Model substrates hydrogenation

The activity and enantioselectivity of chiral Ir catalysts have been tested by using 2,3,3-trimethylindolenine as a model substrate. Hydrogenation of the cyclic imine with [Ir(bdpp)Hl2 2 gives the corresponding chiral amine with 80% ce (Scheme 1.99) [350]. The stereoselectivity is somewhat better than that with acyclic substrates (see Scheme 1.94). A neutral BCPM-Ir complex with Bil3 effects asymmetric hydrogenation in 91% optical yield [354], A complex of MCCPM shows similar enantioselection [354], These complexes are not applicable to the reaction of other acyclic and six-membered cyclic imines. An MOD-DIOP-Ir complex is also usable with the aid of ( -C4H9)4NI [355], An Ir complex of BICP with phthalimide effectively... 

Using glucose as a model substrate, hydrogen production is accompanied with either acetate formation (Eq. (15.1) or butyrate formation (Eq. (15.2) (Miyake, 1998). In the acetate fermentation 4 ATPs are produced whereas, 3 ATPs are produced in the butyrate fermentation. Thus, it seems that the acetate fermentation is energetically more favorable than the butyrate fermentation. However, acetate and butyrate fermentations are commonly carried... 

In outline of what follows we will begin by brief reference to previous work on coal liquefaction. The present approach will then be motivated from considerations of coal structure and hydro-gen-donor activity. A theoretical section follows in the form of a pericyclic hypothesis for the coal liquefaction mechanism, with focus on the hydrogen transfer step. Experiments suggested by the theory are then discussed, with presentation of preliminary results for hydrogen transfer among model substrates as well as for the liquefaction of an Illinois No. 6 coal to hexane-, benzene-, and pyridine-solubles by selected hydrogen donors. 

An illustration of how the overall pericyclic mechanism might apply to the decomposition of 1,2 diphenylethane, a model substrate, in the presence of A1-dihydronaphthalene, a model hydrogen-donor, has recently been given (17). In the present work, attention is focussed on the hydrogen-transfer step. 

To illustrate how this applies in the present circumstances we consider a passible group transfer reaction between A2 dihydro-naphthalene, (gQ) > a hydrogen donor, and phenanthrene,(g gr > a substrate (hydrogen acceptor) which models a polynuclear aromatic moiety commonly found in coal. In the overall group transfer reaction ... 

UlluPHOS [43, 44], catASium M [48, 95], Kephos [45, 96] and Butiphane [97] - four ligand systems which possess larger P-Rh-P bite angles than DuPhos [44, 46, 97] - all achieved enantioselectivities >95% when used in the hydrogenation of some model substrates. Much importance has been attached to P-Rh-P bite angles larger than the parent DuPhos system. It is believed that the pos-... 

Cyclic imines do not have the problem of syn/anti isomerism and therefore, in principle, higher enantioselectivities can be expected (Fig. 34.8). Several cyclic model substrates 6 were hydrogenated using the Ti-ebthi catalyst, with ee-val-ues up to 99% (Table 34.5 entry 5.1), whereas enantioselectivities for acyclic imines were <90% [20, 21]. Unfortunately, these very selective catalysts operate at low SCRs and exhibit TOFs <3 h-1. In this respect, iridium-diphosphine catalysts, in the presence of various additives, seem more promising because they show higher activities. With several different ligands such as josiphos, bicp, bi-... 

Until recently, the hydrogenation of enamines has scarcely been investigated. Results have been reported for model substrates 17 and 18, indicating that such transformations are possible in principle (Fig. 34.12). Substrate 17 was hydrogenated with Ir-diop with ee-values of 60-64% and with Rh-bdpch with 72% ee... 

There is little doubt that the hydrogenation of dehydro a-amino acids is the best-studied enantioselective catalytic reaction. This was initiated by the successful development of the L-dopa process by Knowles (see below) and for many years, acetylated aminocinnamic acid derivatives were the model substrates to test most newly developed ligands. As can be seen below, this is the transformation most often used for the stereoselective synthesis of a variety of pharma and... 

Recent results have shown that a number of other commercially available ligands can be expected to have industrial potential for the hydrogenation of dehydro a-amino acid derivatives. However, it must be pointed out that in most cases model substrates and not industrially relevant targets have been investigated until now. Chiral Quest has shown that Rh-TangPhos as well as Rh-f-Ke-talPhos (for structures, see Fig. 37.9) were able to hydrogenate a variety of a-de-hydro amino acid derivatives with ee-values of 98->99%, TONs of up to 10000... 

In contrast to dehydro a-amino acids, the hydrogenation of acetylated /1-dehy-droamino acid derivatives has only recently been of industrial interest and, accordingly, no applications on a larger scale have yet been reported. Several ligands such as certain phospholanes or phosphoramidites might have industrial potential, but until now these have only been tested on model substrates under standard conditions [50]. Chiral Quests TangPhos and Binapine (Fig. 37.10) have been shown to hydrogenate several acetylated dehydro / -amino acid derivatives with ee-values of 98-99% and TONs of 10000 at r.t., 1 bar [3, 47]. 

The hydrogenation of enamides and enol acetates without acid function is often more demanding, and at present is not applied widely. Besides a bench-scale application by Roche with a Ru-biphep catalyst [55], two examples are of interest a pilot process for a cyclic enol acetate by Roche [55], and a feasibility study by Bristol-Myers Squibb [56], both using Rh-DuPhos catalysts (Fig. 37.11). In the latter case, despite very good ee-values, a chiral pool route was finally chosen. Chiral Quests Rh-f-KetalPhos (see Fig. 37.9) has been shown to hydrogenate a variety of substituted aryl enamide model substrates at r.t., 1 bar, with very promising catalyst performance (ee 98-99%, TON 10000) [47]. 

Based on hydrogenations of model substrates, several new ligands promise to have a similar potential as those described above. For example, Ru-Solphos (Solvias) catalysts have been shown to hydrogenate various yS-keto esters and / -diketones with ee-values up to >99% and TONs of up to 100000 (for ethyl-3-oxobutanoate) [75], while Ru-Synphos (Synkem) [107] catalysts achieved 99.4% ee at an SCR of 7000 for the hydrogenation of ethyl acetoacetate (for ligand structures, see Fig. 37.28). 

Iridium nanoparticles prepared in imidazolium-based ILs have been also used in the catalytic hydrogenation of ketones under mild conditions [50]. Firstly, cyclohexanone was chosen as the model substrate to optimize the reaction conditions (temperature, hydrogen pressure, catalyst concentration). Initially, isolated lr(0) nanoparticles were tested in a solventless system for the hydrogenation of cyclohexanone the prehminarily results are listed in Table 15.6. 

Figure 6.46 (A) Hydroxy-protected thiourea 141 and 142 lacking the hydroxy function and their catalytic efficiency in the Friedel-Crafts alkylation of indole with frans-P-nitrostyrene (139 78% yield 85% ee under identical conditions). (B) Proposal for the key hydrogen-bonding interactions between 139 and the model substrates.

A new family of chiral ligands for asymmetric homogeneous hydrogenation has been developed. The performance of mono- and bis-rhodium complexes of these chiral ferrocene tetraphosphine ligands in the hydrogenation of model substrates was surveyed in comparison to their ferrocene bis-phosphine analogs. 

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