Coordination chemistry enantioselective synthesis

Agbossou E., Carpentier J. E. Hapiot E., Suisse I., Mortreux A. The Aminophos-phine-Phosphinites and Related Ligands Synthesis, Coordination Chemistry and Enantioselective Catalysis Coord. Chem. Rev. 1998 I78-I80 1615-1645 Keywords stereoselective Diels-Alder reaction catalysts, aminophosphine-phosphinites, enantioselective catalysts... 

The chemistry of titanium has been reviewed in COMC (1982) and COMC (1995)40 41 as well as in Comprehensive Coordination Chemistry II. 2 Since then, several contributions have covered the coordination chemistry of cyclopenta-dienyltitanium carboxylates and related complexes,43 new titanium imido chemistry,44 the use of titanium(iv) chloride45 and isopropoxide46 in stereoselective synthesis, the preparation and synthetic applications of l, -dicarba-nionic titanium intermediates47 and organotitanium complexes,48 49 and titanium-catalyzed enantioselective... 

Solvents effect equilibria and rates of reactions, which is not only important in synthesis and catalysis, but in other processes such as the rate of electron transfer. Thus far, the effect of chiral solvents on chiral recognition and enantioselective catalysis has not proven effective, but without further experiments, it is too early to draw any firm conclusions.10 There are many theories and rules relating to solvent effects on reactions, the majority developed with organic processes in mind, and discussions of these are not relevant here. Rather, the importance of solvent selection relevant to coordination chemistry will be illustrated with some key examples. 

In organic and organometallic chemistry, asymmetric catalysts play an important role in enantioselective synthesis, and the majority of these are mononuclear organometallic compounds. It was for their work on asymmetric catalysis that W. S. Knowles, R. Noyori and K. B. Sharpless won the Nobel Prize for Chemistry in 2001, " and hence the study of chirality for this class of compounds is of the utmost importance. For this reason, following on from Chapter 2, which lays the necessary groundwork in organometallic and coordination chemistry, in Chapter 3 we will develop the study of the chemistry of chiral mononuclear organometallic complexes and asymmetric catalysis in brief. 

The demonstration of the optical activity of octahedral complexes was important in confirming Alfred Werner s intuitive ideas about coordination chemistry. Early work involved the resolution of complexes characterized by optical rotations. Modem instmments for optical rotatory dispersion were developed first, but circular dichroism (CD) spectra proved to be more useful. CD has been a powerful tool for detailed studies of the stereochemistry of octahedral complexes. Contributions to rotational strength of chelate ring conformational, configurational, and vicinal contributions are additive. Chiral metal complexes are now used in enantioselective synthesis of chiral pharmaceuticals. 

The Aminophosphine-Phosphinites and Related Ligands Synthesis, Coordination Chemistry and Enantioselective Catalysis. 

A significant contribution in the area of low-coordinate boron chemistry was realized by Corey with the synthesis of chiral tri-coordinate and cationic oxaborolidine complexes such as (4), for use in asymmetric catalysis. These compounds can be obtained by reaction of the desired chiral aminophenol with BBrs, and they are highly effective catalysts for enantioselective Diels-Alder reactions. Smith also reported the generation of the tri-coordinate boron cation HC(CMeNAr)2 BMe+, obtained by a Me abstraction reaction of HC(CMeNAr)2 BMe2 by B(C6F5)3. This boron cation appears to be much less Lewis acidic than its A1 counterpart. 

A classical method for the preparation of enantiopure compounds is the resolution of racemate. However, it is much more effective to use the selective synthesis of the desired enantiopure substance via enantioselective approach. Stereoselective methods of synthesis have been widely developed in organic chemistry. The method of asymmetric synthesis has been known since the nineteenth century and asymmetric catalysis has witnessed an enormous amount of development in recent decades as shown in Chapter 3. In contrast, the asymmetric synthesis of coordination compounds has only recently become a subject of systematic investigation. This is no doubt related to the fact that the chirality of coordination compounds is a much more complex phenomenon than that of organic compounds, because of higher coordination and the multitude of possible central atoms. Furthermore, while in organic chemistry the chiral tetrahedral carbon centres can be prepared without racemization, in contrast T-4 metal centres are very often labile. In fact it is even difficult to prepare compounds with a metal centre coordinated to four different monodentate ligands, and thus the possibility of obtaining one enantiomer is excluded in most cases. 

The combination of a lipase and Shvo s catalyst has also been applied to the DKR of a- and jS-hydroxyphosphonates. Hydroxyphosphonates are an important class of substrates, with applications in medicinal chemistry (haptens of catalytic antibodies, phosphonic acid based antibiotics), biochemistry (enzyme inhibitors) and organic synthesis. Under typical conditions, Backvall s group has shown that the DKR of several dimethyl- and diethyl-a-hydr-oxyphosphonates proceeded with excellent enantioselectivities and moderate to good yields (Scheme 4.18). This was attributed to the coordination of the phosphonate moiety to the ruthenium catalyst at a low alcohol concentration. This DKR procedure was also applied to the de-racemisation of diethyl jS-hydroxyphosphonates. However, in contrast to the DKR results on the... 

Besides these organocatalytic methods, enantioselective Biginelli reactions can be induced by means of chiral Lewis acids. Indeed, the first synthesis of a highly enantioenriched dihydropyrimidine (compound 46) via Biginelli chemistry was developed by Zhu and coworkers in 2005 [46] and was based on the use of the chiral ytterbium species 47 as a Lewis acid catalyst. This reaction gave very good chemical yields and enantioselectivities and showed excellent functional group tolerance. In the proposed transition state, coordination of the catalyst with intermediate 48 leads... 

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