Diastereomeric mixture

The reduction of a number of thiazolium salts had been shown to yield diastereomeric mixtures of thiazolidines from which it has been possible, in some cases (including that of thiamine), to isolate one pure species (Schemes 94 and 94a). 

Diastereoisomeric Salts. The formation of salts of optically active bases with racemic acids or of optically active acids with racemic bases leads to diastereomeric mixtures which may be resolved by the differential solubiUty of the components of such mixtures (49), ie,... 

Formylation of folate (3) or hydrolysis of 5,10 — CH+ — folate (9) gives (6R,3)-5-formyltetrahydrofohc acid (6) (5-HCO-H folate) (55). On the other hand, (63)-5-HCO-H4 folate is obtained by selective crystaUi2ation in the form of its calcium salt from the diastereomeric mixture of (63, R)-5-HC0-H4 folate (56). 10-Formyltetrahydrofohc acid (7) is a coen2yme in purine synthesis which is synthesi2ed by hydrolysis of 5,10 — CH+ — folate (9) or by hydrogenation of lO-CHO-folate (57). 

Chiral nitrones react with alkenes to produce 3,5-disubstituted isoxazolidines that are nonracemic diastereomeric mixtures and are oriented predominantly cis (equation 53) (77CC303, 79JOC1212). 

Intramolecular electrochemical alkoxylation of racemic l-(3-hydroxybu-tyryl)piperidine afforded a diastereomeric mixture of 2-methylperhydropyr-ido[2,l-Z)][l,3]oxazin-4-ones (OOMIl 1). 

Reaction of 5n,6,7,8,9,l l-hexahydropyrido[2,l-f ][l,3]benzothiazine-7,l 1-dione (47, X = S, R = H) and 2-amino-6-fluorobenzamidine dihydrochloride in boiling EtOH yielded a diastereomeric mixture of spiro derivatives 48 (X = S, R = H), which were separated by flash column chromatography (OOMIPl). 

Irradiation of 9-substituted 6-oxo-3,4-dihydro-2//,6//-pyrido[l,2-Z)]-[1,3]thiazine-4-carboxylate 93 in benzene afforded tricyclic derivatives 94, sometimes as a diastereomeric mixture (00JCS(P1)4373). 

A diastereomeric mixture of l-alkyl-7-(]-alkylperhydropyrido[l,2-u]-pyrimidin-6-yl)-],2,3,4,8,9-hexahydro-9u-pyrido[],2-u]pyrimidines 412 was obtained in the reaction of glutaraldehyde and A-alkyl-1,3-propanediamines in the presence of a drop of AcOH at 0 °C, then at ambient temperature for 13 h (96H(43)2487). 

Treatment of piperidine 116 with yielded a 1 1 diastereomeric mixture of 3-iodomethylperhydropyrido[l,2-c][l,3]oxazin-l-ones 117 (99JOC8402). 

Reaction of tetrahydropyridin-4-one 119 and l,r-carbonyldiimidazole furnished l,3,4,4n,5,6-hexahydropyrido[l,2-c][l,3]oxazine-l,6-dione 120 (99JA2651). Similarly, pyrido[l,2-c][l,3]oxazine-l-one 121 and [1,3] oxazino[4,3-n]isoquinoline-4-one 122 were prepared from the respective 2-(2-hydroxypropyl)piperidine and l-(2-hydroxypropyl)-1,2,3,4-tetrahy-droisoquinoline (99JOC3790). Reaction of a 2 1 diastereomeric mixture of l-(l,2-dihydroxyethyl)-6,7-dihydroxy-l,2,3,4-dihydroisoquinolines 123 and 124 with l,l -carbonyldiimidazole gave a 2.7 1 mixture of 1,9,10-trihy-droxy-l,6,7,ll/)-tetrahydro-2//,4//-[l,3]oxazino[4,3-n]isoquinoline-4-ones 125 and 126, which were separated on preparative TLC plate (99BMC2525). 

Reaction of 40% glioxal with silylated compounds 308 (97SL799, 99SL1094, OOJOC4435) and 310 (97SL799) gave a diastereomeric mixture of l-hydroxy-4-phenylperhydropyrido[2,l-c][l,4]oxazines 309 and 311, respectively. Similarly, diastereomeric mixtures of 8-substituted l-hydroxy-4-phenylperhydropyrido[2,l-c][l,4]oxazines were prepared (01EJOC2385). 

We are the first group to succeed with the highly enantioselective 1,3-dipolar cycloadditions of nitronates [75]. Thus, the reaction of 5,6-dihydro-4H-l,2-oxazine N-oxide as a cyclic nitronate to 3-acryloyl-2-oxazilidinone, at -40 °C in dichloro-methane in the presence of MS 4 A and l ,J -DBFOX/Ph-Ni(II) complexes, gave a diastereomeric mixture of perhydroisoxazolo[2,3-fe][l,2]oxazines as the ring-fused isoxazolidines in high yields. The J ,J -DBFOX/Ph aqua complex prepared from... 

