Pseudoasymmetric

In most cases with more than two chiral centers, the number of isomers can be calculated from the formula 2", where n is the number of chiral centers, although in some cases the actual number is less than this, owing to meso forms.An interesting case is that of 2,3,4-pentanetriol (or any similar molecule). The middle carbon is not asymmetric when the 2- and 4-carbon atoms are both (/ ) [or both (5)] but is asymmetric when one of them is (/ ) and the other (5). Such a carbon is called a pseudoasymmetric carbon. In these cases, there are four isomers two meso forms and one dl pair. The student should satisfy himself or herself, remembering the rules... 

The two meso forms, although optically inactive differ in chemical properties. For example, on heating the meso form A, readily forms a lactone, whereas the meso form B does not. In such an example the central carbon atom is said to be pseudoasymmetric. But if one of the carboxyl groups is esterified so that the top and bottom parts of the molecule become structually different, then the central carbon atom becomes truly asymmetric and the molecule would have three true asymmetric atoms and it will exist in eight stereoisomeric forms. 

The remaining cases reclassified by Prolog and Helmchen are tetrahedral centers with four distinct ligands, of which two and only two are enantiomorphic ligands in diastereotopic positions (as in 16a, Fig. S). These centers were originally regarded as pseudoasymmetric (39), and had received descriptors that did not change on reflection. Therefore, no anomaly had to be corrected. When these centers were reclassified as chiral (5), the Sequence Rule was also modified ... 

A second problem that has repeatedly concerned us is the inability of the Sequence Rule to provide descriptors for some elements of stereoisomerism. When Cahn et al. (16) first encountered this problem with the all-cis and all-trans isomers of inositol, they attributed it to the fact that the symmetry has become so high that they have no asymmetric, nor even a pseudo-asymmetric atom. This interpretation, we believe, is incorrect. If the two ring ligands of any carbon atom of m-inositol were not heteromorphic, their exchange could not yield an isomer, as it clearly does. Each atom is a center of stereoisomerism with a pair of enantiomorphic ligands (Cg+g hi) and indistinguishable from the traditional pseudoasymmetric atom. The description of cu-inositol as all-5 could be accomplished by the same device that would allow one to specify the configurations of C(l) and C(4) of 4-methylcyclohexanol. 

A brief history of the varying interpretations of the term pseudoasymmetric has been given (1,3). Prelog and Helmchen (5) have not limited their idea to the pseudoasymmetric center, axis, or plane but have presented the closely related concept of a general pseudoasymmetry... 

Tertiary carbon atoms along the chain have been defined as asymmetric (22-25, 34-37), pseudoasymmetric (6, 10, 38-40), stereoisomeric centers (30, 31), and diasteric centers (41). The first two terms put the accent on chirality and are linked to the use of models of finite and infinite length, respectively the last two consider only phenomena of stereoisomerism. Note the relationship between these last definitions and Mislow s and Siegel s recent discussion (42), where the two concepts—stereoisomerism (or stereogenicity) and chirality—are clearly distinguished. The tertiary carbon atoms of vinyl polymers are always stereogenic whether they are chinotopic or achirotopic (42) depends on stmctural features and also on the type of model chosen (43). 

The terms stereocenter, chirotopic, and achirotopic will be used in this text in line with the most recent terminology. However, other terms are found in the older literature. C was previously referred to as a chiral or pseudochiral center. The term pseudochiral center is based on the same convention used to classify C as achirotopic instead of chirotopic. The terms asymmetric and pseudoasymmetric center are found in much older literature. 

There is a fundamental difference between a chirality center and a pseudoasymmetric center and that is that reflection and permutation of ligands have the same effect for the chirality center, but not for the pseudoasymmetric center. This is because, on reflection of the latter, the chirality senses of both the center, seen when the bonds are numbered, and each of the enantiomorphic ligands are reversed. Another way of stating the difference is that Re/Si and rejsi descriptors specify absolute and relative configuration, respectively. Pseudoasymmetric is a most unfortunate term, and in order to avoid it, the classical terms chirality center and pseudoasymmetric center would perhaps best be replaced by more neutral terms, such as stereogenic centers of type 1 and type 2, respectively, in order to emphasize the aspect of stereogenicity. 

