Pyrrolidines reaction with benzaldehyde

Chiral enamine derivatives have also been used as electron-rich alkenes. The oxazoline derivative 17 reacted with benzaldehyde to yield the two stereoiso-meric oxetanes 18a and 18b with a diastereomeric excess of 67% (Scheme 5) [12]. A significantly higher diastereoselectivity was observed in the case of the reaction of the pyrrolidine derivatives 19 where the enamine function is localized inside the five membered ring [13]. Then the oxetane 20a (R — n-Cgil g) was used in an asymmetric synthesis of the antifungal alkaloid (+ )-preussin. The approach of the 3n,7T excited ketone preferentially occurred syn with respect to... 

Asymmetric synthesis of 1,2-diol derivatives based on asymmetric aldol reactions of a-alkoxy silyl enol ethers with aldehydes has been developed. The reaction of (Z)-2-benzyloxy-l-(5)-ethyl-l-trimethylsiloxyethene with benzaldehyde was conducted in dichloromethane at -78 °C with a chiral promoter consisting of Sn(OTf)2, (5)-l-ethyl-2-[(piperidin-l-yl)methyl]pyrrolidine, and Bu2Sn(OAc)2, to afford the corresponding aldol adduct in 83 % yield with 99 % anti preference. The enantiomeric excess of anti aldol is 96 % [38a]. In the aldol reaction of several kinds of aldehydes, e.g. aromatic,... 

Kinastowski, S., Mroczyk, W. The mechanism of the Knoevenagei reaction of malonic ester with benzaldehyde, catalyzed by pyrrolidine. 

The ligands 2b-g were also employed for the reaction of butyllilhium with benzaldehyde, and it was observed that formation of alcohol with R configuration is preferred when ligands with larger substituents, R and R, were employed (see Table 7). In addition, it is noteworthy that (R)-l-phenyl-l-pentanol is obtained in 68% e.e. by employing the chiral ligand 5 which has three pyrrolidine moieties (entry 15)... 

Wilkinson s catalyst mediates a Cannizzaro-like process with benzaldehyde in ethanol the aldehyde serves as a dihydrogen source to reduce itself, and the benzoic acid formed is esterified by the solvent (eq 8). Pyrrolidine is IV-methylated by methanol in the presence of RhCl(PPh3)3, a reaction that presumably occurs via hydrogen transfer from methanol, condensation of the formaldehyde formed with pyrrolidine, then hydrogen transfer to the iminium intermediate (eq 9). ... 

Chromium (and tungsten) imino carbene complexes 113 are found to be synthetic equivalents for nitrile ylides on the basis of the resonance structure (Scheme 5.23) [34]. The reaction of the imino carbene complex 113 with alkyne 114 affords pyrrole 115. Imidazoles 116 and 120, pyrrolidines 118, and oxazoline 119 are also obtained by the [3+2] cycloaddition of the imino carbene complexes 113 with benzonitrile, alkenes 117, and benzaldehyde, respectively. Although the regiochemical outcome of these reactions is unpredictable, the regioselectivity can be correlated with the resonance structure in the case of the reaction with 3-hexyn-2-one. 

Liskamp has reported the synthesis and the screening in asymmetric catalysis of a library of polymer-supported peptidosulfonamide [147]. Rt) or (5 -pyrrolydines 222 prepared in six steps from D or Z-tartaric acid were anchored onto Argonaut resin (0.41 mmol/g) to afford the corresponding supported pyrrolidines 223 (Scheme 91). The polymeric peptidosulfonamides 224 and 225 were then synthesized in four steps from the immobilized pyrrolidines 223. The different chiral polymers were tested in the titanium-mediated diethylzinc addition to benzaldehyde,/ -chlorobenzaldehyde, cyclohexanecarboxaldehyde and phenylacetaldehyde. Both yield and ee were very low with all these supported-ligands for the enantioselective reaction with the two aliphatic aldehydes. With aromatic aldehydes, the best results were observed with both leucine-derived supported peptidosulfonamides 224d and 225d. 

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. 

