Chiral auxiliary approach

Only few successful reports utilizing the chiral auxiliary approach for the a-hydroxyalkylation of allyllic anions have been made. 

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... 

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

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. 

The asymmetric [3 + 4] cycloaddition is readily achieved using chiral auxiliaries or catalysts [16]. The efficiency of the chiral auxiliary approach is illustrated in the [3-1-4] cycloaddition with cyclopentadiene. The vinyldiazoacetate 6, with (T)-pantolactone as the chiral auxiliary, generated the bicyclo[3.2.1]octadiene 75 in 87% yield and 76% dia-stereomeric excess (Eq. 10) [82]. Alternatively, the chiral rhodium prolinate Rh2(S-DOSP)4-catalyzed reaction of 4 generated the bicyclo[3.2.1]octadiene 76 in 77% yield and with 93% enantiomeric excess (Eq. 11) [83]. 

Asymmetric Induction in Organic Photochemistry via the Solid-State Ionic Chiral Auxiliary Approach... 

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. 

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. 

An advantage of the chiral auxiliary approach was that the minor diastereomer has the potential to be rejected to enhance the diastereomeric purity of the product, and this was in fact achieved in our case. Crystallization from toluene allowed for the isolation of the desired diastereomer in 76% overall yield with 99.0% de purity. 

Overall, the chiral auxiliary approach to sitagliptin using (S)-PGA to install the amino group via diastereoselective hydrogenation resulted in a reduction of three chemical steps in the overall synthesis. This new synthetic approach essenhally followed the same convergent strategy (Route A on Scheme 5.8), but represented a big improvement over our previous route. The convergent approach made sense since the triazole heterocycle was a valuable intermediate that required an elaborate preparation with a modest yield of 26%. 

General Three Carbon Chiral Synthons from Carbohydrates Chiral Pool and Chiral Auxiliary Approaches... 

Scheme 4.14. Chiral auxiliary approach to diastereoselective cyclizations.

The intramolecular diene-carbene cycloaddition equivalence and an enantioselective Birch reduction-alkylation by the chiral auxiliary approach. Total synthesis of ( )- and (—)-longi-folene. Journal of Organic Chemistry,... 

Ramamurthy et al. have examined enantioselective and diastereoselective ODPM rearrangements of cyclohexadienone and naphthalenone derivatives within MY zeolites, where M is an alkali ion [38, 39]. For example, in Scheme 4.27, in NaY in the presence of several chiral inductors such as ephedrine, pseudoephedrine, and camphorquinone-3-oxime, an enantioselective ODPM rearrangement of 65 and 66 took place to afford 68 in 30% ee yield. In the frame of the chiral auxiliary approach, the compound 67 linked to (S)-ephedrine was irradiated within NaY to give 68 in moderate diastereoselective excess (de) (59%). Interestingly, the reaction media of KY, RbY, and CsY reverse the diastereoselectivities. The cation-dependent diastereo-meric switch has been discussed with respect to the N- or O-functional group in 67 [39]. Recently, Arumugan reported that the irradiation of naphthalenones 65 linked chiral auxiliaries (R3 = COO(—)-Ment or (S)-NHCH(Me)Ph) in Li+ or Na + Nafion resulted in chiral products ( 14% de) [40],... 

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