Felkin规则和Cram规则 不对称诱导

费尔金

-

安过渡态模型

（

Felkin-Anh

模型

）是一个 用来解释

α

-

手性酮亲核加成

反应中产物的立体选择性现象的理论模型。是对

克莱姆模型

（

Cram

规则）的发

展。

历史

该模 型由费尔金在

1960

年代提出。

19 76

年经安和埃森斯坦修正后得名，故有时

也称费尔金

-

安

-

埃塞斯坦模型。 费尔金是

法国化学家

，

安

是一个姓阮（

Nguy

?

n

Tr

?

ng ?nh/Anh，阮仲映

/

英

/

婴？） 的旅法越南化学家。

模型图示

如图

纽曼投影式

所示。

亲核试剂

从左侧进攻

羰基

。

手性

碳上的最大基团与

羰基

< br>碳

氧键保持垂直。基团大小由

CPI

规则

确定。

Felkin

规则和

Cram

规则说的是同一件事，

Felkin

规则是

Cram

规则 的发展，更

准确。适用条件是

C=O

的

a-C

是手型的。

Cram I

：

如果在

C=O

的

α

-C

联 有三个体积不同的基团，就会造成羰基平

面两侧的空间阻碍不同，

给亲核试剂进攻羰基创造了空间上的选择性，

我们用

L

、

M

、

S

分别表示

α

-C

上体积大、中、小的三个基团，规则如图所示。

Cram II

：规则二适用于当

α

-C

上有

-OH

，

-NHR

之类的基团从而和羰基氧

形成氢键的情况。

本情况下，

应该取重叠式构象为最稳构象，< /p>

亲核试剂从

S

侧进

攻。

Cram

法则

Felkin-Ahn and Chelation Control

In Felkin-Ahn model, a nucleophile comes from the least hindered side. The

best way to do Felkin-Ahn model is to draw a newmen projection. Then

have the nucleophile attack from the smallest group.

Felkin-Ahn model example:

Here, the model shows that the nucleophile prefers to attack from the least

hindered side.

Chelation Control:

In

Chelation

Control

there

is

always

a

lewis

base

or

lewis

acid

is

present.

Example: Lewis Bases are OR', NR2' or SR' and lewis acids are Li+, MgX+,

Zn+2.

Since

lewis

base

is

present

the

double

bonded

oxygen

and

lewis

base

form a ring with lewis acid.

Chelation Control example:

Next slide shows that when a Lewis-base or Lewis-Acid is present,

Chelation

Control

gives

the

major

product,

by

forming

a

ring

in

transition

state and Felkin-Ahn models fails.

In General: How to choose between

Felkin-Ahn and Chelation Control:

Asymmetric induction

(also

enantioinduction

) in

stereochemistry

describes the preferential formation in a

chemical reaction

of one

enantiomer

or

diastereoisomer

over

the

other

as

a

result

of

the

influence

of a

chiral

feature present in the

substrate

,

reagent

,

catalyst

or

environment.

[1]

Asymmetric induction is a key element in

asymmetric

synthesis

.

Asymmetric

induction

was

introduced

by

Hermann

Emil

Fischer

based

on

his

work on

carbohydrates

.

[2]

Several types of induction exist.

Internal asymmetric induction

makes use of a chiral center bound to the

reactive

center

through

a

covalent

bond

and

remains

so

during

the

reaction.

The starting material is often derived from

chiral pool synthesis

. In

relayed asymmetric induction

the chiral information is introduced in a

separate

step

and

removed

again

in

a

separate

chemical

reaction.

Special

synthons

are

called

chiral

auxiliaries

.

In

external

asymmetric

induction

chiral information is introduced in the

transition state

through a

catalyst

of

chiral ligand

. This method of

asymmetric synthesis

is

economically most desirable.

Contents

[

hide

]

?

?

?

?

?

?

?

