The Krama rule is a rule for predicting the stereoselectivity of nucleophilic attachment to a carbonyl group located near the chiral center (1,2-asymmetric induction). It was first formulated by Donald James Crum in 1952 due to the generalization of experimental data available at that time [1] .
Content
Models
The Kram rule is based on the concepts of the conformation of carbonyl compounds and the nature of the substituents at the chiral carbon atom. It involves the following assumptions:
- the compound is in such a conformation in which the oxygen atom of the carbonyl group is located between the small (R S ) and medium-sized (R M ) substituents at the chiral carbon atom;
- the approach of the reagent – nucleophile to the carbonyl group is possible on both sides, but it is mainly carried out on the side of the smaller substituent R S [2] .
Such a model is applicable only to carbonyl compounds with non-polar substituents. If the adjacent chiral center contains a hydroxyl, alkoxy or amino group that can provide a coordination bond with the counterion of the nucleophilic reagent, then another model, the Krama model with chelation proposed in 1959, should be used. It is distinguished by the fact that in this case the polar substituent X and the carbonyl group are in a blocked position, and the attack of the nucleophile is accomplished with the least steric obstacles from the lesser substituent [1] .
Disadvantages
The Krama model turned out to be based on simplified and incorrect premises, but at one time it served as a good tool for predicting the stereochemistry of nucleophilic addition reactions and demonstrated the fundamental possibility of explaining the results obtained using fairly simple considerations [2] .
The Krama model contained significant flaws:
- within the framework of this model, the conformations of the initial compound and the transition state were identified;
- the conformation of the substrate was erroneously represented (a conformation in which the most bulky substituent and the carbonyl group are in a mutually perpendicular position) is advantageous;
- The possibility of the reaction was considered incorrectly only for one conformational state of the substrate (in fact, conformational transitions that have a lower activation energy than the reaction itself are possible) [2] .
At present, other models are used for the case of 1,2-asymmetric induction (mainly the Felkin-Ana model) [1] .
See also
- Rule Felkin - Ana
- Chelation Model
Notes
- 2 1 2 3 Cram's Rule // Comprehensive Organic Name Reactions and Reagents. - John Wiley & Sons, 2010. - DOI : 10.1002 / 9780470638859.conrr167 .
- 2 1 2 3 Smith, Dilman, 2009 , p. 148-149.
Literature
- Cram DJ, Abd Elhafez FA Studies in Stereochemistry. X. The Rule of “Steric Control of Asymmetric Induction” in the Syntheses of Acyclic Systems (Eng.) // J. Am. Chem. Soc. - 1952. - Vol. 74 , no. 23 . - P. 5828-5835 . - DOI : 10.1021 / ja01143a007 .
- Smith, V.A., Dilman, A.D. Chapter 6.6.1. Krama's rule // Basics of modern organic synthesis. - M .: Bean. Laboratory of Knowledge, 2009. - 750 p. - ISBN 978-5-94774-941-0 .