CIP rules for

Early implementations of the CIP rules for computer detection and specification of chirality were described for the LHASA [105], CHIRON [106], and CACTVS [107] software packages. Recently, several commercial molecular editors and visualizers (e.g., CambridgeSoft s ChemOffice, ACD s I-Lab, Accelrys WebLab, and MDL s AutoNom) have also implemented the CIP rules. 

Scheme 7.10. Titanocene catalyzed asymmetric reduction of imines [85], In the accompanying discussion, the catalyst shown is designated the S,S enantiomer, in accord with the CIP rules for describing metal arenes [88]. This is a different designation than that used by Buchwald, however. ...

As noted above, synthetically important prochiral centers are the carbonyl of a ketone or aldehyde and the double bond of an alkene. These functional groups do not contain a pro-R or pro-S group but it is clear that delivery of a fourth point ligand from one face or the other will lead to an (R) or (5) chiral center, as in conversion of 108 to 109 and/or 110. If the carbonyl is oriented as in ketone lllA, priorities can be assigned to the three atoms connected to the prochiral atom, based on the CIP rules. For lllA, the a b c priority is... 

CIP rules for prioritizing substituents, groups, and atoms (Chapter 9, Section 9.3)... 

Application of the CIP rule for the determination of the absolute configuration of an epoxide. 

The Cahn-Ingold-Prelog (CIP) rules stand as the official way to specify chirahty of molecular structures [35, 36] (see also Section 2.8), but can we measure the chirality of a chiral molecule. Can one say that one structure is more chiral than another. These questions are associated in a chemist s mind with some of the experimentally observed properties of chiral compounds. For example, the racemic mixture of one pail of specific enantiomers may be more clearly separated in a given chiral chromatographic system than the racemic mixture of another compound. Or, the difference in pharmacological properties for a particular pair of enantiomers may be greater than for another pair. Or, one chiral compound may rotate the plane of polarized light more than another. Several theoretical quantitative measures of chirality have been developed and have been reviewed elsewhere [37-40]. 

The currently used (R,S)-nomenclature of asymmetric C-atoms and similar tetracoordinate configurations is based upon the sequential order of the ligands derived from the CIP rules. If one orients an asymmetric C-atom in such a manner that the fourth ligand points backwards, the indices of the first three ligands of an (I )-configuration increase in a clockwise pattern, and counterclockwise for an (S)-configuration. 

In Figure 4.2 we have drawn how we can distinguish the two faces of an alkene, or rather the side of attack of a specific atom of the alkene. The arrow on the left approaches the lower carbon of the alkene and when looking from this viewpoint we count the weight of the three substituents the same way as in the CIP rules. We then see the order 1, 2, and 3 counter-clockwise, and we say that the arrow approaches the carbon atom from the si face. For simplicity we call this the si face of the alkene and in most cases this will do. If all four substituents at the alkene are different we can determine the re/si properties of both carbon atoms and these may be different This results in the nomenclature that an alkene may have a re,re and si,si face or re,si and si,re face. Thus, in the latter case one has to indicate to which atom the label is referring. For any enantiospecific, catalytic reaction (hydrogenation, hydroformylation, polymerisation) it is very convenient to use the re and si indicators in the discussion. 

For Ci bidentate ligand systems there may be exceptions to this explanation, which have been called memory effects [7], That is to say, the cyclohex-2-en-l-ylpalladium complex remembers whether it was formed from the R or the S isomer of the starting acetate Thus the R enantiomer is transformed preferably into the R product (neglecting changes in the atom counting in the CIP rules), and the same for S, because the reaction sequence involves two reversions of configuration. 

The concepts described in points and have not resulted in difficulties, however is not easy to understand. Its meaning, stated in other words, is that a rank established for an atom in a given sphere remains valid for the entire branch that originates from that atom. The problem was brought into focus by Cahn with example 4 (see Table 4), where he first transgressed the CIP rules, but later published an erratum8. This example is discussed here in a very detailed manner (Table 5). 

In the areas of coordination and metalorganic compounds the CIP system was adopted in part (Sequence Rules), but a variety of special conventions mainly concerning constitution and descriptor assignment rules for stereogenic centers with more than four ligands have emerged. An excellent review is available1, and here only those types of compounds relevant to this volume are discussed. 

By comparison with the known values of optical rotation the configuration at C-3 of the predominant enantiomer of the 3-phenylalkanoic acid was R in most cases (CIP rules dependent). Therefore, a bicyclic structure of the dilithio compound, in analogy to that proposed for the deprotonated 3-phenyl-2-propenyl ether21, which is alkylated in a metalloinversive reaction mode seems to be reasonable. 

The first step here is to draw formulae of both isomers of cromakalim and then to determine the absolute configuration of both compounds using the CIP rules. The two compounds are the 3S,4R isomer and the 3R,4S isomer, and are enantiomers. The INN for the pure 3S,4R enantiomer is levcromakalim. 

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