In analogy to the case of the two-dimensional pseudoasymmetric center (see Section 1.1.2.2.) pseudoasymmetric stereogenic units are encountered when enantiomorphic ligands (F/F) are located in positions of the core (with residual ligands), that are reflection equivalent but not rotationally equivalent, i.e., in enantiotopic positions. Again, lowercase letter descriptors (r/s, pjm) are used in order to express invariance to reflection. The previous criticism concerning the term pseudoasymmetric (see Section 1.1.2.2.) also applies here and will be elaborated in Section 1.1.3.5. 

Obviously, permutation and reflection do not, in general, give identical results. Unfortunately, the important classical terms asymmetric atom (center) and pseudoasymmetric atom (center)... 

Initially, it might appear that the concept chirotopicity provides terms for replacing the inadequate chirality unit and "pseudoasymmetric" unit (see Section 1.1.3.3.) as in the simple models... 

X(ABCD) and X(FFCD) the centers X are clearly chirotopic and achirotopic, respectively (see Section 1.1.3.5.). However, this possibility is barred, as the permutation characteristics of these units are preserved in chiral models such as X(AFFG), with three chiral ligands. Here we have a pseudoasymmetric center and X is chirotopic. This observation emphasizes again the necessity to separate the concepts of stereogenicity and symmetry relationships. 

Sequence rule 5. i.e., R> S, covers pseudoasymmetric" units, requiring descriptors r and s. Note that the descriptors R and 5 refer to isolated ligands, i.e., the r,s descriptors are not... 

Mislow and Siegel11 criticized the CIP system, inter alia, by totally denying symmetry-adaptation of it. The above enumeration, however, should suffice to demonstrate that this disqualification is certainly not appropriate for stereogenic units of tpye 1. Their comments on "pseudoasymmetric centers 11 unfortunately use varying viewpoints and make erroneous assignments of descriptors. The point at issue, which is of fundamental significance, is best explained by the examples 1, 2, and ent-2, also used by these authors. 

Pseudoasymmetric (unit) - This term is today considered inappropriate, but a substitute has not emerged. The author proposes stereogenic unit of type 2 (see Section 1.1.3.5.). 

The addition criterion may similarly be applied to recognize diastereotopic faces. Methyl a-phenethyl ketone, 58 in Fig. 19 has a chiral center addition clearly gives rise to diastereomers (59a, 59b) the faces of the carbonyl carbon are diastereotopic and the C = 0 group is prochiral. This case is of importance in conjunction with Cram s rule 10). Compounds 60, 62 and 64 also display diastereotopic faces even though the products 61, 63 and 65 are not chiral 60, 62 and 64 have prostereogenic rather than prochiral faces. The C=0 group in 60 is propseudoasymmetric, since C(3) in 61 is a pseudoasymmetric center. a-Phenethyl methyl sulfide (66) displays diastereotopic sides of a molecular plane not due to a double bond 5,24> and may alternatively be considered a case of diastereotopic phantom ligands (unshared pairs on sulfur). This case does involve chirality and the sulfur atom is prochiral. 

Just as chiral centers can be labeled if or S not only in enantiomers but also in many diastereomers, so the designations pro-R and pro-S are not confined to enantiotopic ligands but may also be used for a number of diastereotopic ones (for exceptions, see below). Thus, for example, the labeling in Fig. 13 is such that HA (compounds 30, 32, 34, 36) or Me1 (compound 38) is the pro-R group the reader should verify this proposition. The same is true for compounds 46 and 5(5 in Fig. 18. Compounds 48, 50, 52 and 54 in Fig. 18 cannot be labeled in this manner since replacement of the diastereotopic ligands does not produce chiral products. In 54 (pro-pseudoasymmetric center) the substitution gives rise to a pseudoasymmetric center which, in the compound of the left is s, in the compound on the right r. Hence HA is called pro-r and HB pro-s 6>. 

S- Abbreviation for symmetric(al), as in i-triazine (1,3,5-triazine). Also an abbreviation for sec-, as in i-butyl. Both of these usages are obsolete the current use of s- is as a descriptor for pseudoasymmetric centres (see Chapter 7). 

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