Chiral inductor

III) Chiral Inductor + Chiral Auxiliary Method (CIAM)... 

Ruano J. L. G., Carretero J. C., Carreno M. C., Cabrejas L. M. M., Urbano A. The Sulfinyl Group As a Chiral Inductor in Asymmetric Diels-Alder Reactions... 

Analogous results were obtained for enol ether bromination. The reaction of ring-substituted a-methoxy-styrenes (ref. 12) and ethoxyvinylethers (ref. 10), for example, leads to solvent-incorporated products in which only methanol attacks the carbon atom bearing the ether substituent. A nice application of these high regio-and chemoselectivities is found in the synthesis of optically active 2-alkylalkanoic acids (ref. 13). The key step of this asymmetric synthesis is the regioselective and chemoselective bromination of the enol ether 4 in which the chiral inductor is tartaric acid, one of the alcohol functions of which acts as an internal nucleophile (eqn. 2). 

The stereochemistry of the first step was ascertained by an X-ray analysis [8] of an isolated oxazaphospholidine 3 (R = Ph). The overall sequence from oxi-rane to aziridine takes place with an excellent retention of chiral integrity. As the stereochemistry of the oxirane esters is determined by the chiral inductor during the Sharpless epoxidation, both enantiomers of aziridine esters can be readily obtained by choosing the desired antipodal tartrate inductor during the epoxidation reaction. It is relevant to note that the required starting allylic alcohols are conveniently prepared by chain elongation of propargyl alcohol as a C3 synthon followed by an appropriate reduction of the triple bond, e. g., with lithium aluminum hydride [6b]. 

Other types of new AT-containing ligands have been described as effective chiral inductors for copper-catalyzed asymmetric cyclopropanation. Hence, Fu and Lo [42] prepared a new planar-chiral hgand, namely the C2-symmetric bisazaferrocene (structure 34 in Scheme 18), which was fbimd to be efficient for the cyclopropanation of various olefins with large diastereomeric excesses and ee values up to 95%. 

To date, direct asymmetric synthesis of optically active chiral-at-metal complexes, which by definition leads to a mixture of enantiomers in unequal amounts thanks to an external chiral auxiUary, has never been achieved. The most studied strategy is currently indirect asymmetric synthesis, which involves (i) the stereoselective formation of the chiral-at-metal complex thanks to a chiral inductor located either on the ligand or on the counterion and then (ii) removal of this internal chiral auxiliary (Fig. 4). Indeed, when the isomerization of the stereogenic metal center is possible in solution, in-... 

The study of alkynylation of methyl ketones using a terminal alkyne, ZnMe2, and a salen derivative 196 as a chirality inductor provided a new method for the preparation of ct-hydroxyacetylenes (197, Scheme 112).292... 

Asymmetric additions of Reformatsky-type reagents to nitrones 258a and 258b have also been reported (Scheme 139). The reagents were prepared in situ from ZnEt2 and the corresponding iodoacetic acid ester. Diisopropyl (R,R)-tartrate 262 was employed as a chiral inductor. Enantioselectivities varied significantly the best results were obtained at 0 °C when a nitrone was added to the reaction mixture over a 2 h period. 

The idea of Hoveyda with co-workers to employ their peptide ligands (e.g., 295) as chiral inductors in allylic substitutions with dialkylzincs turned out to be very rewarding.399-401 As a result of meticulous screening of numerous optically active ligands, copper salts, and substrates under various conditions, they achieved excellent results for aliphatic alkenes. Particularly, allylic substitution products with tertiary 297 and quaternary 299 carbon centers were obtained regioselectively and with 78-96% ee (Scheme 151).401... 

The enantioselectivity of [3+ 2]-cycloaddition reactions is determined by the preference of a particular facial attack of the reagents containing chiral inductors. Most of such reactions proceed in the absence of a catalyst and, consequently, the inductor should be present in either the dipole or the dipolarophile. 

Silyl nitronates containing chiral inductors have not been as yet used in intermolecular [3 + 2]-cycloaddition reactions. In this case, the facial discrimination was generally created by introducing chiral nonracemic fragments into dipolarophiles (see review 433). 

In addition, chiral five-membered cyclic nitronates can be prepared from optically inactive starting nitronates with the use of ligated palladium (catalyst) as a chiral inductor (71) (ee 97%). 

Two research groups examined the approach to the synthesis and the use of six-membered cyclic nitronates by introducing chiral inductors into the molecule of the starting a-nitroalkene. (Here, it is incorrect to use the term auxiliaries because the chiral fragment is not eliminated and is involved in the target product.)... 

This strategy has recently been extended to optically active stereosequences, either by using a chiral protective group (carbamate) as an inductor, or by using (S)- or (R)-BINOL-TiCl2 as the catalyst for the Mukayiama reaction [29]. 

Bidentate chiral auxiliaries have since been examined. While camphane-2,3-diol and (5-binaphthol gave disappointing results, tartrate-derived (TADDOL) ligands were found to be very promising as chiral inductors [44]. Particularly interesting results were obtained by using complex 21, readily available from natural (P,J )-(+)-tartaric acid (Scheme 13.21). 

In more recent times interest has been shown in the effects of constrained environment on the outcome of such reactions. Some enantioselectivity in the product 308 has been reported following the irradiation of benzonorbornadiene 309 in a T1Y zeolite. (—)-Ephedrine was used as the chiral inductor and sensitization brought about the reaction in 30 min. An ee of about 14% was obtained168. 

Scheme 5 Examples of the zeolite chiral inductor and chiral auxiliary methods for photochemical asymmetric synthesis...

Direct condensation of 4, 5-dimethoxy-[2- F]fluorobenzaldehyde with an asymmetric chiral inductor [170] followed by L-selectride reduction of the olefinic double bond and hydrolysis leads to [6- F]fluoro-L-DOPA in 3 % radiochemical yield and an ee higher than 90% (total synthesis time 125 min) (Scheme 34). This method avoids the preparation of F-fluorobenzylhalides. 

An alternative method for the epoxidation of enones was developed by Jackson and coworkers in 1997 , who utilized metal peroxides that are modified by chiral ligands such as diethyl tartrate (DET), (5,5)-diphenylethanediol, (—)-ephedrine, ( )-N-methylephedrine and various simple chiral alcohols. The best results were achieved with DET as chiral inductor in toluene. In the stoichiometric version, DET and lithium tert-butyl peroxide, which was generated in situ from TBHP and n-butyllithium, were used as catalyst for the epoxidation of enones. Use of 1.1 equivalent of (-l-)-DET in toluene as solvent afforded (2/f,35 )-chalcone epoxide in 71-75% yield and 62% ee. In the substo-ichiometric method n-butyllithium was replaced by dibutylmagnesium. With this system (10 mol% Bu2Mg and 11 mol% DET), a variety of chalcone-type enones could be oxidized in moderate to good yields (36-61%) and high asymmetric induction (81-94%), giving exactly the other enantiomeric epoxide than obtained with the stoichiometric system (equation 37). 

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