Facioselectivity

In organic, organometallic and biochemical reactions involving paired molecular (stereotopic) faces, one is confronted with two fundamental types of selectivity - facioselectivity and vectoselectivity. Facioselectivity characterizes the preferential reaction at molecular faces, and will be discussed in this chapter. Vectoselectivity refers to the relative alignment of reactants, and will be covered in the following chapter. 

In order to discuss facioselectivity concisely, cate needs to classify molecular faces (half-spaces). - In 1975, we categorized time-resolved/time-averaged planar stereotopic molecular faces into homotopic, enantiotopic, and diastereotopic classes.  

Stereotopicity and chirotopicity are deemed independent attributes of molecular sites - be it ligands, bonds, molecular faces or molecular segments. The former attribute is defined by a specific topic relationship between two given sites, whereas the latter attribute describes the chirality/achirahty of the molecular field. Indeed, two molecular sites are, with respect to one another, either stereotopic or nonstereotopic, irrespective of the achirality/chirality of the molecule in which they are situated. Conversely, a molecular site is either achirotopic or chirotopic, regardless of any stereotopic or nonstereotopic relationship(s) it may bear with respect to another (or other) intramolecular site(s). 

Homotopic faces are present in molecules 1-33. Achirohomotopic faces H/H are found in achiral molecules of subclasses hi (1,2), h2 (3,4), hs (5-13), whereas chirohomotopic faces H /H are present in chiral molecules belonging to subclasses h4 (14,15), hs (16,17), and h6 (18-33). Enantiotopic faces (E, 3) are exemplified by molecules 34-48 all of which are achiral no enantiotopic faces can exist in chiral molecules. Diastereotopic faces are found in molecules 49-70. Achirodiastereotopic faces D/F are observed in achiral molecules of subclasses di (49), d2 (50-52), da (53-61) while chirodiastereotopic faces D, F are present in chiral molecules of subclass d4 (62-70). 

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The preceding discussion was intended for two-component systems. A wide variety of chemical transformations do yield 3multicomponent systems, we will first extend the concept of selectivity to encompass situselectivity (Chapter 11), facioselectivity (Chapter 12), and vectoselectivity (Chapter 13). The specification of the various compositions of 2-, 3-, 4-component mixtures was given previously in Addendum A, Volume 1 (p. 143). 

These reactions bring out important and interesting consequences of the HED classification in the context of facioselectivity and difacioselectivity. Other consequences relating to stereoselectivity, stereospecificity, rotativity, stereotopoprocesses, and chirotopoprocesses, will be given in Volume 3, Chapters 17 and 18. Figure 12.5 represents the 45 quartets that emerge from our analyses. 

Table 12.2 lists the quartet number (q number), quartet component designation, and quartet composition of each of the 45 quartets. The quartets are subclassified into three categories -facioaselective, faciononselective and facioselective vide infra). 

For the example above, facioselectivity would be given by either Equation 12.1a (as a difference) or Equation 12.1b (as a ratio) ... 

Facioselectivity characterizes the preferential reaction at molecular face 1 (top) as opposed to reaction at paired face 2 (bottom). A reaction is said to he facioaselective if (a) every pathway (transition state) involved in the reaction at face 1 has an isoenergetic coimterpart a t face 2, and (b) both transition states of every isoenergetic pair are homomorphic. Quartets ql,q2 represent facioaselective transformations. Operationally, in an facioaselective transformation, the product(s) obtained from face 1 will be exactly identical (in structure and relative amounts) with that(those) obtained from face 2. 

Figure 12.7 below portrays all types of facioaselectivity, faciononselectivity and facioselectivity and the pertinent quartets. 

The quantitative expressions for facioselectivity for the three subclasses are as follows ... 

We now examine, in detail, aspects of facioselectivity at the eleven fundamental paired molecular faces - hi-he, e, and di-dr. These results are summarized in Table 12.3. 

Reactions of enantiotopic faces "e" are either afacioselective (ql) or nonfacioselective with achiral reagents (ql0,qll,ql2,ql5,ql6,ql7,ql8), but stereofacioselective (enantiofacioselective) with chiral reagents (q23,q24,q27,q37,q38,q41). With only enantio-facioselectivity at work, and no role for vectoselectivity - e.g. with C2-symmetric reagents - one would expect two chiral diastereomers (q23). With non-C2-symmetric reagents, vectoselectivity would come into play, and more complex mixtures may result (vide infra). Here, enantiofacioselectivity refers to the face type in the reactant substrate. 

Reactions of di-d4 are not always facioselective (diastereofacioselective) they can also be afacioselective or nonfacioselective as noted below. 

Table 12.3. Facioselectivity in Conjunctive Processes Involving Achiral and Chiral Reagents...

Figure 12.9. Examples of Facioaselectivity, Faciononselectivity and Facioselectivity at Enantiotopic Faces...

Figure 12.12. Facioselectivities of Ma and Mg in Face-Face Conjunctive Processes...

Facioselectivity at the two faces of Mg - moving front to back - is defined by Facioselectivity of Mg (reagent)... 

The octets can be grouped into six modes, based on facioselectivity of Ma and facioselectivity of Mg. This is given in Table 12.4 below. ... 

Enantiotopic faces e are facioaselective towards hi-he, faciononselective towards hi-he, e and di-d3, and, facioselective towards d4. 

In the case of diastereotopic faces, one finds that di is facioaselective towards hi-he, faciononselective towards hi-he and e, and, facioselective towards di-d4. In contradistinction, d2 and da are facioaselective towards hi and h4, faciononselective towards hi-he and e, and, facioselective towards di-d4. Finally, d4 is facioaselective towards hi and h4, faciononselective towards hi-he, and, facioselective towards e and di-d4. 

To clarify selectivity at faces of planar molecular fragments, or facioselectivity, we presented a complete classification of all eleven types of stereotopic molecular faces. W e defined the different modes of facioselectivity viz. facioaselectivity, faciononselectivity and stereofacioselectivity at each type of molecular face. We also discussed difacioselectivity for conjunctive processes involving the interactions of two molecular faces. 

Facioaselectivity Faciononselectivity Facioselectivity Facioaselectivity Faciononselectivity Facioselectivity... 

The reaction at a paired set of molecular faces, in principle, may proceed through four pathways that lead to a quartet of conjimctive states m, mi., m,-. This was shown in the discussion on facioselectivity (Chapter 12). 

The joint consideration of stereofacioselectivity and vectoselectivity for the 11 types of stereofaces (paired faces) leads to 12 facioselectivity-vectoselectivity modes - Aa, An, Na, Nn,... 

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