Chiral organic compounds

Posner and coworkers have published a series of papers in which they described a successful application of the Michael reaction between a variety of carbanionic reagents and chiral cycloalkenone sulphoxides 557 to the synthesis of chiral organic compounds (for reviews see References 257, 649, 650). In several cases products of very high optical purity can be obtained. Subsequent removal of the sulphinyl group, serving as a chiral adjuvant, leads to optically active 3-substituted cycloalkenones 558 (equation 356 Table 27). 

Thus, a slight enantiomeric imbalance in compounds induced by CPL was correlated for the first time to an organic compound with very high ee by asymmetric autocatalysis with amplification of chirality. Moreover, various chiral organic compounds such as 1,1-binaphthyl,[2.2]paracyclophanes, and primary alka-nols due to deuterium substitution have been found to serve as chiral triggers in asymmetric autocatalysis. 

As described, a chiral organic compound with high ee is formed using chiral inorganic crystals in conjunction with asymmetric autocatalysis. 

In contrast, the use, in chromatography, of poly(trityl methacrylate) appears much more promising. Both the insoluble polymer and macroporous silica gel coated with a soluble polymer have been used. The latter system gives better results, especially with regard to elution time. The columns have proved quite efficient in resolution of a great variety of chiral organic compounds (365, 388). Other examples of usefiil chiral polymer supports are the substituted polyacrylamides (389). Earlier used adsorbents obtained by reacting optically active amines with polyacryloyl chloride have been superseded by new chiral phases prepared by direct polymerization of optically active acrylamides. 

In place of the above-mentioned chiral organic compounds, chiral inorganic substrates have been examined as chiral initiators. Quartz (Si02) exhibits both dextrorotatory (d) and levorotatory (Z) enantiomorphs that exist in nature. Quartz is considered as one of the origins of chirality of organic compounds186. 

Enantlomerically pure B-suhstituted carbonyl compounds serve as useful intermediates in the synthesis of many chiral organic compounds. The enantloselective synthesis of acyclic 0-substituted carboxylic acids has been reported by Meyers, Mukaiyama, and Koga. However, no effective, general method for the enantio-controlled preparation of P-substituted cycloalkanones was available prior to the investigations by the submitters. For example, poor enantloselectivity was observed in conjugate additions of organometallic... 

Evidently, many simple chiral organic compounds that act as catalysts can be covalently bound to polymer backbones. Polymer-anchored quinine catalyzes the asymmetric Michael addition of a jS-keto ester to methyl vinyl ketone, which proceeds in 22-42% optical yield (Scheme 13) (29). 

Certain chiral organic compounds create crystalline environments and act as enantio-controlling media (7) even though they do not function as true catalysts. Natta s asymmetric reaction of prochiral trans-1,3-pentadiene, which was included in the crystal lattice of chiral perhydro-triphenylene as a host compound, to form an optically active, isotactic polymer on 7-ray irradiation, is a classic example of such a chiral molecular lattice (Scheme 1) (2). Weak van der Waals forces cause a geometric arrangement of the diene monomer that favors one of the possible enantiomeric sequences. 

The synthesis of new chiral organic compounds and the improved synthesis of known substances will always be a major task for the professional chemist. When constructing target molecules with multiple chirality centers, a scientist must consider either total synthesis step by step or assembly from smaller chiral blocks as an alternative approach. 

Asymmetric Autocatalysis Triggered by Chiral Organic Compounds... 

Scheme 9 Asymmetric autocatalysis initiated with chiral organic compounds...

Chiral Organic Compound with Vary Lowes... 

We reasoned that chiral organic compounds with low ee induced by CPL can act as a chiral trigger in the enantioselective addition of z -Pr2Zn to pyrimidine-5-carbaldehyde, and that the subsequent asymmetric autocatalysis of pyrimidyl alkanol, formed in situ, amplifies its ee to produce highly enantioenriched pyrimidyl alkanol with an absolute configuration corresponding to that of the handedness of the CPL. 

For a typical chiral organic compound, such as 2-butanol, the circular birefringence, nL - wR, at A = 589 nm is of the order of 10-7. Even for a very high a = 40° mm-1 at A = 589 nm ( wL - nR 2 X 10 4), linear birefringence, which may arise from residual ordering/aggregation of polymer chains, could easily overwhelm the circular birefringence. 

Most chiral organic compounds have at least one asymmetric carbon atom. Some compounds are chiral because they have another asymmetric atom, such as phosphorus, sulfur, or nitrogen, serving as a chirality center. Some compounds are chiral even though they have no asymmetric atoms at all. In these types of compounds, special characteristics of the molecules shapes lend chirality to the structure. 

Ramamurthy and coworkers have utilized zeolites modified with chiral organic compounds [17,18]. Zeolites are crystalline aluminosilicates with open framework structures. In this approach, the zeolite is first loaded with a chiral inductor and the compound to be photolyzed is then added in a second, separate adsorption step. Asymmetric induction ensues as a result of the close proximity enforced between reactant and chiral inductor in the confined space of the zeolite supercage. The zeolite method has the disadvantage that the size of the substrate is limited by the pore size of the zeolite being used. Most of the work using the chirally modified zeolite approach was compared with the ionic chiral auxiliary method by Scheffer and coworkers. The enantiodifferentiations by the zeolites are usually low to moderate. 

Chemists who wish to prepare enantiomerically pure phosphines should consult the excellent review by Pietrusiewics and Zablocka,45 which gives examples of most of the P-chiral phosphines that have been made efficiently. In the last 10 years, a number of effective asymmetric syntheses of P-chiral phosphines have been developed. Prior to this, many of the chiral phosphines prepared were synthesized in racemic form and then resolved using stoichiometric amounts of a chiral organic compound or chiral palladium, platinum, or iron complexes. Although some interesting phosphines have been prepared by this method, they are not mentioned here as the experimental procedures are not in widespread use. 

This section is meant to give a short survey on the applications of chiral ferrocenes for the synthesis of (mostly chiral) organic compounds. Applications of phosphines will be treated very briefly, as they are the topic of a separate chapter of this book (Chapter 2). The same is true for the reaction of zinc alkyls with carbonyl compounds. 

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