Chiral annelation

In the aromatic-ring-annelated oxepin series the resonance effect is clearly the major influence dominating other factors (e.g. temperature, solvent, etc.) which affect the oxepin-arene oxide equilibrium. It is however very difficult to exclude the presence of a minor (spectroscopically undetectable) contribution from either tautomer at equilibrium. This problem has been investigated by the synthesis of chiral arene oxides from polycyclic aromatic hydrocarbons (PAHs). The presence of oxepin (26) in equilibrium with naphthalene 1,2-oxide has been excluded by the synthesis of the optically active arene oxide which showed no evidence of racemization in solution at ambient temperature via the achiral oxepin (26) <79JCS(Pl)2437>. 

H. Hashimoto, K. Furuichi, and T. Miwa, Cyclopentane annelated pyranosides A new approach to chiral iridoid synthesis, J. Chem. Soc. Chem. Commun. p. 1002 (1987). 

Amplification. See Chirality amplification Anhydrides, ring opening, 331 Anionic polymerization methyl sorbate, 174 trityl acrylate, 181 Annelation, Robinson method, 336 Antibiotics, 8, 44, 80 Antibodies, 12... 

Polarimetry, circular dichroism (CD) and optical rotatory dispersion (ORD) are the most important tools for the study of properties arising from optical activity. Although many chiral thiophenes have been prepared, there is no secure basis for a systematic discussion of the special effects of thiophene or annelated thiophene rings. For the purpose now at hand it is more expedient to discuss three different areas in which thiophene containing molecules and the related chiroptical techniques are central features. 

In summary, the SMS reaction is a truly efficient process, possessing a broad scope and applicable to a number of carbonyls, allylsilanes, alcohols (silyl ethers) or amines. Its usefulness has been validated in several total syntheses and demonstrated by the preparation of chiral homoallylic alcohols. During the development of the SMS reaction, Melkafia and Marko [48] realized that the homoallylic alcohol (ether), if connected to an allylsilane, would form novel annelating agents that would lead to tetrahydropyran derivatives via condensation with carbonyl compounds. This reaction was called IMSC for intramolecular Sakurai cydization and will be discussed in the next section. 

This novel annelation not only provides a route to chiral lactones, but was applied to a synthesis of a diol (8) from the acetal 7 as a precursor to (- )-lardolure (9). 

The indium trichloride-catalyzed Mukaiyama aldol reaction of 3-aminoketoesters with various silylenolethers gave under solvent-free conditions 1,3-amino alcohols with high stereoselectivity [36], Several Robinson annelation reactions have been carried out enantio-selectively using (S)-proline as a chiral catalyst [37]. Remarkably, the enantioselectivity was distinctly higher in the absence of solvent than in DMSO. 

This chapter addresses synthetic aspects of molecules with highly annelated chiral JT-conjugated systems, with the focus on helicene-type oligomers [20], In addition to synthesis, configurational stability (barriers for racemization) and selected chiroptical properties of such molecules will be discussed. 

Synthetic Approaches to Highly Annelated Chiral n-Conjugated Systems... 

For nonphotochemical syntheses, there are three major approaches (1) annela-tion of racemic intermediate leading to racemic [njhelicene, followed by resolution, (2) annelation of nonracemic intermediate giving nonracemic [njhelicene and (3) asymmetric synthesis, i.e. annelation of racemic intermediate in the presence of chiral reagent, catalyst or auxiliary. 

Annelations via Friedel-Crafts acylation were applied to racemic syntheses of [njhelicenes with n up to 6. The 12-step synthesis of [6]helicene (1) by Newman and Lednicer employed stepwise diannelation, followed by oxidative aromatiza-tion and then resolution with the complex of a chiral n-acceptor, a-2,4,5,7-tetrani-tro-9-fhiorohdeneaminooxypropionic acid (TAPA) and 1 [25]. The one-step diannelation was ubiquitously applied to syntheses of triarylamine [4]helicenes,... 

Annelation of nonracemic intermediate giving nonracemic [njhelicene Several methods for the transfer of center or axial chirality into helical chirality have been described. In many cases, practically complete transfer of enantiomeric excess was observed. 

An interesting example of the transfer of center chirality to helicity is the work by Ogawa et al., based on an asymmetric aromatic oxy-Cope rearrangement to provide nonracemic [5]helicenes (Fig. 15.8) [75]. The starting material with center chirality, bicyclo[2,2,2]ketone (-)-21 (>98% ee), was obtained by enzymatic resolution. In the annelation step, the phenanthrene derivative was subjected to aromatic oxy-Cope rearrangement, to afford a pentacyclic product in 47 % yield. The corresponding [5]helicene 22 was obtained in 7 % overall yield (> 98 % ee) after six steps. 

Fig. 15.11 Synthesis of highly functionalized enantiopure [7]thiahelicenes via kinetic resolution of axially chiral diketones and McMurry annelation.

Double and triple helicenes are Jt-conjugated molecules, which consist of two or three annelated helicene-like subunits. Such structures may also be considered as examples of chiral polycyclic aromatic hydrocarbons (PAHs). 

The achiral network of tetraphenylenes served as an inspiration for the design of a it-conjugated double helix. Double helical polymers, in which two polyphenylene helices are intertwined or tetraphenylenes are sequentially annelated, were recognized as the chiral building block of the network (Fig. 15.24) [107]. 

To date, the stepwise, kinetically controlled, classical synthesis is the most effective approach to highly annelated chiral Jt-systems. With significant improvements in asymmetric annelation methodologies, multi-step syntheses are likely to remain the main tool in the exploration of novel chiral structures. However, the development of novel synthetic methods will be essential for the preparation of polymers with extended helical-type, ladder-type connectivity of the Jt-systems. Important criteria are to minimize the density of defects in the ladder connectivity and to provide conjugation pathways circumventing at least some of the defects. 

Absolute Configuration in Two Molecules with Chiral Axes by Vibrational Circular Dichroism A C2-symmetric Annelated Heptafhiophene and a D2-symmetric Dimer of 1,T-Binaphfhyl, J. Phys. Chem. A 2003, 107, 7692-7696. 

Annellation of two benzene rings increases the barrier for the racemization process considerably and the -NMR-spectrum of (45) shows the expected splitting at room temperature120). Coalescence of the AA BB system for the CH2—CH2 moiety occurs at 128 °C (60 MHz) which corresponds to AG = 19.7 kcal/mole118,185>. By chromatography of (45) on a chiral phase (TAPA on silica gel) at —28 °C a partial separation of the enantiomers was achieved. 

Fig. 9. The first topologically chiral K5 molecule the centrally annelated polyquinane 53 and its K5 subgraph (54)...

A semipinacol rearrangement in tandem with a cyclization has been shown to be a powerful method for the construction of carbocyclic rings. Here the cyclization is initiated by an acetal function and terminated by a semipinacol rearrangement (Scheme 25). In some cases, the cyclization has been found to be stereospecific at the acetal center (equation 48), and up to four chiral centers can be generated in a single step (equation 49). Highly substituted tetrahydrofurans are obtained from cyclic acetals (Scheme 26), and stereoselective tetrahydrofuran annelations are possible using bicyclic acetals (Scheme 27). ... 

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