Mixture of epimers

The presence of an a-bromo substituent may cause anomalies. With NaBH4, 2a-bromo-5a-cholestan-3-one gives a mixture of epimers, in which the 3p-o predominates. 4 -Bromo-17)5-hydroxy-5)5-androstan-3-one acetate gives 25% of the 315,4 -bromohydrin and 34% of the 3a,4)5-compound. Reduction of 7a-bromo-3)5,5a-diacetoxycholestan-6-one gives exclusively 7a-bromocholestane-3)5,5a,6a-triol 3,5-diacetate,whereas reduc-... 

Crude tetrahydropyranyl ethers are usually a mixture of epimers due to formation of an additional asymmetric center. Consequently these derivatives are sometimes difficult to characterize. 

The intramolecular cycloaddition reaction of enamides has been exploited in alkaloid synthesis (81JOC3763). One successful application is provided by the total synthesis of the fused indolizidine 5 from 4 as a 1 1 mixture of epimers in 43% total yield 5 is a key intermediate in aspidosperma alkaloid synthesis (79JA3294). 

R1 =C,H5 rms-5-benzyloxymethyl-4,5-dihydro-4-(l-hydroxypropy[)-3-methylisoxazole yield 30% (50% recovered starting material) 2 1 mixture of epimers at C-1. ... 

Similarly, the oxazoHdine (it,S)-147, obtained as a mixture of epimers at C2 from N,N-dibenzyl (it)-phenylalaninal and hl-benzyl (S)-valinol, reacted with Grignard reagents to form in situ the iminium ion 148, from which the diamino alcohols 149 were produced as a single diastereomer [71 ] (Scheme 23). On the other hand, when the oxazoHdine derived from the (S)-aldehyde was used, the diamino alcohol was obtained as a 70 30 mixture of diastereomers. Alhough the preparation of the primary 1,2-diamines was not explored in that paper, compoimds 149 would be the precursors of the syn 1,2-diamine... 

In the presence of TMSOTf 20 the olefin 1266 adds methyl benzene sulfenate to give the episulfonium triflate 1267, which cyclizes in 97% yield to give a ca 1 1 mixture of epimers of 1268 [57] (Scheme 8.23). 

Entries 8 to 15 are examples of intramolecular reactions. Entry 8 involves two unactivated double bonds and was carried out at a temperature of 280°C. The product was a mixture of epimers at the ester site but the methyl group and cyclohexenyl double bond are cis, which indicates that the reaction occurred entirely through an endo TS. 

The A-D-ring analog 30a,b (mixture of epimers) has been prepared from the epoxide 3a,b by base catalyzed epoxide cleavage, hydroxymethylenation, and O-alkylation of the butenolide unit using standard conditions. Hydroxymethylenation of keto-ester 7 followed by butenolide addition provided the A-D-ring analog 31. 

Decarboxylation of 16 using the previously described NMP, lithium chloride method provided the dione 32. Selective reduction of the least hindered carbonyl was readily effected using sodium borohydride providing 33. Hydroxymethylenation followed by O-alkylation of the butenolide unit by standard procedures provided the A-B-D-ring analog 34a,b (racemic mixture of epimers). 

The high levels of, sy -diastereoselectivity suggest aldolization through a closed Zimmerman-Traxler-type transition structure via intermediacy of the Z-enolate. When the transformation is performed using PhSiDj, a single deuterium is incorporated at the /3-position of the product as an equimolar mixture of epimers, inferring rapid isomerization of the kinetically formed cobalt enolate prior to cyclization or reversible aldol addition. The stereochemistry of the deuterated product was established by single crystal neutron diffraction analysis (Scheme 44). 

A)-Ketorolac 132, a nonsteroidal anti-inflammatory dmg (NSAID), was synthesized in a two-step procedure based on an intramolecular oxidative coupling of pyrrole at the C-2 position with a chiral sultam enolate 130 leading to dihydropyrrolizine 131 as a 4.5 1 mixture of epimers (Scheme 23). Subsequent benzoylation, performed on the crude... 

Polyhydroxylated indolizidines have attracted considerable interest due to their potent activity as glycosidase inhibitors. Some analogues of these molecules bearing a sulfur instead of a carbon atom at the anomeric position such as 430-432 have been prepared (Scheme 112). Compound 431 was shown to give a 3/7 mixture of epimers at the anomeric position in DzO. 

Indolin-3-yl)ethyl]aminomethylenemalonates (27) were treated with a 3 2 mixture of acetic anhydride and acetic acid at reflux for 72 hr to give aspidosperma alkaloids (1418) in 45-92% yields, as a mixture of epimers (Scheme 56) (77H1699, 77MI3 78CC943 79MI1). 

Reaction of pure (5ir,/ c)-9 with nitrones IV or V followed by the addition of an excess of n-Bu4NBr (Scheme 21) gives the corresponding 3,5-crt(io-isoxazolidines in quantitative yield. Table 5 collects the ee values obtained for the two nitrones. Comparison of the results of Table 5 with those of Table 4 indicates that, whereas a mixture of epimers complex 9 (67% / ir,/ c/33% 5ir,/ c, molar ratio) reacts with nitrones 2,3,4,5-tetrahydropyridine /V-oxide (IV) or 3,4-dihydroisoquinoline... 

Substituted malonates and (5-keto-esters have also been successfully used as pronucleophiles (Scheme 9.11) [25a, 36]. From P-ketoesters, approximately 1 1 mixtures of epimers are generally formed. Products derived from 2-alkenylmalo-nates have been subjected to Ru-catalyzed ring-closing metathesis to give cyclo-pentene derivatives in good yield [25a, 36]. With the ester-amide displayed in Scheme 9.11 as pronucleophile, 1 1 mixtures of epimers were also formed [44]. 

Commercially available ethyl nitroacetate is an interesting pronucleophile, because it can serve as the synthetic equivalent of either nitromethane or glycine. The ethoxycarbonyl group can also be considered as a protecting group against dialkylation. The allylic alkylation with ethyl nitroacetate did not require an additional base (salt-free conditions). As a consequence of the high acidity of the chirality center a to N, 1 1 mixtures of epimers were formed. 

MOM ethers provided compound 78 as a 1 1 mixture of epimers at the ben-zylic carbon. These epimers were separable by chromatography and the subsequent reactions were carried out with either of the separated isomers (the yields shown in Scheme 17 are average yields for the transformations of... 

An intermolecular Diels-Alder reaction of the A-sulfinyl diene 116, prepared from amino diene 115, gave a 1 2 mixture of epimers of 1-... 

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