Cahn-Ingold-Prelog priority

Cahn-Ingold-Prelog Priority Rules (Table 5 1, p 175)... 

Assign Cahn-Ingold-Prelog priorities to the following sets of substituents ... 

To avoid potential uncertainties in the application of the Cahn-Ingold-Prelog priority rules, by convention the enolate oxygen is assigned the higher priority. 

Deprotonation of OJ-alkylated acetic acid esters (e. g., the propionic acid ester of Figure 13.16) with LDA at-78 °C selectively yields the "if "-enolates. The quotation marks indicate that this application of the term is based on an extension of the /f/X-n omencIature here, the Cahn-Ingold-Prelog priority of the 0 Li substituent is considered to he higher than the priority of the OR group. The deprotonation of the ester shown in Figure 13.16 occurs via the strain-free transition state A. The alternative transition state B is destabilized by a 1,3-diaxial interaction. 

Fig. 13.46. Explanation of the anti-selectivity of the Ivanov reaction of Figure 13.45 by means of the Zimmerman-Traxler model. The stereodescriptors Re and Si are defined as follows. Suppose you are looking down on the plane of an alkene, in which an sp2-hybridized C atom is connected to three different substituents. You are on the Re side of the double bond if the Cahn-Ingold-Prelog priorities of these substituents decrease going clockwise, and on the Si side otherwise.

Re-face, Si-face a face of a trigonal atom is designated Re if the ligands of the trigonal atom appear in a clockwise sense in order of CIP (Cahn-Ingold-Prelog) priority when viewed from that side of the face. The opposite arrangement is termed Si. 

Notice that Cahn-Ingold-Prelog priority interchange accompanies each of the chemical conversions of the Mosher acid (MTPA-OH) to Mosher acid chloride (MTPA-CI) to Mosher ester (MTPA-OR). This is a particuiariy crucial detail since both enantiomers of MTPA-CI as well as of MTPA-OH are now commercially available. 

Assign Cahn-Ingold-Prelog priorities to the following sets of substituents (a) — CH = CH2. — CHiCHala, — (XCHala, — CH2CH3... 

It should be obvious that the cis isomer is usually also the (Z) isomer, while the trans isomer is usually also the (E) isomer. This useful arrangement is not foolproof, however, and the anticancer drug tamoxifen is a notable example of a drug that is trans with respect to the phenyl groups, but also (Z) when the Cahn-Ingold-Prelog priorities are used (Figure 4.17). 

The Cahn-Ingold-Prelog priorities of the groups are the circled numbers in (a). 

The absolute configuration system stems from the Cahn-Ingold-Prelog priority rules, which allow a precise description of a stereocenter without using any reference compound. In fact the basis is now the atomic number of the stereocenter substituents. 

Fio. 2. Application of the Cahn-Ingold-Prelog priority sequence system to mark tlie C-17 stereochemistry in the absence and presence of the COOCH3 substituent. 

We will normally use the view on the left hand side for square planar (octahedral) and tetrahedral geometries around the optically active atom. The second view for a tetrahedral geometry shows the numbering scheme according to the Cahn, Ingold, Prelog priority rules whereas the third view shows that a tetrahedron consists of two pairs of substituents that are in planes perpendicular to each other. 

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