The tandem reaction of carbenoids with simple imines to form azomethine ylides which then undergo 1,3-dipolar cycloaddition with various dipolarophiles was first reported in 1972.81 Treatment of phenyldiazomethane with copper bronze in the presence of excess N-benzylidenemethylamine resulted in the isolation of imidazoline 170. Formation of this product was rationalized by carbenoid addition onto the imine nitrogen to give azomethine ylide 169 which then underwent a 1,3-dipolar cycloaddition with another molecule of imine to produce the observed product. Bartnik and Mloston subsequently extended this observation by using other dipolarophiles.82 For example, catalytic decomposition of phenyldiazomethane and A-benzylidenemethylamine in the presence of dimethyl maleate or benzaldehyde gave pyrrolidine 171... 

Oxidations with peroxybenzoic acid are carried out in solutions in dichloromethane, chloroform, benzene, ether, or ethyl acetate at or below room temperature and include epoxidation of double bonds [295, 296, 297, 298, 299, 300, 301], oxidation of benzaldehydes to carboxylic acids or phenols [302], the Baeyer-Villiger reaction of ketones [303, 304, 305, 306, 307], and oxidation of sulfides to sulfoxides [308, 309]. Peroxybenzoic acid is also used for the anti hydroxylation of double bonds [310], the oxidation of pyrrolidines to pyrrolidones [377] and of pyrroles to succinimides [377], and the preparation of azoxy compounds from azo compounds [372]. 

Readily available chiral amines related to the Betti base [phenyl(2-hydroxy-l-naphthyl)methanamine] catalyse enantioselective addition of diethylzinc to aldehydes in moderate to excellent ee Observed enantioselectivities in addition of diethylzinc to aldehydes catalysed by a series of (5)-proline-derived pyrrolidines have been explained in terms of steric effects. New 2,5-diazabicyclo[2.2.1]heptanes have been applied to enantioselective addition of diethylzinc to benzaldehyde. (S)-2-(3-Methyl-2-pyridyl)-3,5-di-r-butylphenol (76) has been used as an enantioselective catalyst of diethylzinc addition to benzaldehydes. Reaction in toluene shows a significant variation in % ee with temperature, including observation of an inversion temperature with maximum ee. This value varies with the nature of the para-substituent in the aldehyde, and the overall behaviour may be due to a shift in the rate-determining step of the reaction. Other reports of zinc reagents include enantioselective addition of diethylzinc to aldehydes addition of diphenylzinc to aldehydes using a chiral ferrocene-based hydroxyoxazoline catalyst in up to 96% ee and 3-exo-morpholinoisoborneol has been proposed as a more convenient and efficient enantioselective catalyst of alkylzincs than Noyori s original 3-exo-dimethylamino catalyst. ... 

Ort/io-substituted benzaldehyde complexes have been prepared in high enantiomeric purity (97% ee), and in a one-pot sequence, from an optically pure hydrazone derivative, readily available from -q -benzaldehyde chromium tricarbonyl and SAMP [(S)-l-amino-2-(methoxymethyl)pyrrolidine]. The novelty derives from the combined use of a diastereoselective orthoaddition reaction of an organolithium nucleophile and a hydride abstraction with a triphenylmethyl cation. The subsequent acid hydrolysis serves to remove the hydrazone group, thus liberating the aldehyde functionality (Scheme 6.13). 

Dibutyltindiacetate (0.44 mmol) was added at room temperature to a solution of tin(II) triflate (0.4 mmol) and (S)-l-ethyl-2-[(piperidin-l-yl)methyl]-pyrrolidine 84 (0.48 mmol) in dichloromethane (1 mL). The mixture was stirred for 30 min then cooled to —78 °C. Dichloromethane solutions (0.5 mL) of the silyl enol ether of S-ethyl 2-benzyloxyethanethioate 82 (0.4 mmol) and benzaldehyde (0.27 mmol) were added successively. The reaction mixture was further stirred for 20 h then quenched with aqueous NaHC03. After the usual work up the desired aldol adduct 90 was obtained in 83% yield (syn/anti = 1 99, 96% ee anti)). 

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