Hydrogenation stereoselective synthesis

During the stereoselective synthesis of azetidin-2-ones the reaction with 1 atm hydrogen over 10% Pd/C hydrogenated the double bond and hydrogeno-lyzed the benzyl group (Scheme 4.37).173... 

Synthetic transformations of the products of the intramolecular bis-silylation have been examined. The five-membered ring products derived from homopropargylic alcohols were hydrogenated in a stereoselective manner (Scheme ll).90 Oxidation of the products under the Tamao oxidation conditions (H202/F /base)96 leads to the stereoselective synthesis of 1,2,4-triols. This method can be complementary to the one involving intramolecular bis-silylation of homoallylic alcohols (vide infra). 

There is little doubt that the hydrogenation of dehydro a-amino acids is the best-studied enantioselective catalytic reaction. This was initiated by the successful development of the L-dopa process by Knowles (see below) and for many years, acetylated aminocinnamic acid derivatives were the model substrates to test most newly developed ligands. As can be seen below, this is the transformation most often used for the stereoselective synthesis of a variety of pharma and... 

Several catalysts are used in the field of microbial reductions. The common features of these catalysts are the high selectivity and their use only on a laboratorial scale. They are applied, for example, in the stereoselective synthesis of pharmaceutical intermediates. The reductions are exclusively selective either in the hydrogenation of the C=C double bond or in that of other reducible groups. One of the most widely used catalysts is baker s yeast. In the following hydrogenations, which are catalyzed by Saccharomyces cerevisiae, high enantioselectivities were achieved (equations 35-38)105-108. 

The stereoselective synthesis of tetrahydronaphthalenones was carried out via homogeneous hydrogenation. The reduction at 2 bar hydrogen pressure gave the saturated product in good yield (equation 69)165. 

In addition, stereoselective synthesis of solenopsin A has been reported by four research groups. An approach utilizing the stereoselective reductive de-cyanation (596) starts with aminonitrile 229, prepared from 2-picoline. It was selectively hydrogenated in the presence of Pd-C, followed by alkylation with undecyl bromide, affording 231. Reductive decyanation of 231 with NaBH4 in MeOH led to predominant (8 2) formation of the trans isomer (232) which was then debenzylated to ( )-solenopsin A (Id). The cis product (Ic) was in turn prepared by treatment of 231 with sodium in liquid ammonia followed by de-benzylation (Scheme 10). 

The aim of this article is to focus on the diversity of aldonolactones as chiral synthons. The chemistry of aldonolactones was an almost unexplored area when, in 1979, we started our investigations on the reaction of aldonolactones with hydrogen bromide in acetic acid thereby obtaining bromodeoxyaldonolac-tones [1,2]. These compounds have over the years proven to be very versatile compounds for stereoselective synthesis, both in the carbohydrate field, giving access to otherwise less readily obtainable sugars, and as chiral, optically pure synthons in a broader sense within organic chemistry. 

The other stereoselective synthesis/281 shown in Scheme 8, foresees conversion of Boc-L-Asp-OtBu 20 into the related (3-aldehyde 22 via the Weinreb amide 21 and its reduction with diisobutylaluminum hydride (DIBAL-H). Wittig condensation of 22 with the ylide derived from (3-carboxypropyl)triphenylphosphonium bromide using lithium hexamethyldisilaza-nide at —78 to 0°C, produces the unsaturated compound 23 which is catalytically hydrogenated to the protected L-a-aminosuberic acid derivative 24. Conversion of the co-carboxy group into the 9-fluorenylmethyl ester, followed by TFA treatment and reprotection of the M -amino group affords Boc-L-Asu(OFm)-OH (25). 

Furo[3,4-7]pyridines can be prepared in a stereoselective synthesis involving a ruthenium-catalyzed asymmetric transfer hydrogenation reaction <2001TL1899>. The reaction proceeds with exceptionally high yield and ee (Equation 50). 

It has recently been demonstrated that a stereoselective synthesis of dipeptides by hydrogenation of the corresponding monodehydropeptides (N-protected free acids or methyl esters) is possible. In this reaction, chiral catalysts, for example BPPM (13), in the form of a Wilkinson complex have been used. These are superior to the corresponding DIOP complexes (DIOP = P,P -[2,2-dimethyl-l,3-dioxolane-4,5-bis(methylene)]bis(diphenylphosphane). A d.s. value of 90—99% was generally obtained 49 ... 

