Acetate enantiotopic

In contrast to the hydrolysis of prochiral esters performed in aqueous solutions, the enzymatic acylation of prochiral diols is usually carried out in an inert organic solvent such as hexane, ether, toluene, or ethyl acetate. In order to increase the reaction rate and the degree of conversion, activated esters such as vinyl carboxylates are often used as acylating agents. The vinyl alcohol formed as a result of transesterification tautomerizes to acetaldehyde, making the reaction practically irreversible. The presence of a bulky substituent in the 2-position helps the enzyme to discriminate between enantiotopic faces as a result the enzymatic acylation of prochiral 2-benzoxy-l,3-propanediol (34) proceeds with excellent selectivity (ee > 96%) (49). In the case of the 2-methyl substituted diol (33) the selectivity is only moderate (50). 

For example, the two carbonyl groups in methyl l-methyl-2,5-dioxocyclopentane acetate are enantiotopic and the two faces of each carbonyl group are diastereotopic. Yeast reduction furnished 1 (albeit in low chemical yield), by attack of the pro-R carbonyl group from its sterically less hindered Re-face. The immediate lactone formation indicates the relative configuration at the two stereogenic centers, while the absolute configuration of the yeast reduction product had to be determined (see p 437)133. 

EEAC has been used successfully in other enantiotopic differentiations. Johnson, et al.17 have reported that diester 3 can be readily transformed into hydroxy acetate 4 via this enzymatic process in 98% e.e. and an 80% chemical yield. Similarly, hydroxy acetate 6 was prepared from its parent diester 5 by Pearson, et al.18 in 100% e.e., although 39% yield (50-55% recovered starting material). The enzyme also appears effective on 4-substituted cis-3,5-diacetoxycyclopentenes as Danishefsky19 demonstrated with the conversion of 7 into 8 in 95% yield and 95% e.e. Finally, the successful enantioselective hydrolysis of 9 into 10 (77%, 92% e.e.) extends the range of useful EEAC substrates to acyclic cases.20... 

The 2,6-dimethyl triad of diastereoisomeric esters presents a case similar to the 3,5-dimethyl derivatives. The sole active member is the trans-2,6-dimethyl-eq-4-phenyl chair (examined as acetate ester)(26) and the more active antipode deduced as (28) with equatorial methyl within the front enantiotopic edge (cf. data on /3-2-methyl antipodes). Unlike the (+)-y-3,5-dimethyl isomer (27), structure (28) contains no unfavorable element and its potency is clearly... 

Asymmetric synthesis (1) Use a chiral auxiliary (chiral acetal—the synthetic equivalent of an aldehyde chiral hydrazone—the synthetic equivalent of a ketone) covalently attached to an achiral substrate to control subsequent bond formations. The auxiliary is later disconnected and recovered, if possible. (2) Use a chiral reagent to distinguish between enantiotopic faces or groups (asymmetric induction) to mediate formation of a chiral product. The substrate and reagent combine to form diastereomeric transition states. (3) Use a chiral catalyst to discriminate enantiotopic groups or faces in diastereomeric transition states but only using catalytic amounts of a chiral species. 

Enantiotopically selective ester hydrolysis can also be achieved enzymatically (Table 8). Eiflier one ester group in a me.ro-diester (103)-(1(M>) or one acetate in a me.m-diacetate (107) 111) are saponified with PLE or other lipases. In favorable cases enzymatic acylation and deacylation are stereochemically complementary and may thus be combined to gain access to bodi enantiomers, as illustrated by the example in Table 9. ... 

Intramolecular enantiosituselectivity is exemplified by the biosynthetic formation of the mustard oil glucoside sinigrin (60) in horseradish, " the deprotonation of N-Boc-pyrrolidine (62) with sec-butyllithium (s-BuLi)/(-)-sparteine, followed by methylation, "" and, the oxidation of enol 64. Intermolecular enantiosituselective transformations are exemplified by the hydrolysis of racemic N-dodecanoylphenylalanine p-nitrophenyl esters (( )-67) in the presence of tripeptide catalyst (Z)-L-Phe-L-His-L-Leu (68) in each of the latter two cases, only one (externally) enantiotopic carbonyl reacts preferentially. It should be pointed out parenthetically, that as a result of the enantiosituselectivity in these transformations, one has, in effect, kinetic resolution of ( )-67. The electron-impact induced elimination in acetate 71, and the oxidation of 73 exemplify intramolecular diastereosituselective transformations. The epoxidation of the mixture 76/77 is an example of an intermolecular diastereosituselective process at the same time that each substrate is subject to enantiositunonselectivity of the carbonyl sub-sites. 

Miller developed peptide-based iV-methylimidazole catalysts and applied them to acylative kinetic resolution of N-acylated amino alcohol 29 (Scheme 22.6). The p-hairpin secondary structure of the peptide backbone in catalysts 30 and 31 constitutes a unique environment for effective asymmetric induction. Acylative kinetic resolution of 29 with acetic anhydride in the presence of catalyst 31 proceeded with high s values (s = up to 51). The asymmetric acylation was further extended to remote asymmetric desymmetrisation of a o-symmetric nanometer-scale diol substrate, 32 (Scheme 22.7). Catalyst 33 enabled the enantiotopic hydrojq groups in 32 to be distinguished even though they are located 5.75 A from the prochiral stereogenic centre, and 9.79 A from each other. 

Enantioselective allylic substitution can also be achieved by selective cleavage of one of two enantiotopic leaving groups. Hiis selectivity can occur within a cyclic substrate, as shown in Equation D of Scheme 20.10. Enantioselective allylic substitutions can also occur by replacement of one of two enantiotopic leaving groups on the same carbon, as shown for the acetal structure in Equation E of Scheme 20.10. 

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