Backbone enantioselective synthesis

Phosphine ligands based on the ferrocene backbone are very efficient in many palladium-catalyzed reactions, e.g., cross-coupling reactions,248 Heck reaction,249 amination reaction,250 and enantioselective synthesis.251 A particularly interesting example of an unusual coordination mode of the l,l -bis(diphenylphosphino)ferrocene (dppf) ligand has been reported. Dicationic palladium(II) complexes, such as [(dppf)Pd(PPh3)]2+[BF4 ]2, were shown to contain a palladium-iron bond.252,253 Palladium-iron bonds occur also in monocationic methyl and acylpalladium(II) complexes.254 A palladium-iron interaction is favored by bulky alkyl substituents on phosphorus and a lower electron density at palladium. 

In the following, the concept of micro modular process engineering is introduced together with the backbone interface developed in order to realize this modular approach. The integration of sensors and an electronic bus system is also described, and the physical characterization of the backbone is discussed within a case study of the enantioselective synthesis of organoboranes. Within the second case study, the sulfonation of toluene with gaseous sulfur tri oxide, the backbone system together with the micro structured devices used is finally assessed based on its application to chemical synthesis. 

One case study within the framework of this project is thus to test the concept of a micro structured reactor plant by applying the fast reaction of the enantioselective synthesis via organoboranes yielding chiral-substituted alcohols. This is typically a batch process carried out in the laboratory using conventional glassware and in the present case has been converted into a continuous process carried out by micro structured devices. This set-up has been used to characterize the physical properties of the backbone system. 

In 2003, Bonini et al. reported a new synthesis of ferrocenyloxazolines based on an iodide-mediated ring expansion of A-ferrocenoyl-aziridine-2-carboxylic esters. The thus-formed ligands were successfully employed as palladium chelates for the test reaction, since they allowed the product to be formed in quantitative yields and good to high enantioselectivities (Scheme 1.69). According to the results, it seemed that the additional chiral centre present in the oxazoline backbone of these ligands did not play a major role for the asymmetric induction and the activity of the corresponding catalysts. 

In 2004, Ricci et al. reported the synthesis of several novel ligands based on an oxazoline-cyclopenta[Z)]thiophene backbone, as depicted in Scheme 2.15. Moderate yields combined with enantioselectivities of up to 79% ee were obtained for the 1,4-product resulting from the copper-catalysed enantioselective... 

In 1998, Ruiz et al. reported the synthesis of new chiral dithioether ligands based on a pyrrolidine backbone from (+ )-L-tartaric acid. Their corresponding cationic iridium complexes were further evaluated as catalysts for the asymmetric hydrogenation of prochiral dehydroamino acid derivatives and itaconic acid, providing enantioselectivities of up to 68% ee, as shown in Scheme 8.18. 

The synthesis of the first polymer-supported chiral Mn-salen derivatives was reported independently by Sivaram171 and Minutolo.171-173 Different monomeric Jacobsen-type units, containing two polymerizable vinyl groups, were copolymerized with styrene and divinylbenzene to yield the corresponding cross-linked polymers as a monolithic compact block.174-176 The less mobile system (Figure 19) with no spacer between the aromatic ring and the polymer backbone is less enantioselective. 

The first catalytic 1,4-addition of diethylzinc to 2-cyclopentenone with over 90% ee was described by Pfaltz and Escher, who used phosphite 54 with biaryl groups at the 3,3 -positions of the BINOL backbone.46 Chan and co-workers achieved high enantioselectivity in the same reaction (up to 94% ee) by using chiral copper diphosphite catalyst (R,R,R)-41 48,48a 48d Hoveyda and co-workers used ligand 46 to realize excellent enantiocontrol (97% ee) in the 1,4-additions of 2-cyclopentenones,52 which may be used in the practical asymmetric synthesis of some substituted cyclopentanes (including prostaglandins). 

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