ester.

Regioselectivity

For more substituted side,

Substrate	Condition	Note
Single carbonyls	1. $\ce{TSMCl}$ , $\ce{Et3N}$ 2. $\ce{MeLi}$ 3. R-X	No need MeLi for Sn1 electrophiles.
Enones	Dissolved metal - only alkylate at the conjugated side 1. $\ce{Li}$ , $\ce{NH3}$ 2. R-X
$\beta$ -dicarbonyl	Alkylate in the middle twice, then decarboxylate.

For less substituted side,

Substrate	Condition	Note
Single carbonyls	LDA	Aza-enolate for aldehyde; Change to TMS enol-ether if needed.
$\beta$ -dicarbonyl	1. Alkylate di-anion 2. Alkylate in the middle twice.
Activated R-X	Enamine

Aldol reactions

Notes

In acidic conditions, condensation product is usually given (via E1).
For cross condensation, make sure
1. Only 1 species enolisable,
2. Electrophile is more electrophilic than enolisable carbonyl.

Choices

By electrophile

Non-enolisable groups next to the carbonyl:

H
tert-alkyl
tri-substituted
Ar
heteroatoms

For formaldehyde, Mannich reagent must be used.

By enolate

Nitro-compounds - not electrophilic, easily enolised.
Use SSE -
- LDA
- TMS enol ether: need $\ce{TiCl4}$ catalyst, and $\ce{H2O}$ work-up.
- Conjugated Wittig reagent: (aka stabilised ylid) gives trans-alkene.
- $\beta$ -dicarbonyl: one-pot mixture of weak base in weak acid buffer, e.g. $\ce{R2NH}$ , $\ce{AcOH}$ .
Special choices

Enolate	Equivalent
Ester	Zn enolate: no reactions with esters.
Aldehyde	Aza-enolate instead of LDA.

Claisen reactions

Choices

Non-enolisable electrophile

Decreasing reactivity:

EtOCOCOOEt > HCOOEt > EtOCOOEt

SSE

Li, Mg and Zn enolates as above all OK, except
- Need aza-enolate for aldehydes
- No BuLi with carboxylic acids - LDA OK
Enamine only reacts well with RCOCl
$\ce{BF3}$ can be used for enolisation

Like this? Please support me!

or via other methods.

Author：2LalA猪

Permalink：https://butteraddict.fun/2020/01/Synthesis-with-enolate/

Published on：11th January 2020, 9:42 am

Updated on：9th June 2020, 3:21 pm

License：CC BY 4.0

Next Post

Theoretical Techniques Key Equations
Previous Post

High Resolution Spectroscopy

Webmentions - no interactions yet...

CATALOG

1. Enolate alkylation
1. 1.1. Condition overview
2. Aldol reactions
1. 2.1. Notes
2. 2.2. Choices
  1. 2.2.1. By electrophile
  2. 2.2.2. By enolate
3. Claisen reactions
1. 3.1. Choices
  1. 3.1.1. Non-enolisable electrophile
  2. 3.1.2. SSE



缺失模块。
1、请确保node版本大于6.2
2、在博客根目录（注意不是archer根目录）执行以下命令：
npm i hexo-generator-json-content --save
3、在根目录_config.yml里添加配置：

jsonContent:
  meta: false
  pages: false
  posts:
    title: true
    date: true
    path: true
    text: false
    raw: false
    content: false
    slug: false
    updated: false
    comments: false
    link: false
    permalink: false
    excerpt: false
    categories: true
    tags: true