Other important porphyrins which can be derived from hemin are hematoporphyrin (5) and mesoporphyrin (6). Hematoporphyrin (5) which is commercially available at a relatively low price is sensitive towards acid due to the 1-hydroxyethyl groups, so commercial samples contain only 60 to 70% of hematoporphyrin. Pure hematoporphyrin dimethyl ester which is a racemic and diastereomeric mixture of four stereoisomers can be obtained by esterification with diazomethane and subsequent chromatography on neutral alumina.84 The pure stereoisomers can be prepared by enantioselective reduction of diacetyldeuteroporphyrin dimethyl ester.85a b The... 

Cyclopropane-fused chlorins are formed in good yields from copper porphyrins with ethyl diazoacetatc in benzene in the presence of copper(I) iodide.200,21 In the case of copper oc-taethylporphyrin 10, which gives a diastereomeric mixture of cyclopropane adducts 11, ethyl me o-porphyrincarboxylate 12 and a geminally dialkylated chlorin 13 (a rearrangement product of the cyclopropane chlorin 11) are observed as minor byproducts.200... 

Hematoporphyrin dimethyl ester (15, 1.52 g, 2.43 mmol) (diastereomeric mixture) and Af.At-dimethyl-acetamide dimethyl acetal (8 mL) were suspended in o-xylcnc (100 mL), degassed and then heated with exclusion of light in a flask equipped with a reflux condenser and a Soxhlet apparatus containing 3 A molecular sieves. The temperature was raised during 15 min from rt to 115 C and kept at this temperature for 30 min. Then the temperature was raised to 155 C and the mixture kept at this temperature for 3 h. The mixture was evaporated in a bulb tube and the residue subjected to column chromatography [silica gel (ICN), CH2Cl2/MeOAc/MeOH 10 5 0.5] with exclusion of light yield of pure 16A 305 mg (17 %) yield of pure 16B, 375 mg (20%) and 187 mg (10%) of a mixture of 16 A and B. 

A related palladium(O)-catalyzed epimerization of y-aziridinyl-a,P-enoates 244 was also reported by Ibuka, Ohno, Fujii, and coworkers (Scheme 2.60) [43]. Treatment of either isomer of 244 with a catalytic amount of Pd(PPh3)4 in THF yielded an equilibrated mixture in which the isomer 246 with the desired configuration predominated (246 other isomers = 85 15 to 94 6). In most cases the isomer 246 could be easily separated from the diastereomeric mixture by a simple recrystallization, and the organocopper-mediated ring-opening reaction of 246 directly afforded L,L-type (E)-alkene dipeptide isosteres 243. 

Cleavage of the oxathiane moiety can be carried out with iV-chlorosuccinimide/silver nitrate and leads to the a-hydroxy aldehyde 21 along with a diastereomeric mixture of sultines 20. The sultines can be reduced to the hydroxy thiol 22 which can be reconverted to the chiral auxiliary 16 in ail overall recovery of about 70%39. 

Complex ( + )-(FeS)-3 is obtained by extraction of the diastereomeric mixture with 50 mL of pentane in portions at r.t. The specific rotation of the solid product obtained from the first fraction is [a]jJ6 +50 (o = 0.001. benzene). The rotation of the remaining mixture becomes more negative as the (+)-isomer is removed. After concentration of the combined fractions, the resulting material, enriched in the ( + )-isomcr, is further purified by extraction with 10 mL of pentane in portions. Repetition of the pentane extraction procedure affords ( + )-(FeS)-3 yield-. 750 mg (30%) mp 120"C (dee) [a] +72 (c = 0.001, benzene). The residue, enriched in (—)-(FeR)-3 is extracted for 1 h with boiling pentane. After separation from the extraction liquor, a yellow-orange solid is obtained yield I -35 g (50%) mp 120°C (dec) — 120... 

From the corresponding diastereomeric mixture (15 1.5 1), obtained by the addition of methyl 3-nitropropanoate to (.S )-2-(bcnzyloxy)propanal, the (/(/C4/(,5,Y)-isomer 15 was obtained after debenzylation and ketalization13. , Al 0... 

Intermolecular reaction of the mannose-derived 2,3-0-isopropylideiie-a-D-/y.vc>-pentodialdo-l,4-furanoside 13 affords a diastereomeric mixture of nitroalcohols 14. Upon fluoride-catalyzed desilylation, a stereoisomerically pure nitrocyclitol 15 was obtained from a successive intramolecular nitroaldol reaction as a consequence of the reversibility of the nitroaldol reaction which, in this case, allows the equilibration of isomers through open-chain intermediates33. 