1 Carbonyl 1,2 asymmetric induction

o

1.1 Cram's rule

o

1.2 Felkin model

o

1.3 Felkin-Anh model

o

1.4 Anti

–

Felkin selectivity

2 Carbonyl 1,3 asymmetric induction

o

2.1 Chelation model

o

2.2 Non-chelation model

o

2.3 Cram

–

Reetz model

o

2.4 Evans model

3 Carbonyl 1,2 and 1,3 asymmetric induction

4 Acyclic alkenes asymmetric induction

5 See also

6 References

7 External links

Carbonyl 1,2 asymmetric induction[

edit

]

Several models exist to describe chiral induction at carbonyl carbons

during nucleophilic additions. These models are based on a combination

of steric and electronic considerations and are often in conflict with

each other. Models have been devised by Cram (1952), Cornforth (1959),

Felkin (1969) and others.

Cram's rule[

edit

]

The

Cram's rule of asymmetric induction

developed by

Donald J. Cram

in

1952

[3]

is an early concept relating to the prediction of stereochemistry

in certain

acyclic

systems. In full the rule is:

In certain non-catalytic reactions that diastereomer will predominate,

which

could

be

formed

by

the

approach

of

the

entering

group

from

the

least

hindered side when the rotational conformation of the C-C bond is such

that the double bond is flanked by the two least bulky groups attached

to the adjacent asymmetric center.

The

rule

indicates

that

the

presence

of

an

asymmetric

center

in

a

molecule

induces the formation of an asymmetric center adjacent to it based on

steric hindrance

.

In his 1952 publication Cram presented a large number of reactions

described in the literature for which the conformation of the reaction

products could be explained based on this rule and he also described an

elaborate experiment (

scheme 1

) making his case.

The experiments involved two reactions. In experiment one

2-phenylpropionaldehyde

(

1

,

racemic

but (R)-enantiomer shown) was

reacted with the

Grignard reagent

of

bromobenzene

to

1,2-diphenyl-1-propanol

(

2

)

as

a

mixture

of

diastereomers

,

predominantly

the

threo

isomer

(see for explanation the

Fischer projection

).

The preference for the

formation of the

threo isomer can

be explained by

the rule stated above by having the active

nucleophile

in this reaction

attacking the

carbonyl group

from the least hindered side (see

Newman

projection

A

) when the carbonyl is positioned in a

staggered

formation

with the

methyl

group and the

hydrogen

atom, which are the two smallest

substituents

creating a minimum of

steric hindrance

, in a

gauche

orientation

and

phenyl

as

the

most

bulky

group

in

the

anti

conformation

.

The

second

reaction

is

the

organic

reduction

of

1,2-diphenyl-1-propanone

2

with

lithium aluminium hydride

, which results in the same reaction

product

as

above

but

now

with

preference

for

the

erythro

isomer

(

2a

).

Now

a

hydride

anion

(H

?

)

is

the

nucleophile

attacking

from

the

least

hindered

side (imagine hydrogen entering from the paper plane).

In the original 1952 publication, additional evidence was obtained for

the structural assignment of the reaction products by applying them to

a

Chugaev

elimination

,

wherein

the

threo

isomer

reacts

to

the

cis

isomer

of -

α

-methyl-

stilbene

and the erythro isomer to the trans version.

Felkin model[

edit

]

The

Felkin model

(1968) named after

Hugh Felkin

also predicts the

stereochemistry

of

nucleophilic

addition

reactions

to

carbonyl

groups.

[4]

Felkin

argued

that

the

Cram

model

suffered

a

major

drawback:

an

eclipsed

conformation in the

transition state

between the carbonyl substituent

(the

hydrogen

atom

in

aldehydes)

and

the

largest

α

-carbonyl

substituent.

He demonstrated that by increasing the steric bulk of the carbonyl

substituent from

methyl

to

ethyl

to

isopropyl

to

isobutyl

, the

stereoselectivity

also

increased,

which

is

not

predicted

by

Cram's

rule: