Racemization adducts

Enantioselectivities were found to change sharply depending upon the reaction conditions including catalyst structure, reaction temperature, solvent, and additives. Some representative examples of such selectivity dependence are listed in Scheme 7.42. The thiol adduct was formed with 79% ee (81% yield) when the reaction was catalyzed by the J ,J -DBFOX/Ph aqua nickel(II) complex at room temperature in dichloromethane. Reactions using either the anhydrous complex or the aqua complex with MS 4 A gave a racemic adduct, however, indicating that the aqua complex should be more favored than the anhydrous complex in thiol conjugate additions. Slow addition of thiophenol to the dichloromethane solution of 3-crotonoyl-2-oxazolidinone was ineffective for enantioselectivity. Enantioselectivity was dramatically lowered and reversed to -17% ee in the reaction at -78 °C. A similar tendency was observed in the reactions in diethyl ether and THF. For example, a satisfactory enantioselectivity (80% ee) was observed in the reaction in THF at room temperature, while the selectivity almost disappeared (7% ee) at 0°C. 

Acetylide addition in the racemic version Originally, 4equiv of lithium 2-pyridylacetylide (6) in THF/hexane was added to a mixture of 5 and 4equiv of Mg(OTf)2 in Et20 at room temperature. Precoordination with Mg(OTf)2 and 5 was reported to be essential to prevent reduction of the carbon-nitrogen double bond in 5 [2]. However, it turned out that precoordination was unnecessary for this reaction, as shown in Scheme 1.4, and racemic adduct 7 was obtained in 86% yield by treatment with 1.3 equiv of 6 at -15 °C in THF without Mg(OTf)2. 

Optically active Diels-Alder adducts were also prepared by using a one-pot preparative method and enantioselective formation of inclusion complex with optically active hosts in a water suspension medium.68 For example, A-ethylmaleimide reacts with 2-methyl-1,3-butadiene in water to give the racemic adduct 1. Racemic 1 and the optically active host 2 form enantioselectively a 1 1 inclusion complex of 2 with (+)-l in a water suspension. The inclusion complex can be filtered and heated to release (+)-l with 94% ee (Eq. 12.23). 

When bis-adducts are formed, both syn- and an/i-isomers (from the cyclic dienes) and meso and racemic mixtures (from the acyclic dienes) are detected [e.g. 4, 57, 127, 142], the ratio depending to a large extent on steric factors within the substrate. 1,2-Divinylbenzene reacts with two equivalents of dibromocarbene to give a mixture of the d,l and racemic adducts [106, 124],... 

In their pioneering work. Just and co-workers have described many interesting transformations of the Diels-Alder adducts of furan to methyl nitroacrylate (77 + 77 ) and to dimethyl acetylenedicarboxylate (53). The mixture of racemic adducts 77 + 77 was hydroxylated into the exo-cis-diols 125 + 125 , separable by crystallization. Treatment of the isopropylidene acetal obtained from 125 with diazabicyclo[5.4.0]undec-5-ene (DBU) gave a high yield of alkene 126. Ozonolysis followed by a reductive work-up with dimethylsulfide, then with NaBH4, gave a mixture of epimeric triols 127. Cleavage with sodium periodate afforded 2,5-anhydro-3,4-0-isopropylidene-DL-allose (128) in 15 % yield, based on methyl 2-nitroacrylate used. TTie same allose derivative was obtained from adduct 53. ... 

Comparison of the configuration of the stannane with the prodncts of reaction reveals that primary alkyl halides that are not benzyhc or a to a carbonyl react with inversion at the lithium-bearing carbon atom. In the piperidine series, the best data are for the 3-phenylpropyl compound, which was shown to be >99 1 er. In the pyrrolidine series, the er of the analogous compound indicates 21-22% retention and 78-79% inversion of configuration. Activated alkyl halides such as benzyl bromide and teri-butyl bromoacetate afford racemic adducts. In both the pyrrolidine and piperidine series, most carbonyl electrophiles (i.e. carbon dioxide, dimethyl carbonate, methyl chloroformate, pivaloyl chloride, cyclohexanone, acetone and benzaldehyde) react with virtually complete retention of configuration at the lithium-bearing carbon atom. The only exceptions are benzophenone, which affords racemic adduct, and pivaloyl chloride, which shows some inversion. The inversion observed with pivaloyl chloride may be due to partial racemization of the ketone product during work-up. 

Epoxidation of the racemic adduct 188 with OT-chloroperbenzoic acid (MCPBA) in CH2CI2 proceeded slowly to give the epoxide 189 which further oxidized, usually in acid medium, to ( )rra r-4,5-diol 190 as a diastereoisomeric mixture (70 30) <1997T13783>. Epoxidation of substituted oxazines 28 and 191 with MCPBA led to epoxide esters... 

