Trans-directing ability

The trans effect is useful in synthesis. For example, different isomers are formed in the reactions below by the greater trans directing ability of Cl- compared, with NH3 ... 

Moreover, selective iodolactonization to furnish 3,4,5-trisubstituted lactones, when a methyl substituent at C-2 and an oxygenated function at C-3 are present in the unsaturated amide substrate, has been studied. Thus,. > 7-3-hydroxy-iV,./V-2-trimethyl-4-pentenamide (, > -25, R = H), has been lactonized with a selectivity of 98 % to give the 3,4- ra s-4,5-rt.y-4-hydroxy-5-iodomethyl-3-methyl-y-lactone 26A (R = H), due to the 1,3-trans directing ability of the 3-methyl substituent and the 1,2-cis directing ability of the 4-hydroxy group. 

On the other hand, when fl t -3-hydroxy-/V,/V-2-trimethyl-4-pentenamide (anti-25, R = H) is cyclized under the same conditions, a 20 80 mixture of the 4,5-trans- and 4,5-m-lactones is obtained in 88% yield. This result shows the prevalence of the 1,2-cis directing ability of the jS-hydroxy group over the 1,3-trans directing ability of the a-methyl substituent. 

The trans directing ability of MeCN at Pt(II) has been compared with its trans influence, by examining replacement reactions of [PtCl3(NCMe)] by amines for the former, and the X-ray crystal structure for the latter. The directing influence (dynamic trans effect) is high while the bond-weakening trans influence is low. 

Substitution reactions in square planar complexes take place via associative mechanisms. In the kinetic trans effect, a series can be constructed in which species are put in order of their ability to labilize ligands trans to themselves. Using this series, high-purity square planar isomers can be readily synthesized. The trans-directing ability of a ligand is also directly related to its polarizability. 

An approximate order of Hgands according to their trans-directing ability is... 

The order of trans-directing abilities of NH3 < Cl < N02 permits the selective synthesis of isomers of the type [Ma2bc] fixim [Ma4] type of complexes. Consider the preparation of [Pt Cl2(N02)(NH3)] from [PtCLj] . If the ammonia Ugand is introduced in the first step, it can occupy any of the four positions replacing a chloro Ugand. In the second step, the incoming N02 is offered a position trans with respect to chlorine... 

According to this theory, the trans-directing ability of Hgands with greater polarizabhity is more. 

In the absence of substituents with directive abilities, the peroxy acid usually approaches the alkene from the least-hindered face <86JOC793>, and such reactions are diastereoselective. Simple alkenes are relatively insensitive to steric effects cis-, trans- and 1,1-disubstituted alkenes react at nearly the same rate Facial selectivity with simple alkenes is difficult to achieve however, progress has been made in this area <84JA1170>. By using bulky peroxy acids, cis/trans selectivity has been achieved to a considerable extent. 

Experimental rates of substitution are affected by both the ground state traHx-influence and the kinetic trans-tStcl, and rationalizing the sequence above in terms of individual factors is difficult. There is no close connection between the relative magnitudes of the traH -influence and trans-eSect. However, the 7r-bonding scheme in Figure 26.5 does help to explain the very strong fra/rx-directing abilities of CO, [CN]- and ethene. 

After ligands are classified with respect to their /ra s-directing ability, the information can be used to synthesize specific desired compounds. The three isomers of [Pt(N02)Cl(CH3NH2)NH3] can be prepared by the reactions outlined in Figure 4.1. The success of these syntheses depends on the trans effect order NO2 > Cr > NH3 CH3NH2. However, this information on the trans effect will not of itself permit one to propose such a reaction sequence. Another consideration is the stability of the various platinum-ligand bonds. The trans effect will explain the synthetic results in steps (a), (c), and (/) but the relative ease of replacement of chloride coordinated to platinum(n) accounts for steps (b), (d), and (e). 

In an elegant series of experiments Miele et al. (45) have shown that VEGF mRNA induction by insulin and IGF-I in NIH3T3 fibroblasts transfected with either human IR or IGF-IR occurred by preferential use of the PI3K pathway in case of insulin/IR or the MAPK pathway in case of IGF-I/IGF-IR. Although the authors depicted no direct link to HIF-1, one can speculate that two different mechanisms led to the elevated VEGF mRNA levels. In the first case the mechanism was, in all likelihood, an increased HIF-la protein amount rather than enhanced trans-activation ability, whereas in the second case it was an enhanced /ran -activation ability rather than an elevated HIF-la amount. However, in vivo phosphorylated and dephosphorylated HIF-la seems to have different functions since phosphorylated HIF-la is the major form that binds to HIF-ljS and activates transcription, whereas the dephosphorylated form binds to and stabilizes p53, which in turn initiates cell cycle arrest and apoptosis (46). 

A second isomer of [lOJannulene (the cis trans cis cis trans stereoisomer) can have bond angles close to 120° but is destabilized by a close contact between two hydro gens directed toward the interior of the ring To minimize the van der Waals strain between these hydrogens the nng adopts a nonplanar geometry which limits its ability to be stabilized by tt electron delocalization It too has been prepared and is not very stable Similarly the next higher (4n + 2) system [14]annulene is also somewhat desta bilized by van der Waals strain and is nonplanar... 

Figure 10.12 Response elements for heterodimers of the nuclear receptor for ds-retinoic acid (RXR) with the receptors for vitamin D (VDR), thyroid hormone (TR) and trans-retinoic acid (RAR). The half-sites of these response elements have identical nucleotide sequences and are organized as direct repeats. They differ in the number of base pairs in the spacer region between the half-sites. This difference forms the basis for the ability of the heterodimers to discriminate between the different response elements.

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