Synthesis symmetrical analogs

Chiral Amines with C2 Symmetry, trans-2,5-Dimethylpyrrolidine (1) was the first chiral amine possessing C2 symmetry used as a chiral auxiliary in asymmetric synthesis. Since that time a number of related systems have been developed including the title compound (2) and (4). These amines were developed as C2-symmetric analogs to the commercially available prolinol derivative (5). While proline-derived chiral auxiliaries have been widely used in asymmetric synthesis, the C2-symmetric chiral auxiliaries often give enhanced stereoselectivity when compared directly to the prolinol derivatives. Unfortunately the preparation of the C2-symmetric compounds is more tedious and, at the time of writing, none are commercially available. For example, the standard route to chiral pyrrolidines (2) and (3) involves the resolution of tranf-N-benzylpyrrolidine-2,5-dicarboxylic acid, although other preparations have been... 

Marsella and coworkers exploited perfluorophenyl-phenyl quadrupole interactions to template the synthesis of a thiophene-containing cyclophane [44]. As shown in Scheme 6.14, when the oligomeric precursors 98-101 were treated with Sonogashira cross-coupling conditions, the mixed perfluorophenyl-phenyl cyclophane 102 was reproducibly achieved in greater yield than either of the symmetrical analogs 103 and 104. Other mixed macrocyclic derivatives were also prepared as part of this study, and their findings with these model systems supported... 

This phenol synthesis complements the analogous reaction (see below) from arylthallium ditrifluoroacetates (147). Although yields are only moderate, the procedure represents a viable conversion of aryl Grignard reagents to phenols. It is a practical method, however, only when the diarylthallium trifluoroacetate precursor is formed via the Grignard route the alternative synthesis via symmetrization of arylthallium ditrifluoroacetates is obviously circuitous, since the latter compounds may be converted directly to phenols. 

In the outstandingly successful Cl Reactive Black 5, two such precursor-bearing units are used in the synthesis of this near-symmetrical bifunctional structure (7.36). Following this precedent, competing bifunctional dyes of analogous structure were designed with two phenylene-l,3-diamine-4-sulphonate groupings to accommodate the reactive systems... 

The symmetrical thioindigo dyes have the structure (355), where R = Cl, Br, Me, NH2, OMe, OEt or SEt located at the 4-, 5-, 6- or 7-position of the benzo[6 jthiophene parent compound, or combinations of two or three of these substituents. The original Friedlander synthesis involved mild oxidation of a 3-hydroxybenzo[6 jthiophene, but numerous methods, many patented, have been used. The 2,3 -bithioindigos, also known as thioindirubins (356), by analogy with the indigo isomer, indirubin, are also dyes of some interest. 

The synthetic protocols used for the preparation of oligonucleotides on supports can also be used to prepare oligomers from diols other than nucleosides. Symmetric or unsymmetric diols, such as N-acylated 4-hydroxyprolinol [268] or cyclopentane-derived diols (carbocyclic deoxyribose analogs [269]), can be selectively mono-trity-lated and then converted into a phosphoramidite that is suitable for the solid-phase synthesis of oligophosphates. An illustrative synthesis of protected //-phosphonates from diols, as well as their conversion on CPG into oligomeric phosphoramidates, are outlined in Figure 16.28. 

An alternate synthesis is outlined in Scheme 2.1 2 Diisopropyl dichloromethylboronate (6) is readily prepared by reacting triisopropyl borate with dichloromethyllithium prepared in situ. 20 Transesterification with a suitable C2 symmetric diol gives an ester 7 that can be treated with an alkylmagnesium bromide to yield chloride 8 and then, after transesterification with pinanediol (see Section 15.1.7.2) a product 9 which is analogous to 3. 

The synthesis of both symmetrically and unsymmetrically substituted organopolysilanes is achieved in analogous fashion to that of permethylated polysilanes. Some examples are given below. 

The progression from desymmetrisation (Scheme 2) to deracemisation (Schemes 3-6) leads to a useful general insight. The desymmetrisation of <7-symmetric difunctional compounds (31 32, Scheme 7) is a common approach to asymmetric synthesis [14], and there may be various circumstances where the regeneration of functional symmetry, but with stereoinversion, is also possible (32 33). If 31 is now allowed to mutate into the asymmetrical 34, present as a racemate, it is likely that the desymmetrising reaction will yield 35 -i- 36, converging on 37 after the final step. Any desymmetrisation of cr-sym-metric (e.g. meso) diols may thus be extended, potentially, to deracemisation, and other substrates may lend themselves to analogous sequences. 

---