Dual cascade reactions

Moreover, Heise and Palmans investigated the possibility of conducting both polymerizations as a one-pot cascade reaction in the presence of the dual initiator, ATRP catalyst, CL and methacrylates [16]. The study revealed that certain ATRP catalysts have a strong inhibiting effect on the enzyme. A nickel catalyst, for example, completely inhibited the enzyme, while certain copper catalysts had no... 

Lin, H., Tan, Y, Sun, X.-W, Lin, G.-Q (2012). Highly efficient asymmetric synthesis of enantiopure dihydro-1,2-oxazines dual-organocatalyst-promoted asymmetric cascade reaction. Organic Letters, 14, 3818-3821. 

Double Cascade Reactions Amine-based organocatalysis are often employed for these cascade reactions because they can present a dual-activation mode depending the system involved, via enamine or iminium catalysis. 

Table 43.2 Representative examples of the dual catalyst promoted cascade reaction (Scheme 43.29).

The synergism of a dual-catalyst system comprising of Pt/ZSM-12 and H-Beta aiming to improve the benzene product purity during transalkylation of aromatics has been studied. Catalyst compositions of the dual-catalyst system were optimized at various reaction temperatures in terms of benzene product purity and premium product yields. Accordingly, a notable improvement in benzene purity at 683 K that meets the industrial specification was achieved using the cascade dual-bed catalyst. 

Apart from ATRP, the concept of dual initiation was also applied to other (controlled) polymerization techniques. Nitroxide-mediated living free radical polymerization (LFRP) is one example reported by van As et al. and has the advantage that no further metal catalyst is required [43], Employing initiator NMP-1, a PCL macroinitiator was obtained and subsequent polymerization of styrene produced a block copolymer (Scheme 4). With this system, it was for the first time possible to successfully conduct a one-pot chemoenzymatic cascade polymerization from a mixture containing NMP-1, CL, and styrene. Since the activation temperature of NMP is around 100 °C, no radical polymerization will occur at the reaction temperature of the enzymatic ROP. The two reactions could thus be thermally separated by first carrying out the enzymatic polymerization at low temperature and then raising the temperature to around 100 °C to initiate the NMP. Moreover, it was shown that this approach is compatible with the stereoselective polymerization of 4-MeCL for the synthesis of chiral block copolymers. 

Dual Temperature Process. A unit of a dual temperature cascade is shown schematically in Figure 8. The dual temperature system operates on the principle that isotope exchange reactions, like all chemical reactions, change their equilibrium constants with temperature. The general, but far from universal (22), rule is that in systems with large isotopic... 

This dual enamine/iminium activation profile in cascade Michael/aldol reactions can also be found even in some early reports, mostly focused on the self-dimerization of enals catalyzed by proline or analogues derived thereof, which generally proceeded with low enantioselect vities. There is not a clear and definitive mechanistic pathway confirmed for these reactions, although the most widely accepted proposal for the dimerization of enals (Scheme 7.4) ° involved sequential activation of one molecule of the substrate as a dienamine (Michael donor) and another molecule as iminium ion (Michael acceptor). 

In the second reaction, a Michael-Michael cascade between an unsaturated oxin-doles 17 and enones 22 was shown to be catalyzed by a primary amine-derived catalyst (II) (Scheme 10.3). The reaction afforded the spirooxindoles 23 in excellent yields and diastereo and enantioselectivities. Wang used a similar approach in the reaction of isatylidene malononitriles and enones [12]. The reaction was catalyzed by the dual combination of cinchona-based chiral primary amine and BINOL phosphoric acids to afford the spirocycles in excellent yields (88-99%), diastereo (up to 99 1 dr), and enantioselectivities (95-99% ee). 

Wu and co-workers presented an efficient domino reaction for the rapid synthesis of 5-phenyl-[l,2,3]triazolo[l,5-c]quinazolines derivatives (80) from simple and readily available (E)-l-bromo-2-(2-nitrovinyl)benzenes 79, aldehydes, and sodium azide (Scheme 7.56) [124]. This reaction cascade comprised [3 + 2] cycloaddition, copper-catalyzed SnAt, reduction, cyclization, and oxidation. It is noteworthy that sodium azide is used as a dual nitrogen source in the construction of these fascinating fused A-heterocycles. 

Cyclobutene derivatives (66) have been synthesized from a diyne and an alkene via a novel Au(I)-catalysed reaction. A highly active vinylidene intermediate (67), formed by a dual Au(I)-mediated activation of the diyne precursor, is believed to act as an alkylidene Au(I)-carbenoid to effect stereospecific cyclopropanation of the alkene the resulting methylenecyclopropane (68) converts to (66) via an Au(I)-catalysed ring-expansion cascade. 

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