A new stereoselective synthesis of 1,2,3-trisubstituted cyclopentanes based on the Wag-ner-Meerwein rearrangement of a 7-oxabicyclo[2.2.1]heptyl 2-cation starts with the Diels-Alder product of maleic anhydride and a furan (78TL2165, 79TL1691). The cycloadduct was hydrogenated and subjected to methanolysis. The half acid ester (47) was then electrolyzed at 0 °C to generate a cationic intermediate via the abnormal Kolbe reaction (Hofer-Moest reaction). Work-up under the usual conditions provided the 2-oxabicyclo[2.2.1]heptane (48) in 83% yield. Treatment of this compound in turn with perchloric acid effected hydrolysis of the ketal with formation of the trisubstituted cyclopentane (49) in nearly quantitative yield (Scheme 11). Cyclopentanes available from this route constitute useful... 

SCHEME 71. Stereoselective synthesis of a carbapenem intermediate by BINAP-Ru-catalyzed hydrogenation. 

Dynamic Resolution of Chirally Labile Racemic Compounds. In ordinary kinetic resolution processes, however, the maximum yield of one enantiomer is 50%, and the ee value is affected by the extent of conversion. On the other hand, racemic compounds with a chirally labile stereogenic center may, under certain conditions, be converted to one major stereoisomer, for which the chemical yield may be 100% and the ee independent of conversion. As shown in Scheme 62, asymmetric hydrogenation of 2-substituted 3-oxo carboxylic esters provides the opportunity to produce one stereoisomer among four possible isomers in a diastereoselective and enantioselective manner. To accomplish this ideal second-order stereoselective synthesis, three conditions must be satisfied (1) racemization of the ketonic substrates must be sufficiently fast with respect to hydrogenation, (2) stereochemical control by chiral metal catalysts must be efficient, and (3) the C(2) stereogenic center must clearly differentiate between the syn and anti transition states. Systematic study has revealed that the efficiency of the dynamic kinetic resolution in the BINAP-Ru(H)-catalyzed hydrogenation is markedly influenced by the structures of the substrates and the reaction conditions, including choice of solvents. 

Now, both the utility and the versatility of our method are demonstrated in the stereoselective synthesis of natural (+)-valienamine (25) and (+)-validamine (29) (7/) (Scheme 3). Furthermore, the anchor effect of an amino group will be described in the stereoselective hydrogenation of the olefin of25 to give 29 (Fig. 1). 

U. Kazmaier, J. M. Brown, A. Pfaltz, P. K. Matzinger, H. G. W. Leuenberger, Formation of C-H Bonds by Reduction of Olefinic Double Bonds Hydrogenation, in Methoden Org. Chem. (Houben-Weyl) 4th ed. 1952-, Stereoselective Synthesis (G. Helmchen, R. W. Hoffmann, J. Mulzer, E. Schaumann, Eds.), Vol. E21d, 4239, Georg Thieme Verlag, Stuttgart, 1995. 

Carless, H.A.J., Swan, D.I.,and Haywood, D.J. (1993) Stereoselective synthesis of tetrahydrofuran-3-ols by photochemical 8-hydrogen abstraction of (3-allyloxy-carbonyl compounds. Tetrahedron, 49, 1665-1674. 

Although carbohydrates are cheap and readily available chiral compounds, their application in stereoselective synthesis was for a long time limited to ex-chiral-pool syntheses [3]. They have been considered too complex compared to other chiral auxiliaries, for example a-pinene in borane-chemistry [4] or BINAP-derivatives in reduction chemistry [5]. However, it has been shown during the past few years that carbohydrates can be successfully applied as stereodifferentiating tools in many different reaction types such as aldol- [6], hydrogenation- [7], carbonyl addition- [8], Michael- [9], Diels-Alder- [10], hetero-Diels-Alder [11], and rearrangement reactions [12]. 

A stereoselective synthesis of ( )-ephedrine and ( )-methylephedrine has been described (318). The method utilizes a carbanion, in which the negative charge is located a to the nitrogen, formed by deprotonation of 1. Subsequent reaction with benzaldehyde yields the 2-oxazolidone 2, and thermal removal of the diphenylphosphinyl group gives the 2-oxazolone 3. Hydrogenation of 3 proceeds with perfect stereoselectivity to yield the erythro isomer 4, which is easily converted to ( )-ephedrine or ( )-W-methylephedrine. 

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