Ionic chiral auxiliary

Scheffer JR, Xia W (2005) Asymmetric Induction in Organic Photochemistry via the Solid-State Ionic Chiral Auxiliary Approach. 254 233-262 Schenning APHJ, see Ajayaghosh A (2005) 258 83-118 Schepers U, see Hahn F (2007) 278 135-208 Schindler J, see Faigl F (2007) 269 133-157... 

Ionic Chiral Auxiliary-Induced Asymmetric Induction in Solid-State Organic Photochemistry... 

The first reported use of ionic chiral auxiliaries in asymmetric synthesis was the work of Gudmundsdottir, Scheffer, and Trotter on the di-Tt-methane photorearrangement of the dibenzobarrelene system 33 [31]. Of a number of chiral auxiliaries tested,best results were obtained with prohne fert-butyl ester, which led to dibenzosemibullvalene derivative 34 in an enantiomeric excess of 95% at 40% conversion following diazomethane workup. By determining the ab-... 

A second example of the use of ionic chiral auxiliaries for asymmetric synthesis is found in the work of Chong et al. on the cis.trans photoisomerization of certain cyclopropane derivatives [33]. Based on the report by Zimmerman and Flechtner [34] that achiral tmns,trans-2,3-diphenyl-l-benzoylcyclopropane (35a, Scheme 7) undergoes very efficient (0=0.94) photoisomerization in solution to afford the racemic cis,trans isomer 36a, the correspondingp-carboxylic acid 35b was synthesized and treated with a variety of optically pure amines to give salts of general structure 35c (CA=chiral auxiliary). Irradiation of crystals of these salts followed by diazomethane workup yielded methyl ester 36d, which was analyzed by chiral HPLC for enantiomeric excess. The results are summarized in Table 3. 

The photochemical reaction that has been most thoroughly investigated from the ionic chiral auxiliary point of view is the well-known Norrish/Yang type II reaction. One example, taken from the work of Patrick, Scheffer, and Scott [36], deals with derivatives of 7-methyl-7-benzoylnorbornane-p-car-boxylic acid (37a, Scheme 8). This compound was treated with a variety of optically pure amines to afford the corresponding 1 1 salts (37b), and in an... 

Fig. 1 a Crystal structure of the carboxylate anion portion of the (R)-(+)-l-phenylethyl-amine salt of keto-acid 37a before irradiation, and b after 70% conversion to the corresponding cyclobutanol (ionic chiral auxiliary not shown)... 

It is important to mention again at this point that a general feature of the solid-state ionic chiral auxiliary approach to asymmetric synthesis is that not all chiral auxiliaries lead to high enantiomeric excesses. A case in point is found in the work of Natarajan et al. on the a-oxoamide-containing salts 43 (Scheme 10) [29]. Like the nonionic a-oxoamides discussed previously (Sect. 2.2), these compounds undergo photocyclization to p-lactam derivatives, and while the prolinamide salt behaves perfectly, leading to p-lactam 44 in 99% ee at 99% conversion, the corresponding 1-phenylethylamine salt affords nearly racemic photoproduct (3% ee at 99% conversion). The reason for this difference is... 

Scheme 10 Ionic chiral auxiliary-induced asymmetric induction in a-oxoamide photochemistry...

Scheme 11 The ionic chiral auxiliary approach to asymmetric induction in a Norrish-type cleavage reaction...

Comparison of the Solid-State Ionic Chiral Auxiliary Method of Asymmetric Synthesis with the Pasteur Resolution Procedure... 

Fig. 4 Comparison of the solid-state ionic chiral auxiliary method of asymmetric synthesis with the Pasteur resolution procedure...

Like other methods of asymmetric synthesis, the solid-state ionic chiral auxiliary procedure has an advantage over Pasteur resolution in terms of chemical yield. The maximum amount of either enantiomer that can be obtained by resolution of a racemic mixture is 50%, and in practice the yield is often considerably less [47]. In contrast, the ionic chiral auxiliary approach affords a single enantiomer of the product, often in chemical and optical yields of well over 90%. Furthermore, either enantiomer can be obtained as desired by simply using one optical antipode or the other of the ionic chiral auxiliary. 

Abstract After a brief introduction and summary of various methods of asymmetric induction in organic photochemistry, the main part of the review covers the solid-state ionic chiral auxiliary approach to asymmetric photochemical synthesis. Application of this technique to the Norrish type II reaction, as well as to the di-n-methane and oxa-di-n-methane photorearrangements, and the cis,trans-photoisomerization of diarylcyclopropane derivatives is presented and discussed. 

Ionic chiral auxiliaries Crystal structure-reactivity correlations... 

To this point, all the examples presented have been ones in which the origin of the asymmetric induction has been unimolecular in nature, that is, the molecules adopt homochiral conformations in the solid state that favor the formation of one enantiomer over the other, usually through the close intramolecular approach of reactive centers bimolecular crystal packing effects appear to play little or no role in governing the stereochemical outcome of such reactions. This raises the interesting question of whether the soUd-state ionic chiral auxiliary approach to asymmetric synthesis could be made to work for conformationally unbiased reactants, i.e., those possessing symmetrical, conformationally locked structures. Two such cases are presented and discussed below. 

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