Evidence for inversion at Ci in the addition of optically active PhCHDCl (192) or PhMeCHBr (141) to [Pd(PPh3)4] has been cited in support of an Sn2 mechanism. However, racemic adducts have been obtained in the... 

Stereoselective aldol condensation. Heathcock and Buse have previously employed 2-methyl-2-trimethylsiloxy-3-pentanone (1) in a highly stereoselective route to 3-hydroxy-2-methylcarboxylic acids (8, 295). Aldol condensation of the lithium enolate derived from 1 with a chiral aldehyde yields ery//iro-aldols, which are cleaved with periodic acid to -hydroxy carboxylic acids. However, when 1 is condensed with a chiral aldehyde such as 2, two eryt/iro-products (3 and 4) are produced. Heathcock and co-workers now report that the 1,2-diastereoselectivity of these aldol condensations can be enhanced by use of the ketone 5. Reaction of racemic 5 with racemic aldehyde 2 furnishes a single (racemic) adduct 6. 

When catalyst 333 was applied in the cycloaddition reaction of 2-methoxy-l,3-butadiene (334) with /-(o-tolyl)maleimide (335), the conesponding cycloadduct 337a was obtained with only 58% ee. However, an ee of 95% was observed when catalyst 338 and N-(o-t-butylphenyl)maleimide (336) were employed (equation 94). The meta methyl substituents on the phenyl groups of catalyst 338 proved crucial for producing 337 with high enantioselectivity. In contrast, the Diels-Alder reaction of maleic anhydride with 2-methoxy-1,3-butadiene using catalyst 338 afforded a racemic adduct. These results were considered to result from a different complexation behavior of the catalyst in the case of maleic anhydride in comparison with, V-arylmaleimides-, ... 

In order to broaden the scope of the amine-catalyzed Michael addition, Yamaguchi examined the system of amine and alkali metal salt [2]. Although amine did not promote the addition of malonate to enones, the LiCl04-Et3N catalyst turned out to be effective. Optically active amines, however, gave racemic adducts. As an extension, the (S)-proline rubidium salt, (S)-21, was developed, which possessed a cation and an amine moiety in the same molecule [2, 22]. The catalyst (S)-21 in chloroform promoted the asymmetric addition of malonate to a wide range of enones and enals as exemplified by the reaction of... 

The optically pure (/ )-indolylamine A was treated with sodium ethylmalonate in refluxing toluene to afford racemic adduct B. Propose a reasonable mechanism for the transformation. ... 

Coupling reactions have also been carried out in a reversal of the imine strategy, by adding a carbanion to an appropriate aldehyde. Thus addition of anion 7.4.21 to acrolein gave racemic adduct 7.4.22 which could be protected, oxidized, and resolved with (+)-ephedrine to give the protected acids 7.4.23 and 7.4.24 (275). 

Alkenes and alkynes undergo cycloaddition reactions with cyclobutadiene produced via decomposition of [Fe(CO)s(cyclobutadiene)]. Further studies on the oxidative decomposition of the optically active complexes (17) and (18) in the presence of dienophiles show that racemic adducts are formed. It would therefore appear that during the addition of the dienophile the iron is not sufficiently close to the cyclobutadiene to maintain the original chiral surroundings of the complex. ... 

Yet another route to the popular Blechert intermediate (—)-402, by Bates and Dewey, started with an unusual conversion of tetrahydrofuian into 4-azidobutan-l-ol (411), which was oxidized to the aldehyde and treated with lithiated trimethylsilylacetylene to give the racemic adduct ( )-412 (Scheme 57). Oxidation to the ketone and reduction with cat-echolborane and the Corey (S)-2-methyl-CBS-oxazaborolidine produced (R)-(- -)-412, but in an ee of only about 75%. A further two steps afforded... 

Condensations of Nonaromatic Dienes. Of bicyclic dienic compounds with a cis-linkage of rings A and B, cis-l-vinyl-9-methyl-A -6-octalone (225) has been studied in the greatest detail. The synthesis of this diene was effected in four stages via the acetylenic carbinol (224) from the methoxyketone (223), obtained in its turn with a yield of about 50% by the diene condensation of 2-methoxybutadiene with 2-methylcyclohex-l-en-3-one [323, 330, 335] (Scheme 21). In the condensation of the dienone (225) with 2,5-dimethylcyclopent-l-en-3-one, eight racemic adducts are theoreti-... 

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