Right substituent choice

D. Rule number four the right substituent choice... 

The right substituent choice minimahzes the number of test compounds that have to be synthesized to insnre a significant space volume. This point represents a 3D extension of the Craig plot discnssed by Craig" and by Anstel. In this context, the decision tree proposed by Topliss allows a fast identification of the snbstitnents associated with the highest potency. Application examples of the Topliss scheme are discussed by Martin and Dnnn. ... 

A Rule 1 The minor modifications rule B Rule 2 The biological logic rule C Rule 3 The structural logic rule D Rule 4 The right substituent choice E Rule 5 The easy organic synthesis (EOS) rule... 

As the results show, the chirality of the a-alkoxy center, as well as the type of allyl metal employed, are the two most important determinants for the stereochemical outcome of the reaction. In other words, the 1,2-asymmetric induction combined with the right choice of the allyl organometallic overrides the influence of the chiral nitrogen substituent. 

From a chemist s point of view, the common feature of the many spiro-linked compounds synthesized so far is the central core of spirobifluorene (1), which is substituted with equal or different substituents in the 2,2 and 7,7 positions, and, in some cases, also in the 3 and 6 or in the 4 and 4 positions, as shown in Fig. 3. There currently exist several pathways to the synthesis of spiro-Unked functional materials, whereas the choice of the right pathway depends on the desired substitution pattern. Compounds, which are fully symmetrically substituted in all fom para positions, i.e., R1 = R2 = R3 = R4, are generally synthesized from spirobifluorene itself. This strategy is also appUed for spiro compoimds with a synunetrically sixfold substitution pattern in the 2, 2, 4, 4, 7, and 7 positions. In the case of the horizontally unsymmetrical compounds, in which Rl = R2 R3 = R4, a more complex strategy has to be applied. Vertically unsynunetrical spiro compounds, in which R1 = R3 R2 = R4, can be accessed by direct substitution of spirobifluorene provided that the first two groups entering in the 2 and 2 positions deactivate the 7 and 7 positions, so that a subsequent substitution in these positions can be controlled. 

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