Sequential resolution racemates

Alternatively, treatment of a mixture of bulbocapnine N-oxides with acetic anhydride at 0 °C led to dehydrobulbocapnine, which could be reduced with zinc and acid to racemic bulbocapnine. Resolution using the tartrate salt provided ( - )-bulbocapnine. The methylenedioxy and the methoxyl groups were sequentially cleaved, by treatment with boron trichloride, to produce the triphenol (29) cleavage with boron tribromide gave rise to the hydrobromide of tetraphenol (30) in good yield. ... 

In the asymmetric reduction of enol acetates, five different reactions take place sequentially deacetylation of enol acetate, keto-enol isomerization, hydrogenation of ketone, and finally racemization and resolution of alcohol for DKR (Scheme 5.10). Here, the enol acetate acts as both the precursor of ketone and the acyl donor. The overall transformation was performed with Novozym 435 and Shvo s catalyst in the presence of hydrogen molecule or 2,6-dimethylheptan-4-ol as the hydrogen donor to provide the products of high enantiopurity with good )delds in most cases (Scheme 5.11 and Chart 5.8). 

In the aqueous phase enzymatic hydrolysis of racemic IPGA leads to IGP (mainly one enantiomer), which can be extracted into the supercritical fluid. Buffering of the pH in the aqueous solution is necessary to provide optimal conditions for the enzyme. In the following lipase-catalyzed esterification IPG reacts with vinyl but) to IPG-butyrate (lipase was from P. cepacia). In this sequential resolution of racemates no processing of intermediates is necessary both reactions take place in different phases (Fig. 19). 

The synthesis of key intermediate 12, in optically active form, commences with the resolution of racemic trans-2,3-epoxybutyric acid (27), a substance readily obtained by epoxidation of crotonic acid (26) (see Scheme 5). Treatment of racemic 27 with enantio-merically pure (S)-(-)-1 -a-napthylethylamine affords a 1 1 mixture of diastereomeric ammonium salts which can be resolved by recrystallization from absolute ethanol. Acidification of the resolved diastereomeric ammonium salts with methanesulfonic acid and extraction furnishes both epoxy acid enantiomers in eantiomerically pure form. Because the optical rotation and absolute configuration of one of the antipodes was known, the identity of enantiomerically pure epoxy acid, (+)-27, with the absolute configuration required for a synthesis of erythronolide B, could be confirmed. Sequential treatment of (+)-27 with ethyl chloroformate, excess sodium boro-hydride, and 2-methoxypropene with a trace of phosphorous oxychloride affords protected intermediate 28 in an overall yield of 76%. The action of ethyl chloroformate on carboxylic acid (+)-27 affords a mixed carbonic anhydride which is subsequently reduced by sodium borohydride to a primary alcohol. Protection of the primary hydroxyl group in the form of a mixed ketal is achieved easily with 2-methoxypropene and a catalytic amount of phosphorous oxychloride. 

Jacobsen has utilized [(salen)Co]-catalyzed kinetic resolutions of tenninal epoxides to prepare N-nosyl aziridines with high levels of enantioselectivity [72], A range of racemic aryl and aliphatic epoxides are thus converted into aziridines in a four-step process, by sequential treatment with water (0.55 equivalents), Ns-NH-BOC, TFA, Ms20, and carbonate (Scheme 4.49). Despite the apparently lengthy procedure, overall yields of the product aziridines are excellent and only one chromatographic purification is required in the entire sequence. 

As well as being applicable to the glycosylation of monohydroxy compounds, the reaction has been used to disubstitute diols such as chloramphenicol (84), to give products of sequential substitution such as 86, and hence saturated glycosylated compounds. In a different type of application, the resolution of the racemate of compound 85 can be accomplished by glycosylation and separation of the diastereomers to afford the illustrated enantiomer which was required for work on the synthesis of taxol. 

In order to obtain levoglucosenone 1 in both enantiomeric forms by employing lipase-mediated kinetic resolution, we used acrolein dimer 2 as the starting material.4 2 was first transformed to the bicyclic ketone ( )-6 by sequential four steps of reactions via 3-5. Racemic levoglucosenone ( )-l was obtained from 6 via the silyl ether 7 by employing the Saegusa reaction. To carry out lipase-mediated resolution, ( )-l was transformed into the e/wfo-alcohol ( )-8 and the acetate ( )-9 (Scheme 1). 

Information about the degree of configurational stability of allenyltitanium compounds has been provided by Hoffmann and Hoppe (Scheme 35). Racemic allenyltitanium reagent (3) is prepared by sequential treatment of 3-methoxy-1,2-butadiene (2) with n-butyllithium and titanium tetraisopropoxide. In the reaction of the racemate with one equivalent of (S)-(4) or its racemate, products (5)-(8) are formed in 70-90% total yield in the ratios shown in Scheme 35. Since the product ratios from the two experiments are different, the equilibrium between the enantiomers of (3) must be slow compared to the rate of reaction of (3) with (4). Thus, (S)-(3) leads to (5) + (6) and (R)-(3) leads to (7) + (8) (i.e. 51 49). From experiment B, the combinations (S)-(3) + (S)-(4) and (/ )-(3) -t- (/ )-(4) are shown to react considerably more rapidly than that of the (R)/(.S) pairs (mutual kinetic resolution). ... 

Sequential Biocatalytic Resolutions. For a racemic substrate bearing tv o chemically and stereochemically identical reactive groups, an enzymatic resolution proceeds through two consecutive steps via an intermediate monoester stage. During the course of such a reaction the substrate is forced to enter the active site... 

Scheme 3.6), the resolution of a racemic alcohol can be effected by enantioselec-tive hydrolysis of the corresponding ester or by esterification of the alcohol. As the biocatalyst displays the same stereochemical preference in both reactions, the desired product can be obtained with higher optical yields, if the two steps are coupled sequentially. The basis of this approach parallels that of product recycling in hydrolytic reactions. However, tedious chromatographic separation of the intermediates and the accompanying re-esterification is omitted. 

S. Roy, K. Chen, Org. Lett. 2012,14, 2496-2499. Three-component organocascade kinetic resolution of racemic nitroal-lylic acetates via sequential iminium/enatnine asymmetric catalysis. 

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. 

The enantioselectivity was measured in preceding experiments to = 1.8 for the hydrolysis and E = 3.6 for the esterification with vinyl butyrate in hexane, and reached E = 10.3 in the overall sequential reaction. By this new method of conducting a resolution of racemates a high enantioselectivity can be reached. 

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