Treatment of the optically active formaldehyde dithioacetal monoxide with ethyl benzoate in the presence of sodium hydride gives the benzoylated product as a diastereomeric mixture in a thermodynamically controlled (65 35) ratio66. 

The main product is the /-product which is obtained as a 2 1 diastereomeric mixture whereas the a-product is formed as a mixture of all four possible diastereomers. Subsequent experiments confirmed that thermodynamic reasons are responsible for the preferential formation of the /-product and for the absence of the Z-isomer in this reaction. 

When chloromethylsulfinylmethane is reacted with unsymmetrical ketones in the presence of potassium rm-butoxide in fert-butanol, diastereomeric mixtures of oxiranes are formed, showing that the asymmetric induction at the prostereogenic carbonyl carbon atom is low21. 

Application of the same methodology to thiophenecarbaldehydes results in the formation of diastereomeric mixtures of the corresponding thienylglycinonitriles53. 

Although the (/ )-diastercomer is the minor component, as directly determined by HPLC it crystallizes from the solution of the diastereomeric mixture of the JV-galactosyl-tm-leucinonitriles63. 

An analogous Lewis acid catalyzed cyclization of the oi-acctoxy derivatives 3 gives rise to one pair of diastereomers of 4 in the case of the ( )-alkenc, while the (Z)-alkene affords a diastereomeric mixture of (2S, 3/J, 4/J )-4 (major product) and (2,S, 3,S, 4/ )-4 (minor product)90. 

The addition of the anions of racemic 1-(diphenyl)- and l-(diethoxyphosphinyl)-2-butenes to 2-cyclopentenone or 2-cyclohexenone gives y-l,4-add ucls. () A1 ly 1 systems give exclusively. vy/t-adducts while (Z)-allyl systems give exclusively //-adducts. 2-Cycloheptenone gives diastereomeric mixtures of 1,4-adducts and 1,2-addition products1. 

Optically pure (S)-benzyl methyl sulfoxide 139 can be converted to the corresponding a-lithio-derivative, which upon reaction with acetone gave a diastereomeric mixture (15 1) of the /S-hydroxysulfoxide 140. This addition reaction gave preferentially the product in which the configuration of the original carbanion is maintained. By this reaction, an optically active epoxy compound 142 was prepared from the cyclohexanone adduct 141181. Johnson and Schroeck188,189 succeeded in obtaining optically active styrene oxide by recrystallization of the condensation product of (+ )-(S)-n-butyl methyl sulfoxide 143 with benzaldehyde. 

All the y-sultines were obtained as diastereomeric mixtures (ca 1 1, by NMR), and each one of y-sultines ( + )-49 and ( + )-51 (R = t-Bu) was separated into two diastereomers A and B by column chromatography. The oxidation of y-sultines (— )-49A and (+ )-49B to the corresponding optically active sultones (+ )-52A,B, which lack a chiral sulfur, may be taken as proof that the observed optical activity in the sultines is also due to the y-carbon. This result seems to exclude the intermediacy of vinylsulfene in the reaction mechanism, since its disrotatory closure would lead to racemic y-carbon in the product. 

The intramolecular cycloaddition has proven to be the method of choice for the preparation of steroids. A diastereomeric mixture of 204, prepared from 191 and tosylate 203 has been cleanly converted to dl-estra-1,3,5(10)-trien-17-one (205) in 85% yield (equation 130). A second example of the intramolecular cycloaddition reaction is the formation of the cycloadduct (209), the key intermediate in a synthesis of the As-pidosperma alkaloid aspidospermine, upon heating 208 at 600 °C (equation 131)124. The sulfone 208 can be prepared by reaction of 3-ethyl-3,4,5,6-tetrahydropyridine (206) with the acid chloride 207. 

Pentenomycin (33), a highly oxygenated cyclopentenoid with a quaternary chiral center (Scheme 6), was prepared by a similar reaction sequence [29]. The RCM precursor 31 was prepared in eight steps from D-mannose via iodo compound 29 and aldehyde 30 (1 1 diastereomeric mixture). RCM of 31 led to the epimeric cyclopentenols 32. 

RCM of a dienyne was also a key step in Mori s recent total synthesis of the alkaloid erythrocarine (447) [183]. The tetracyclic framework of447 was elaborated in the penultimate step, by exposing the hydrochloride of metathesis precursor 445 (1 1 diastereomeric mixture at the carbinol center) to first-generation catalyst A. The tandem process occurred smoothly within 18 h at room temperature leading to tetracycles 446 (1 1 mixture) in quantitative yield. Deprotection of the a-acetoxy isomer 446a led to 447 (Scheme 88). 

In the presence of 1 equiv. of chlorotrimethylsilane, the transformation can be performed with substoichiometric amounts of titanium tetraisopropoxide (25 mol%) to yield 73% of the diastereomeric mixture of the corresponding, V,, V-d i al ky 1 am inocyclopropanc.7... 

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