Auxiliary Braun

Waldmann H., Braun M. Amino Acid Esters As Chiral Auxiliaries in Asymmetric Cycloadditions Gazz. Chim. Ital. 1991 121 277-284... 

Braun, K. R., and H. Kunz. Chiral Auxiliaries in Cycloadditions, Wiley-VCH, 1999. 

H. Waldmann and M. Braun, Amino acid esters as chiral auxiliaries in asymmetric cycloaddi-tions, Gazz. Chim. Ital. 121 111 (1991). 

Riick-Braun K, Kunz H (1999) Chiral Auxiliaries in Cycloaddition. Wiley-VCH, Weinheim... 

As shown in Scheme 9-57, the Ci-Cf, ketones 202 and 203 have both been prepared by aldol chemistry. The synthesis of ketone 202 used the Braun auxiliary 204 in a lithium-mediated aldol reaction and afforded adduct 205 in 75% yield and 98% ds [75]. This synthe.sis can be compared with the related Reformatsky reaction of imide 206, again controlled by an auxiliary attached to the enolate... 

In the middle of the 198O s some silyl enolates derived from homochiral esters were reported to enable highly enantioselective synthesis of aldols [106]. Later, Oppolzer et al. disclosed the utility of camphor sultam as a chiral auxiliary for asymmetric aldol reactions [107]. Braun et al. have recently achieved high levels of asymmetric induction in the aldol reaction of ketones with homochiral silyl enolate 43 (Scheme 10.38) [108]. 

Due to the importance of polypropionate antibiotics, mainy chiral auxiliaries have been introduced on propionic add derivatives in order to perform asymmetric aldol reactions. The use of esters of chiral alcohols usually gives disappointing results [147, 209]. In an important exception, Braun and Sacha [149] recommended the propionate of a trimethylsilyloxyalcohol 1.12. The reaction of the derived dicyclopentylchlorozirconium enolate with aliphatic aldehydes at -105°C leads to anti aldols with an excellent fedal stereoselectivity (Figure 6.78). The selectivity is lower with benzaldehyde. The use of titanium enolates of N-tosyl-aminoephedrine 1.61 (R = Ts) propionate has recently been advocated [1262],... 

DR Schaad. Chem Rev 1996 96 835. (c) J Seyden-Penne Chiral Auxiliaries and Ligands in Asymmetric Synthesis. Wiley, New York, 1995. (d) K Ruck-Braun, H Kunz. Chiral Auxiliaries in Cycloadditions. Wiley-VCH, Weinheim, 1999. 

Chiral auxiliaries in cycloadditions / Karola RUck-Braun Horst Kunz. -Weinheim New York Chichester Brisbane Singapore Toronto WILEY-VCH, 1999 ISBN 3-527-29386-8... 

Braun, R.J., Gummalla, M., and Yamanis, J. (2009) System architectures for solid oxide fuel cell-based auxiliary power units in future commercial aircraft applications. J. Fuel Cell Set. Technol., 6, 031015. 

The auxiliaries R) and (S)-triphenylglycol 172 were also applied to achieve anti-selective propionate aldol additions, as shown by Braun and coworkers. It turned out that, for this purpose, the tertiary hydroxyl group of the propionate (R)-204 had to be protected by silylation. This was easily accomplished by a one-pot procedure that delivered the ester (R)-205. After deprotonation with LICA, the lithium enolate was transmetallated with dichloro(dicyclopentadienyl)zirconium and reacted with aliphatic aldehydes to give predominantly anti-diastereomers 206, the diastereomeric ratio surpassing 95 5. Reduction with lithium aluminum hydride finally led to diols 207 under the release of the chiral auxiliary R)-172. After its removal by chromatography, diastereomerically pure diols 207 were isolated with >95% ee (Scheme 4.45) [107]. For the benzaldehyde adduct 206 (R = Ph), alkaline hydrolysis was also performed and found to lead to epimerization to only a small degree. 

Fluvastatin (28, Scheme 2.4) is a member of the 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG CoA) reductase inhibitor family and is prescribed to treat hypercholesterolemia. As part of their nonracemic synthesis of fluvastatin, researchers at Novartis used a monoacetyltri-phenylglycol chiral auxiliary 25 originally reported by Braun and Devant. A diastereoselective lithium aldol reaction between Braun and Devant s reagent 25 and the fluarophenylindolenal 24 afforded the allylic alcohol 26 as... 

Several acetate containing chiral auxiliaries have been employed as reagents for asymmetric Aldol reactions in drug discovery programmes. Perhaps the most significant of these is Braun s reagent which has been used in the synthesis of hoth atorvastatin and fluvastatin. ... 

Atorvastatin, 217, a HMG-CoA inhibitor developed by Pfizer is a popular treatment for hypercholesterolemia. An early as)mimetric synthesis of the drug used an aldol reaction between the magnesium enolate of Braun s reagent 214 and aldehyde 213 to afford alcohol 215 in 97% ee and 60% yield (Scheme 14.75). Subsequent transesterification was used to remove the chiral auxiliary affording compound 216. 

One of the pervasive problems in asymmetric synthesis has been the development of stereoselective acetate ester aldol reactions. Although a number of chiral auxiliaries perform superbly well in diastereoselective propionate aldol additions, these have, with rare exceptions, been unsuccessful in the corresponding additions of unsubstituted acetate-derived enolates [19, 63, 64). Braun s disclosure of a stereoselective acetate aldol addition reaction with 103 was an important milestone in the development of the field (Scheme 4.11) [63, 65]. The diol auxiliary can easily be prepared from mandelic acid esterification of the secondary alcohol is obsei ved, without interference from the tertiary counterpart. Its use has been showcased in a number of syntheses [53]. The high yield and diastereoselectivity generally obtained with 103 were highlighted by investigators at Merck in the construction of the chiral lactone fragment that is common in a number of HMG-CoA reductase inhibitors, such as compactin (105) [66]. 

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