Racemization amino alcohols

As described in the section dealing with liquid chromatographic methods, the reaction of 0,0-di-substituted tartaric anhydrides with racemic amino alcohols in acidic solution leads exclusively to the corresponding diastereomeric monoesters, which are easily separated by reversed-phase HPLC. However, H- and sometimes 13C-NMR spectra of these compounds are in many cases also highly useful for determining the diastereomeric ratio and in many cases the absolute configuration. 

Racemic l-dimethylaminopropan-2-ol (18) was acylated with propanoyl chloride, and the reaction product was analyzed by gas chromatography (GC). The resultant (R)- and (5)-esters 19 (R1 = COEt) were resolved by GC using an a-cyclodextrin column. Reaction of the racemic alcohol 18 was then carried out in the presence of Novozyme 435 and vinyl propanoate, and the reaction was followed by GC. After 4 hours the reaction was approximately 2% complete and the ee of the propanoate ester 19 (R1 = COEt) was 95.9%. After 88 hours the conversion had reached 50% and the ee was still 95.6%. The remarkable specificity of Novozyme 435 for the (/O-amino alcohol 1 A )-18 was evident because even after 3.5 days reaction time, only a very small amount of the (5)-ester was detected. The reaction could be scaled up thus, 1 kg of the racemic amino alcohol 18 was treated with vinyl propanoate (0.5 equivalents) and Novozyme 435 (3% by weight). After 3 days, both optically active products were isolated by distillation at reduced pressure. The (5)-amino alcohol (.V)-18 was recovered in 45% yield, which compared favorably with a yield of 32% for resolution on a small scale. The (R)-propanoate 19 (R1 = COEt) distilled as a colorless oil in 36% yield — slightly higher than that obtained from the small-scale resolution. The overall recovery was 81% from the scaled up reaction. 

RESOLUTION OF RACEMIC AMINO ALCOHOLS AND PUIFICATION OF DIASTEREOMERIC AMINO ALCOHOL USING CHIRAL BI-2-NAPHTHOL AND B(OH)3... 

It was anticipated that the amino alcohol would form one of the borate complexes of the type 3-6 with bi-2-naphthol in the presence of boric acid. Indeed, this has been observed. The racemic amino alcohol 8 was resolved to obtain 8-lR,2R in >99% ee in 3 repetitive operation shown in Scheme 7.15 The IR spectrum indicated the presence of hydroxy group in the borate complex involved in this reaction (Scheme 7). However, the solid was not suitable for X-ray crystal structure analysis. Fortunately, however, the corresponding racemic methyl ether 9 gave better results in this resolution method (Scheme 8).15 Also, X-ray crystal structure analysis indicated that the borate complex formed in this reaction is the Bronsted acid salt of the type 5.15 Scheme 8... 

We have also examined the use of chiral bi-2-naphthol to resolve some other racemic amino alcohols. The S-diphenylpyrrolidinemethanol S-10, synthesised from S-proline is useful in the preparation of the CBS oxazaborolidine catalyst,16 widely used in catalytic asymmetric reductions. Accordingly, the corresponding R-10 enantiomer is also a valuable chiral compound. 

It was of interest to examine the use of chiral bi-2-naphthol to resolve the racemic amino alcohol 11 that can be prepared starting from pyroglutamic acid (Scheme 9). Preliminary studies revealed that die resolution can be readily carried out using B(OH)] and chiral bi-2-naphthol (Scheme 9).17 Further optimisation of the results and structural analysis of the borate complex involved in this reaction are under way. 

Non-racemic amino alcohols derived from common amino acids have been employed to prepare acyclic nucleotide analogues (35) with controlled absolute stereochemistry, as structural hybrids of PMEA and PMPA, the propyl homologue of PMEA. L-threonine and L-alanine were used as precursors in... 

The racemic amino alcohol 2 was easy to prepare so one obvious choice is an enzyme-catalysed acylation or deacylation process (chapter 26). These worked reasonably well. Deacylation of the ester-amide 6 gave the amide 5 which was difficult to hydrolyse. Acylation gave the monoester 4 but this equilibrated rapidly with the same amide 5. Both gave the same enantiomer of the amino alcohol and of course the maximum yield is only 50%. 

Rifamycin B resolved several racemic amino alcohols, such as atenolol, alprenolol, ephedrine, norphenylephrine, salbutanol, terbutaline, and others (212). The charge-charge, hydrogen bonding, and hydrophobic inclusion interactions between the negatively charged rifamycin and the amino alcohol provide chiral... 

DW Armstrong, K Rundlett, GL Reid 3rd. Use of a macrocyclic antibiotic, rifamy-cin B, and indirect detection for the resolution of racemic amino alcohol by CE. Anal Chem 66 1690-1695, 1994. 

Et2Zn + RCHO Five racemic amino alcohols 10 chiral amino alcohol activators to induce asymmetric catalysis Zn... 

The Ding approach used a combination of five racemic amino alcohols, and 13 chiral amino alcohols to generate a chiral catalyst library comprising 65 members (Figure 6). 

Kawabata developed chiral DMAP derivative 10 having a bicyclic ring system for kinetic resolution of racemic alcohols in 1997. This method provided an efficient way to resolve racemic monoprotected 1,2-diol derivatives such as 11 with isobutyric anhydride to afford recovered 11 in high enantioselectivity. Racemic amino alcohol derivatives including 12 also resolved effectively in the presence of the catalyst 10 with a selectivity... 

Both enantiomers of mandelic acid are commercially available and these are suitable resolving agents for a variety of functional groups, and often used to isolate chiral alcohols. A sequential use of (R)- and (5)-mandelic acid allowed resolution of racemic amino alcohols (Eq. 3.3) [22]. Subsequent extraction gave 90% recovery of the amino alcohols with 99% ee or better. Mandelic acid was recovered in 93% yield. 

Chiral Amino Alcohol/Zn/Racemic Amino Alcohol-Catalyzed Asymmetric Diethylzinc Addition to Aldehydes... 

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