Multifunctional Nucleophilic

Multifunctional nucleophiles may undergo 1,4-conjugate addition to the double bond, followed by reaction at the carbonyl moiety to give heterocycHc products (15—18). 

Abstract The dimerization of 1,3-dienes (e.g. butadiene) with the addition of a protic nucleophile (e.g. methanol) yields 2,7-octadienyl ethers in the so-called telomerization reaction. This reaction is most efficiently catalyzed by homogeneous palladium complexes. The field has experienced a renaissance in recent years as many of the platform molecules that can be renewably obtained from biomass are well-suited to act as multifunctional nucleophiles in this reaction. In addition, the process adheres to many of the principles of green chemistry, given that the reaction is 100% atom efficient and produces little waste. The telomerization reaction thus provides a versatile route for the production of valuable bulk and specialty chemicals that are (at least partly) green and renewable. The use of various multifunctional substrates that can be obtained from biomass is covered in this review, as well as mechanistic aspects of the telomerization reaction. 

One aspect of asymmetric catalysis has become clear. Every part of the molecule seems to fulfill a role in the process, just as in enzymic catalysis. Whereas many of us have been used to simple acid or base catalysis, in which protonation or proton abstraction is the key step, bifunctional or even multifunctional catalysis is the rule in the processes discussed in this chapter.Thus it is not only the increase in nucleophilicity of the nucleophile by the quinine base (see Figures 6 and 19), nor only the increase in the electrophilicity of the electrophile caused by hydrogen bonding to the secondary alcohol function of the quinine, but also the many steric (i.e., van der Waals) interactions between the quinoline and quinuclidine portions of the molecule that exert the overall powerful guidance needed to effect high stereoselection. Important charge-transfer interactions between the quinoline portion of the molecule and aromatic substrates cannot be excluded. 

Calixcrown 5, featuring two diethylaminomethyl side-arms at the polyether bridge, testifies an attempt at a higher order multifunctional catalysis of ester cleavage, namely, from nucleophilic-electrophilic to nucleophilic-electrophilic-general acid catalysis [20]. 

This notation blends smoothly with the plus-minus notation to indicate sequences of reactions or multifunctional reagents. In the simple, hypothetical transformation in Scheme 20, dibromomethane might serve as a reagent for the synthon (5). A slash (/) separates the two symbols (-/ ) to indicate that (5) will behave separately as a nucleophilic site and a radical site, rather than as a radical anion. The more rigorous notation of Seebach avoids this confusion. Related transformations have actually been executed by Wilcox and Gaudino.76... 

A range of methods has been developed for the protection of the carbonyl group in multifunctional aliphatic and alicyclic aldehydes and ketones. This has been necessary because in many multistage syntheses, modification of other functionalities (e.g. oxidation, reduction, hydrolysis, nucleophilic and electrophilic additions and displacements, etc.) requires a differing range of experimental conditions, and that protective group must be selected which is stable in the presence of the reaction medium. A further feature that should be noted is that... 

Among the most widely used components for MCRs involving amines and carbonyls are the isocyanides (isonitriles) 26, which were initially used in the Pass-erini reaction [21] and more extensively in a series of MCRs introduced by Ugi (Scheme 7.4) [1, 5, 22], The great effectiveness of isocyanides in MCRs is apparently a result of their remarkable balance between nucleophilic and electrophilic reactivity that enables them to be relatively unreactive towards carbonyl compounds but quite reactive with activated derivatives such as the corresponding imi-nium species. Numerous applications of isocyanides in MCRs leading to a variety of novel multifunctional derivatives and heterocyclic systems have appeared in recent years [5-9]. 

Multifunctional coupling agents, bearing several (>2) identical nucleophilic functions sufficiently separated in space to avoid steric hindrance, may be used to link together similar living macromolecular chains. Well defined star structures are obtained when these nucleophilic functions add cleanly and efficiently to the living ends without any side reaction. It is necessary to use strictly stoichiometric concentrations of the chain ends and of the nucleophilic functions to achieve the target structure and to avoid purification. 

An important advantage of the use of such added nucleophiles is that it allows controlled/living cationic polymerization of alkyl vinyl ethers to proceed at +50 to +70°C [101,103], relatively high temperatures at which conventional cationic polymerizations fail to produce polymers but result in ill-defined oligomers only, due to frequent chain transfer and other side reactions. Recently, initiators with functionalized pendant groups [137] and multifunctional initiators [ 138—140] have been developed for the living cationic polymerizations with added nucleophiles. 

Here, we shall focus on ruthenium-catalyzed nucleophilic additions to alkynes. These additions have the potential to give a direct access to unsaturated functional molecules - the key intermediates for fine chemicals and also the monomers for polymer synthesis and molecular multifunctional materials. Ruthenium-catalyzed nucleophilic additions to alkynes are possible via three different basic activation pathways (Scheme 8.1). For some time, Lewis acid activation type (i), leading to Mar-kovnikov addition, was the main possible addition until the first anfi-Markovnikov catalytic addition was pointed out for the first time in 1986 [6, 7]. This regioselectiv-ity was then explained by the formation of a ruthenium vinylidene species with an electron-deficient Ru=C carbon site (ii). Although currently this methodology is the most often employed, nucleophilic additions involving ruthenium allenylidene species also take place (iii). These complexes allow multiple synthetic possibilities as their cumulenic backbone offers two electrophilic sites (hi). 

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