Felkin规则和Cram规则 不对称诱导(2)

catalyst of chiral ligand. This method of asymmetric synthesis is economically most desirable.

Contents

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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:

The Felkin rules are:

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The transition states are reactant-like.

Torsional strain (Pitzer strain) involving partial bonds (in transition states) represents a substantial fraction of the strain between fully formed bonds, even when the degree of bonding is quite low. The conformation in the TS is staggered and not eclipsed with the substituent R skew with respect to two adjacent groups one of them the smallest in TS A.

For comparison TS B is the Cram transition state.

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The main steric interactions involve those around R and the nucleophile but not the carbonyl oxygen atom.

A polar effect or electronic effect stabilizes a transition state with maximum separation between the nucleophile and an electron-withdrawing group. For instance haloketones do not obey Cram's rule, and, in the example above, replacing the electron-withdrawing phenyl group by a cyclohexyl group reduces stereoselectivity considerably.

Felkin-Anh model[edit]

The Felkin-Anh model[5] is an extension of the Felkin model that

incorporates improvements suggested by Nguyen T. Anh and O. Eisenstein to correct for two key weaknesses in Felkin's model. The first weakness addressed was the statement by Felkin of a strong polar effect in nucleophilic addition transition states, which leads to the complete inversion of stereochemistry by SN2 reactions, without offering

justifications as to why this phenomenon was observed. Anh's solution was to offer the antiperiplanar effect as a consequence of asymmetric

induction being controlled by both substituent and orbital effects.[6][7] In this effect, the best nucleophile acceptor σ* orbital is aligned parallel to both the π and π* orbitals of the carbonyl, which provide stabilization of the incoming anion.

The second weakness in the Felkin Model was the assumption of substitu …… 此处隐藏：4056字，全部文档内容请下载后查看。喜欢就下载吧 ……