Bifunctional Systems

Fig. 23. Representative protecting groups for phenolic and carboxylic acid-based systems, (a) The polymer-based protecting groups are fisted in order of increasing activation energy for acid-catalyzed deprotection, (b) Acid-labile monomeric dissolution inhibitors, a bifunctional system based on protected bisphenol A. (c) Another system that combines the function of dissolution inhibitor and PAG in a single unit.

Bifunctional systems In the case of bifunctional systems (or molecules) only two alternatives are possible the bifunctional relationships are either "consonant" or "dissonant" (apart from molecules or systems with functional groups of type A to which we have referred to as "assonant"). In the first case, the synthetic problem will have been solved, in principle, in applying the "heuristic principle" HP-2 that is to say, the molecule will be disconnected according to a retro-Claisen, a retro-aldol or a retro-Mannich condensation, or a retro-Michael addition, proceeding if necessary by a prior adjustment of the heteroatom oxidation level (FGI). 

Simple reactivity inversion" implies using an umpoled synthon whose origin has, in principle, nothing in common with the synthon with "unnatural" polarity. An example of this type of reactivity inversion is found in one of the possible synthesis of cw-jasmone (3) in which the nitroethane (4) is used as an equivalent of an "acetyl anion" and reacts with an a,P-unsaturated ketone to give the corresponding 1,4-bifunctional system which can then be transformed by a Nef-type reaction into the dissonant 1,4-dicarbonyl system [5]. An intramolecular aldol condensation finally affords the target molecule (Scheme 5.3). 

Strategies based on functional groups, either mono- (IFG) or bifunctional systems (2FG). 

An interesting bifunctional system with a combination of In(OTf)3 and benzoyl-quinine 65 was developed in p-lactam formation reaction from ketenes and an imino ester by Lectka [Eq. (13.40)]. High diastrereo- and enantioselectivity as well as high chemical yield were produced with the bifunctional catalysis. In the absence of the Lewis acid, polymerization of the acid chloride and imino ester occurred, and product yield was moderate. It was proposed that quinine activates ketenes (generated from acyl chloride in the presence of proton sponge) as a nucleophile to generate an enolate, while indium activates the imino ester, which favors the desired addition reaction (66) ... 

The coupling of ketenes and imines has been reported to be catalyzed by a bifunctional system in which a chiral nucleophile was paired with an achiral Lewis acid metal salt [73, 74]. Optically enriched (3-lactam products were isolated in high yields, (Scheme 18). Among the various Lewis acids studied, such as Mg(OTf)2, Cu (MeCN)4C104, YbCL. La(OTf)3, AgOTf, Al(OTf)3, Sc(OTf)3, Zn(OTf)2,and In (OTf)3, this latter was the best overall cocatalyst for promoting the reaction. The best chiral nucleophiles used are reported in Scheme 18. 

A chiral alumi n i u m - s a I e n - PI13 PO combination catalyses addition to ketones in up to 92% ee the catalyst system essentially acts as a Lewis acid-Lewis base bifunctional system.248 A similar chiral manganese(III)-salen-Ph3PO method is comparable.249... 

The presence of a metal in low oxidation state is not essential to have a bifunctional system. Indeed, both the acid-base and the redox-active sites can be in high a... 

The most active catalysts for methanol oxidation are presently based on bifunctional systems such as Pt-Ru. Yet the evaluation of a metal-support interaction would require the analysis of a simpler catalytic system (i.e., a monometallic catalyst) this would avoid the interference of all those aspects such as degree of alloying, changes in crystallographic parameters, chemical state of the promoting element, which significantly affect the activity, and thus a comprehensive interpretation of the data actually available. 

The fluorescence of the other chromophore was efficiently but not totally quenched in the bifunctional systems but not at all in equimolar mixtures of the monofunctional models. All phosphorescence, however, occurred from the parabutyrophenone part, indicating very efficient triplet transfer. Bathochromlc shifts and a hyperchromic effect in the longest wavelength band of the absorption spectra are an indication for ground state interaction, which might lead to nonplanar conformations of the molecule playing a role in the excitation transfer. 

For this discussion, an example of the bifunctional system (/= 2) is useful. As has been well-known [6], the bifunctional system has the general solution of the ring concentration written by a couple of equations of the form (the A - R - B model) ... 

Vrbka, L., Klan, P., Kriz, Z., Koca, J., Wagner, P. J., Computer Modeling and Simulations on Flexible Bifunctional Systems Intramolecular Energy Transfer Implications, J. Phys. Chem. A 2003, 107, 3404 3413. 

The intrinsic activity of the bifunctional system has been increased by balanced improvements to both the Pt metal centres by increasing their dispersion, and improved stability of dispersion through improvements to the defect structure and purity of the alumina support, especially iron and sodium levels, for instance, by using alumina derived from the Zeigler process.90 This led to better acid site strength distributions, and improved chloride retention. In addition, reduced levels of iron led to lower rates of coking. 

Very recently, an intramolecular version with a related bifunctional system, activated by titanium(lV) chloride, has been reported. The civ-fused product is obtained as a mixture of stereoisomers, the ratio of which depends on the vinylic substituent X13. 

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