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Cram’s Rule CX * diastereomeric faces X = C, O, N stereogenic center How does this center control The direction of attack at The trigonal carbon?

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Presentation on theme: "Cram’s Rule CX * diastereomeric faces X = C, O, N stereogenic center How does this center control The direction of attack at The trigonal carbon?"— Presentation transcript:

1 Cram’s Rule CX * diastereomeric faces X = C, O, N stereogenic center How does this center control The direction of attack at The trigonal carbon?

2 R M S L O L RNu OH M S L NuR OH M S Nu: Less steric effects Major product Nu: Minor product O MS R L

3 R M S L O L M S R O L S M R O This is the important interaction that must be minimized. Thus, in this approach the carbonyl substituent plays the major role. Favored Conformer for Attack The interpretation of Felkin and Anh

4 Bürgi-Dunitz trajectory 109° Obtuse attack trajectory minimizes unfavorable interactions between these orbitals CO R M L S s p* Nu Houk computational view:

5 The obtuse angle of attack supports the nonpassive role of the R-group in ketones. Not only will there be steric interactions between the S or M groups and the R-group, but also interactions with the incoming nucleophile due to the attack trajectory. In this model one would predict an increase of stereodifferentiation as the size of R increases. This has been found experimentally

6 A useful orbital approach by Cieplak, suggests that the nucleophile will attack the carbonyl anti to the best donor ligand. A.S. Cieplak, B.D. Yait and C.R. Johnson, J. Am. Chem. Soc., (1989), 111, 8447 A.S. Cieplak, J. Am. Chem. Soc., (1981), 103, 4548. Donor O s * of nucleophile Carbon donor s-bond Nu: E

7 Cases for Modification of the Models Compare the "normal" situation with the influence of a sterically bulky Lewis acid L S M O H O H S M L Lewis acid Nu: As the bulk of the Lewis acid increases Lewis acid :Nu This gives the Cram product This gives the "anti-Cram" product

8 Dipolar Model often described as the Cornforth model

9 Chelation Control See: M.T. Reetz, Acc. Chem. Res., (1993), 26, 462. R L S Het O M Preferred direction of attack Het = heteroatom M = metal L S Het O R M

10 Predict a product from the following reaction

11 A potentially useful extension of Cram's rule is the asymmetric induction provided by a remote ester (Prelog's rule): R O L O O S M R'MgX Why would you think this might not provide as important directing influences?

12 Explain the following trends observed by Midland and coworkers M.M. Midland and Y.C. Kwon, J. Am. Chem. Soc. (1983), 105, 3725. H Me O Me H Me Me OH H H Me Me H OH H H H NaBH 4 Sia 2 BH G G 5 : 1 1 : 10 Ratio

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