Ligand exploration

Figure 7. CIP relative priority numbers by ligand exploration...

Series of potential receptor ligands explored as the experimental variable... 

Scheme 19.8 Classical ligand exploration versus site-directed mutagenesis (SDM) exploration of structure-activity relationships (SAR). In the classical approach, various ligands are presented to the same receptor or active site of interest. In SDM, one or more ligands of merit are held constant and used as standards whereas various mutated forms of the receptor or active site are presented for interaction. Both approaches can produce useful SAR data and when used simultaneously, they can be highly complimentary.

Other typically organometallic ligands explored in this area were cyclopentadienyls, carboranes, and bridging hydrides [27-29]. AU these ligands allowed the synthesis in aqueous medium of Re and Tc tricarbonyl complexes (Fig. 44.4). 

The majority of U(V1) coordination chemistry has been explored with the trans-ddo s.o uranyl cation, UO " 2- The simplest complexes are ammonia adducts, of importance because of the ease of their synthesis and their versatihty as starting materials for other complexes. In addition to ammonia, many of the ligand types mentioned ia the iatroduction have been complexed with U(V1) and usually have coordination numbers of either 6 or 8. As a result of these coordination environments a majority of the complexes have an octahedral or hexagonal bipyramidal coordination environment. Examples iuclude U02X2L (X = hahde, OR, NO3, RCO2, L = NH3, primary, secondary, and tertiary amines, py n = 2-4), U02(N03)2L (L = en, diamiaobenzene n = 1, 2). The use of thiocyanates has lead to the isolation of typically 6 or 8 coordinate neutral and anionic species, ie, [U02(NCS)J j)/H20 (x = 2-5). 

From a historical perspective it is interesting to note that the Nozaki experiment was, in fact, a mechanistic probe to establish the intermediacy of a copper carbe-noid complex rather than an attempt to make enantiopure compounds for synthetic purposes. To achieve synthetically useful selectivities would require an extensive exploration of metals, ligands and reaction conditions along with a deeper understanding of the reaction mechanism. Modern methods for asymmetric cyclopropanation now encompass the use of countless metal complexes [2], but for the most part, the importance of diazoacetates as the carbenoid precursors still dominates the design of new catalytic systems. Highly effective catalysts developed in... 

The phosphine and arsine complexes of gold(I) have been intensively studied since the early 1970s. The possibilities of coordination numbers between 2 and 4 have been explored, though the use of bulky ligands is less essential than with the isoelectronic M(PR3)2 (M = Pd, Pt) compounds and the coordination numbers depend on both steric and electronic factors [71]. 

The surprising stability of N-heterocyclic carbenes was of interest to organometallic chemists who started to explore the metal complexes of these new ligands. The first examples of this class had been synthesized as early as 1968 by Wanzlick [9] and Ofele [10], only 4 years after the first Fischer-type carbene complex was synthesized [2,3] and 6 years before the first report of a Schrock-type carbene complex [11]. Once the N-heterocyclic ligands are attached to a metal they show a completely different reaction pattern compared to the electrophilic Fischer- and nucleophilic Schrock-type carbene complexes. 

An interesting parallel was found while the microwave-enhanced Heck reaction was explored on the C-3 position of the pyrazinone system [29]. The additional problem here was caused by the capability of the alkene to undergo Diels-Alder reaction with the 2-azadiene system of the pyrazinone. An interesting competition between the Heck reaction and the Diels-Alder reaction has been noticed, while the outcome solely depended on the substrates and the catalyst system. Microwave irradiation of a mixture of pyrazinone (Re = H), ethyl acrylate (Y = COOEt) and Pd(dppf)Cl2 resulted in the formation of a mixture of the starting material together with the cycloaddition product in a 3 1 ratio (Scheme 15). On the contrary, when Pd(OAc)2 was used in combination with the bulky phosphine ligand 2-(di-t-butylphosphino)biphenyl [41-44], the Heck reaction product was obtained as the sole product. When a mixture of the pyrazinone (Re = Ar) with ethyl acrylate or styrene and Pd(dppf)Cl2 was irradiated at 150 °C for 15 min, both catalytic systems favored the Heck reaction product with no trace of Diels-Alder adduct. 

Little progress has been made in the field of Group 15 metal amidinate and guanidinate derivatives. Only very recently some exciting results have been reported which demonstrate that this area may hold some real surprises and merits further exploration. It was found that amidinato ligands are capable to stabilize novel amidodiarsenes. Reduction of the four-membered ring As(III)... 

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