Auxiliary substrate concept

Another approach, developed in our laboratory, consists of the compartmentalization of the sensing layer25"27. This concept, only applicable for multi-enzyme based sensors, consist in immobilizing the luminescence enzymes and the auxiliary enzymes on different membranes and then in stacking these membranes at the sensing tip of the optical fibre sensor. This configuration results in an enhancement of the sensor response, compared with the case where all the enzymes are co-immobilized on the same membrane. This was due to an hyperconcentration of the common intermediate, i.e. the final product of the auxiliary enzymatic system, which is also the substrate of the luminescence reaction, in the microcompartment existing between the two stacked membranes. 

We have proposed the concept of electroauxiliary,10 which activates substrate molecules toward electron transfer and controls a reaction pathway that would favor the formation of the desired products. For example, preintroduction of an electroauxiliary such as a silyl group to a carbon a to nitrogen gives rise to selective introduction of a nucleophile on the carbon to which the auxiliary has been attached. The use of a silyl group as electroauxiliary was... 

A promising unprecedented application of the chiral enecarbamates Ic in asymmetric synthesis is based on the ship-in-the-bottle strategy, which entails the oxidation of these substrates in zeolite supercages . In this novel concept, presumably dioxetanes intervene as intermediates, as illustrated for the oxidation of the chiral enecarbamate Ic in the NaY zeolite (Scheme 6). By starting with a 50 50 mixture of the diastereomeric enecarbamates (45, 3 R)-lc and (45, 3 5 )-lc, absorbed by the NaY zeolite, its oxidation furnishes the enantiomerically enriched (ee ca 50%) S -methyldesoxybenzoin, whereas the (4R,3 R)-lc and (4R,3 S)-lc diastereomeric mixture affords preferentially (ee ca 47%) the R enantiomer however, racemic methylbenzoin is obtained when the chirality center at the C-4 position in the oxazolidinone is removed. Evidently, appreciable asymmetric induction is mediated by the optically active oxazolidinone auxiliary. 

Although desirable, the recovery of a chiral auxiliary is not always crucial. Some techniques employ a, -unsaturated carbonyl compounds containing a disposable stereogenic center, which is removed after the (asymmetric) conjugate addition step has been performed. This concept appears to be useful only if the chiral substrate is easily accessible in high enantiomeric purity. 

For the preparation of enantiopure amines, diastereoselective synthesis using a chiral auxiliary can be a viable approach. In this concept, in the first step a chiral intermediate is formed by reaction of a prochiral substrate with the chirality transfer agent. The key second step is a diastereoselective reaction. This is followed by cleavage of the chiral auxiliary to give the product amine. This concept is illustrated in Figure 25.1. 

The concept of efficient and selective synthesis in water has been confirmed as the rates, yields, and selectivity were observed for many reactions. Some of the reactions that were only considered possible in organic solvents are now being conducted using water as solvent, and this is very much at the forefront of solvent-replacement research following green chemistry principles. The low solubility of substrates in pure water at room temperature can often be overcome by use of organic cosolvents, ionic derivatization, surfactants, or hydrophilic auxiliaries. 

With the first three chiral auxiliaries, 8a-c, low to medium e.e.s of 7 were obtained, far from values needed to make the process operate on a large scale. Somewhat higher enantioselectivities were obtained when the reaction was performed at —40°C with an N-para-methoxybenzoyl (PMB)-protected substrate 9 (Scheme 13.3). Even more important for the research concept than just enhancement of e.e.s were the observations made in these experiments. First, 2 mol of the acetylide and 2 mol of the chiral auxiliary were needed for complete ketone alkynylation. Second, pyrolidino-ephedrine 8d proved to be the best auxiliary amino-alcohol. With this auxiliary, an e.e. of over 98% was achieved, with complete conversion of the ketone, but only when the acetylide-alkoxide solution was first warmed to 0°C then cooled down to —40°C before addition of the ketone 9 (Scheme 13.3). 

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