Three-Component Conjugated Processes

an interaction between reactions may be performed both with the help of stable IP (consecutive reactions), intermediate compounds (initiation, conjugated reactions, etc.), and in their absence (a definite type of parallel reactions). Of special interest for us are interrelated reactions performed with the help of labile, highly reactive intermediate compounds. This question will also be discussed below. 

Similar to conjugated (interfering) reactions, parallel reactions must be synchronous, which is their obvious fundamental property. 

Meanwhile, consecutive reactions may never be synchronous. This is the principal difference between these two systems—synchronous and usual reactions. As a matter of fact, the final product of the first stage of consecutive reactions is the initial compound for the second stage, therefore, these stages may never be simultaneous (synchronous). Thus, the main difference between synchronous parallel and conjugated (interfering) reactions is that the first type eliminates even a possibility of interaction, whereas in the second case they may only be interacting reactions. 

Let us now discuss different alternatives associated with the participation of the three main components of the conjugated reaction system (actor, inducer and acceptor) in chemical induction and other forms of chemical interference. 

One of the common types of actor participation in the induction of the secondary reaction is its transformation to a reactive particle under the inducer effect. This newly formed particle then involves another substance (acceptor) in the secondary reaction. Therefore, the actor participates in gross equations of both conjugated reactions which, finally, are reduced to the widespread type of conjugated reactions (2.1) and (2.2). 

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This palladium-catalyzed three-component coupling reaction leading to the formation of aryl-substituted allylic amines was recently adapted to solid-phase synthesis (Scheme 8.23). Amines were chosen to attach to a solid support (Rink resin) in this three-component coupling process and were reacted with a variety of aryl halides and linear or cyclic non-conjugated dienes, the reaction being carried out at 100 °C for two days in the presence of palladium acetate and diisopropylethyl-amine. A wide variety of aryl-substituted allylic amines were then obtained after cleavage from the solid support by trifluoroacetic acid [60],... 

Okada, S., Arayama, K., Murayama, R., Ishizuka, T., Hara, K., Hirone, N., Hata, T., Urahe, H. (2008). Iron-catalyst-switched selective conjugate addition of Grignard reagents a, 3,Y,5-Unsaturated amides as versatile templates for asymmetric three-component coupling processes. Angewandte Chemie International Edition, 47, 6860-6864. 

Barbas developed this procedure further by introducing an asymmetric three-component Michael reaction that should be applicable to many other conjugate addition reactions. He used a Wittig olefmation to prepare, in situ, an a,P-unsatu-rated ketone that subsequently underwent a conjugate addition with malonates (Scheme 21) [94]. The rate of the conjugate addition process was observed to be considerably faster than the analogous reaction reported by Jprgensen which was attributed to the presence of triphenylphosphine oxide within the reaction mixture. 

Dialkylzinc derivatives are inert towards conjugated enones (e.g. 181) in hydrocarbon or ethereal solvents. The discovery that a conjugate addition can be promoted by Cu(I) salts in the presence of suitable ligands L (e.g. sulphonamide 182) opened a new route to zinc enolates (e.g. 183), and hence to the development of three-component protocols, such as the tandem 1,4-addition/aldol addition process outlined in equation 92186. If the addition of the aldehyde is carried out at —78 °C, the single adduct 184 is formed, among four possible diastereomeric products. The presence of sulphonamide is fundamental in terms of reaction kinetics its role is supposed to be in binding both Cu(I) and Zn(II) and forming a mixed metal cluster compound which acts as the true 1,4-addition catalyst. 

Another example of a photoredox molecular switch is based on a ferrocene-ruthenium trisbipyridyl conjugate, in which the luminescent form 4 switches to the non-luminescent form 5 upon electrochemical oxidation (Figure 2/bottom)171. Biological systems exploit the interplay of redox and molecular recognition to regulate a wide variety of processes and transformations. In an attempt to mimic such redox systems, Deans et al. have reported a three-component, two-pole molecular switch, in which noncovalent molecular recognition can be controlled electrochemically. x Willner et al. have reported on their research activities in developing novel means to achieve reversible photostimulation of the activities of biomaterials (see Chapter 6).[91 Recently, we have shown that it is possible to switch the luminescence in benzodi-furan quinone 6 electrochemically. 101 The reduction in THF of the quinone moiety... 

The most suitable kinetic approach was suggested in a textbook by Emanuel and Knorre [1], It discusses a particular widespread case of conjugated processes with three components ... 

A related one-pot three component coupling reaction leading to allyli-dene tetrahydrofuran derivatives 80 and which combines a conjugate addition of a propargyl alcohol with an activated olefin and an in situ palladium-catalyzed carbopalladation-cyclization in the presence of a large excess of allyl chloride has been recently developed by Lu and Iiu (Scheme 31) [77]. The cyclization process is here initiated by addition of a catalytic amount of Pd(OAc)2 and in marked contrast with the above-discussed reactions, a catalytic cycle involving divalent palladium proceeds in the reaction. In this process, the ester enolate formed in the Michael addition undergoes... 

The key element of this protocol is the initial addition of cationic electrophiles such as rerr-alkyl or acyl cations to the double bond of a DCHC complex of the conjugated enyne 118, which results in the formation of the substituted propargylic cation intermediate 119, Subsequent reaction with pre-selected external nucleophiles, for example allylsilanes or silyl enol ethers, leads to the formation of the final adducts 120. The reaction is carried out as a one-pot, three-component coupling and can be used for the creation of two novel C-C bonds. It is a process somewhat complementary to the stepwise Michael addition described earlier (Scheme 2.31), with a reverse order of E and Nu addition. Oxidative decomplexation of 120 yields the product 121. The overall... 

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