Hydrogenation stereospecific

Highly stereospecific hydrogenations of acetylenes to cis olefins have been achieved also with nickel (P 2) catalysts in the presence of ethylenediamine as prorrtoter (37 8 55 58,72). The catalyst is prepared by reduction of nickel acetate in ethanol with sodium borohydridefi ). Despite successes (44), the use of nickel is relatively infrequent (51). 

The hydrogenolysis proceeds usually with inversion on Pd. This ability of Pd was used for stereospecific hydrogenation of a lactone during the synthesis of a phenyl kainoid on 10% Pd(OH2)/C in AcOEt at 40°C (Scheme 4.44).214... 

Hydrogen-bonding between the 3-oxo group of 1,4,4-trisubstituted pyrrolidine-2,3,5-triones and catalytic amounts of cinchonidine controls the stereospecific hydrogenation of the system over Pt/Al203 to yield chiral 3-hydroxy compounds (-100% yield with ee >60) [21] the nature of the (V-substituent appears to be the controlling factor for the stereoselectivity with PhCH2> Et > n-Bu > cyclo-C6H . 

Fig. 3. Stereospecific hydrogen bond formation of phenyl N-methylcarbamates with acetylcholinesterase 141 (reproduced with permission from Academic Press, Inc.)...

Unsaturated fatty acids may occur as cis or trans isomers trans isomers, which have higher melting points than the corresponding cis isomers, are considered to be nutritionally undesirable. Bovine milk fat contains a low level (5%) of trans fatty acids in comparison with chemically hydrogenated (hardened) vegetable oils, in which the value may be 50% due to non-stereospecific hydrogenation. 

The choice of catalyst applied in the hydrogenation of a certain unsaturated hydrocarbon depends on several factors, such as the reactivity of the substrate and the experimental conditions (pressure, temperature, solvent, liquid- or gas-phase reaction). Multiply unsaturated compounds may require the use of a selective catalyst attaining the reduction of only one multiple bond. The use of suitable selective catalysts and reaction conditions is also necessary to achieve stereospecific hydrogenations. 

Scheme 4. Cis to trans isomerization through stereospecific hydrogen addition (A) and elimination (E) processes on 2MH-site.

Stereospecific hydrogenation of a methylene cyclohexane (2).1 Hydrogenation of 2 with a heterogeneous catalyst results in preferential addition of H2 from the less hindered side to give mainly 4 (R = H). Hydrogenation with the homogeneous... 

The key butenolide needed by Buszek, for his synthesis of (—)-octalactin A, had already been prepared by Godefroi and Chittenden and coworkers some years earlier (Scheme 13.4).9 Their pathway to 10 provides it in excellent overall yield, in three straightforward steps from l-ascorbic acid. The first step entails stereospecific hydrogenation of the double bond to obtain L-gulono-1,4-lactone 13. Reduction occurs exclusively from the sterically less-encumbered ot face of the alkene in this reaction. Tetraol 13 was then converted to the 2,6-dibromide 14 with HBr and acetic anhydride in acetic acid. Selective dehalogenation of 14 with sodium bisulfite finally procured 10. It is likely that the electron-withdrawing effect of the carbonyl in 14 preferentially weakens the adjacent C—Br bond, making this halide more susceptible to reductive elimination under these reaction conditions. 

The silyl-cobalt complex also produced in Eq. (10) is not a catalytic species for hydrosilylation but it is for stereospecific hydrogen exchange60,21°) ... 

Heterocyclic /Lenamino esters were stereospecifically hydrogenated in the presence of Raney Ni, under thermal control. By this method diastereoisomerically pure pyrrolizi-dines and quinolizidines could be prepared178 (Scheme 125). 

The preparation of other stereospecific hydrogenation catalysts such as ruthenium dichloride((S)-(6,6 -dimethoxybiphenyl-2,2 -diyl)bis[bis(3,5-dimethyl-xylene)((R,R)-2-diphenylethylene-diamine)] is provided (2). Other suitable ligands such as l,2-bis(2,5-dimethylphospholano)benzene are described (3). 

Syntheses of new analogues of diphenylpyraline are described. The strategy is flawed by a non-stereospecific hydrogenation. This results in a 50 50 mixture of diastereomers requiring purification by HPLC <03T1403>. 

Acetate incorporation can also be studied by tritium ( H) NMR. It is more sensitive to detection than C and its radioactivity can be used as a simultaneous monitor. A good signal-to-noise ratio has been obtained [25] from as little as 1 mCi of in penicillic acid (3), biosynthesised by Penicillium cyclopium. [ H]-I-Acetate (460 mCi) has been incorporated with 7% efficiency. Chemical shifts and coupling constants are predictable from H spectra and direct information about stereospecific hydrogen labelling can be obtained. 

The first racemic synthesis of fosfomycin is based on the epoxidation of ( ) (Z)-l-propenylphosphonic acid (Scheme 4.24). The reaction was effectively achieved using an excess of H2O2 (30% solution) at 60°C in the presence of Na2WO4 as catalyst (2%) at pH 5.5. The (Z)-l-prope-nylphosphonic acid was prepared by stereospecific hydrogenation, with Lindlar catalyst, of dibutyl 1-propynylphosphonate into dibutyl (Z)-l -propenylphosphonate, followed by hydrolysis of the ester functions with concentrated HCl. The resolution of the racemic ( ) (Z)-l,2-epoxypropylphosphonic acid to fosfomycin was accomplished by way of optically active amines, a-phenylethylamine, or quinine. ... 

Qi) Other Kanamycin Derivatives. Cyclic carbamate derivatives of kanamycin A have been prepared [148], and in another report regiospecific methylation and stereospecific hydrogenation were used to synthesize three kanamycin B analogs with the general formula of compound 302 [149], The same group [150] has also reported conversion of the neosamine ring of kanamycin B to the bicyclo-oxazoctene unit compoimd 303 (part structure). 

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