Felkin规则和Cram规则 不对称诱导(4)

conformation, and the nucleophile will then attack from the side with the smallest free α-carbon substituent.[12] If the chelating R group is identified as the largest, this will result in an \product.

This stereoselective control was recognized and discussed in the first paper establishing the Cram model, causing Cram to assert that his model requires non-chelating conditions.[13] An example of chelation control of a reaction can be seen here, from a 1987 paper that was the first to directly observe such a \[14] vindicating the model:

Here, the methyl titanium chloride forms a Cram-chelate. The methyl group then dissociates from titanium and attacks the carbonyl, leading to the anti-Felkin diastereomer.

A non-chelating electron-withdrawing substituent effect can also result in anti-Felkin selectivity. If a substituent on the α-carbon is sufficiently electron withdrawing, the nucleophile will add anti-

relative to the electron withdrawing group, even if the substituent is not the largest of the 3 bonded to the α-carbon. Each model offers a slightly different explanation for this phenomenon. A polar effect was postulated by the Cornforth model[15] and the original Felkin model,[16] which placed the EWG substituent and incoming nucleophile anti- to each other in order to most effectively cancel the dipole moment of the transition structure.

This Newman projection illustrates the Cornforth and Felkin transition state that places the EWG anti- to the incoming nucleophile, regardless of its steric bulk relative to RS and RL.

The improved Felkin–Anh model, as discussed above, makes a more

sophisticated assessment of the polar effect by considering molecular orbital interactions in the stabilization of the preferred transition state. A typical reaction illustrating the potential anti-Felkin selectivity of this effect, along with its proposed transition structure, is pictured below:

Carbonyl 1,3 asymmetric induction[edit]

It has been observed that the stereoelectronic environment at the

β-carbon of can also direct asymmetric induction. A number of predictive models have evolved over the years to define the stereoselectivity of such reactions.

Chelation model[edit]

According to Reetz, the Cram-chelate model for 1,2-inductions can be extended to predict the chelated complex of a β-alkoxy aldehyde and metal. The nucleophile is seen to attack from the less sterically hindered side and anti- to the substituent Rβ, leading to the anti-adduct as the major product.[17]

To make such chelates, the metal center must have at least two free coordination sites and the protecting ligands should form a bidentate complex with the Lewis acid.

Non-chelation model[edit] Cram–Reetz model[edit]

Cram and Reetz demonstrated that 1,3-stereocontrol is possible if the reaction proceeds through an acyclic transition state. The reaction of β-alkoxy aldehyde with allyltrimethylsilane showed good selectivity for

the anti-1,3-diol, which was explained by the Cram polar model. The polar benzyloxy group is oriented anti to the carbonyl to minimize dipole interactions and the nucleophile attacks anti- to the bulkier (RM) of the remaining two substituents.[18][19]

Evans model[edit]

More recently, Evans presented a different model for nonchelate

1,3-inductions. In the proposed transition state, the β-stereocenter is oriented anti- to the incoming nucleophile, as seen in the Felkin–Anh model. The polar X group at the β-stereocenter is placed anti- to the carbonyl to reduce dipole interactions, and Rβ is placed anti- to the aldehyde group to minimize the steric hindrance. Consequently, the 1,3-anti-diol would be predicted as the major product.[20]

Carbonyl 1,2 and 1,3 asymmetric induction[edit]

If the substrate has both an α- and β-stereocenter, the Felkin–Anh rule (1,2-induction) and the Evans model (1,3-induction) should considered at the same time. If these two stereocenters have an anti- relationship, both models predict the same diastereomer (the stereoreinforcing case).