Diastereomers catalytic hydrogenation

A reaction that introduces a second chirality center into a starting material that already has one need not produce equal quantities of two possible diastereomers Con sider catalytic hydrogenation of 2 methyl(methylene)cyclohexane As you might expect both CIS and trans 1 2 dimethylcyclohexane are formed... 

Synthesis of the prototype begins with Friedel Crafts acetylation of salicylamide ( ). Bromination of the ketone (25) followed by displacement with amine gives the corresponding ami noketone ( ). Catalytic hydrogenation to the ami noalcohol completes the synthesis of labetolol (24). The presence of two chiral centers at remote positions leads to the two diastereomers being obtained in essentially equal amounts. 

The catalytic hydrogenation of dihydro-1,3-oxazine 118 afforded the tetrahydro-l,3-oxazine derivative 119 as a single diastereomer, in excellent yield. Hydroboration of the double bond in dihydro-1,3-oxazine 120 yielded the acetate 121 as a single regio- and stereoisomer. The configurations of the products indicated that both the hydrogenation of... 

Optical resolution of enantiomeric mixtures which have been obtained by short chemical syntheses continues to be the method of choice for a wide variety of compounds. For instance, the industrial synthesis of (-)-menthol starts from thymol which is catalytically hydrogenated to furnish all four diastereomers in racemic form. 

The synthesis of the C20—C26 fragment started with a 4-alkylation of methyl aceto-acetate The first stereocentre was introduced by enantioselecuve catalytic hydrogenation with Noyort s (S)-binap rhodium complex (cf p 102f.) Stereoselective Frater-Seebach alkylation with allyl bromide introduced the second stereocentre in 90% yield (cf p 27) Stereospecifid introduction of the stereocentres C24 and C2 was achieved by a chelation controlled addition of an allylstannane to an aldehyde (see p 66f) After some experimentation with Lewis acid catalysts and reaction conditions a single diastereomer of the desired configuration was ob-... 

The only concern is die cis stereochemistry of die cycloadduct O. If die planar azomethine ylide adopts the least sterically hindered W geometry, then the cis isomer will be produced as a pair of enantiomers. The use of d.v-stilbenc as the dipolarophile to obtain die all-cis geometry in one step would require that only die endo transition state produces product. Although endo transitions are favored in 1,3 dipolar cycloadditions, mixtures of diastereomers from the exo and endo transition states are usually formed. Catalytic hydrogenation has a higher facial selectivity and is much more likely to give a single diastereomer. 

It is important to note that 5,10-dideaza-5,6,7,8-tetrahydrofolic acid (369) is, as prepared above by catalytic hydrogenation of (388) (followed by saponification), a mixture of two diastereomers (dl and ll). Their separation was achieved by reaction of (369) with ( + )-10-camphorsulphonic acid to give a mixture (ddl and dll) of salts separated by fractional crystallization. Subsequent hydrolysis then gave (369) (isomer A,[a]589 = +31.09) and (isomer B, [a]S89 = -21.06). The initially isolated mixture of diastereomers had [a]s89 = + 10-22. 

Unfortunately, catalytic hydrogenation of24 either on Raney Ni or Pd-C gave an approximately 1 1 mixture of the diastereomers due to the C-5. 

This mixture of diastereomers of 27 was tested in the catalytic hydrogenation of dimethylitaconate and methyl Z-acetamidoacrylate (Scheme 18). The catalytic activity of these complexes is relatively high although lower than that of some of the previously studied purely phosphine based systems, while the enantioselectivity proved to be excellent (ee s between 98 and 99% under optimized conditions). 

A type 2 intramolecular /V-acylnitroso Diels-Alder reaction of hydroxamic acid 177 followed by catalytic hydrogenation of the double bond was employed for the synthesis of substituted bridged bicyclic derivative 178, as a single diastereomer (Scheme 75 <2002OL2637>). Cleavage of the N-O bond was performed by reduction with Na(Hg) amalgam and provided m-3,7-disubstituted azocane 9, as a single isomer in 80% yield. 

The chiral switch of the metolachlor was achieved in 1997. It was put on the market with a content of approximately 90% of the Sc active diastereomers. The key step of the large-scale enantioselective synthesis is the catalytic hydrogenation of the MEA imine shown in Figure 17. A mixture of [IrCl(l,5-cyclooctadiene)]2, the chiral diphosphine (i ,5)-xylyphos, iodide (as tetrabutylammonium or sodium salts) and acetic (30%) or sulfuric (at low... 

The azidochlorination of cyclohexene afforded a mixture of diastereomers (trans/cis 70 30), as shown by further catalytic hydrogenation to 2-chlorocyclohexanamine, IV-benzoylation and comparison of the separated isomers with an authentic sample. However, from steroid-5-enes the /ram-adducts (6/ -azido-5a-chloro) are the most probable products8. 

The enantioselective total synthesis of (-)-hemiasterlin, a marine tripeptide with cytotoxic and antimitotic activity, was achieved by E. Vedejs and co-workers. The asymmetric Strecker reaction was used to construct the key tetramethyltryptophan subunit. The aldehyde substrate was first converted to the corresponding chiral imine with (R)-2-phenylglycinol under scandium triflate catalysis. The addition of tributyltin cyanide resulted in the formation of a-amino nitriles as an 8 1 mixture of diastereomers. Subsequently the cyano group was converted to a primary amide, and the chiral auxiliary was removed under catalytic hydrogenation conditions. 

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