Stereospecificity hydride

Stereorigid radical cations may undergo stereospecific sigmatropic shifts for example, the puckered ions, anti- and syn- 5-methyl-19 ", undergo stereospecific hydride or methyl migration, respectively, forming the 1-methylcyclopentene ion (46 ) and the 3-methyl isomer (47 ). ... 

Complex rearrangements involving both the steroid backbone and the cholestane side chain were observed when either the Westphalen diacetate (252) or 5a-cholestane-2a,5-diol (253) was treated with HF at —60 °C. The 25-fluoro-product (254) was isolated in low yield from the 2,5-diol, and an analogous product resulted from the Westphalen diacetate. Inversion of the configuration at C-20 to give the unnatural (20S)-isomer is thought to involve stereospecific hydride transfer from C-25 to a C-20 carbocation subsequent nucleophilic attack at C-25 gives the 25-fluoro-compound. A hydride transfer from C-20 to C-13 is postulated to account for... 

A curious reaction was observed when epoxy derivatives of certain exo-methylene groups e.g. i) were treated with BFs or perchloric acid [34,35]. The products are believed to be five-membered cycHc ethers 2.). The exact mechanism of the ring expansion process is uncertain, but it has been represented as epoxide cleavage concerted with two stereospecific hydride... 

Allylic epoxides seem to behave normally. Stereospecific hydride migrations were observed in the McMurry et al. synthesis of eremophilone. Treatment of the isomeric epoxides (268) and (270) under standard conditions resulted in the exclusive formation of the rearranged ketones, as illustrated in equations (114) and (115). 

Dehydrogenases, reductases and a number of other enzymes, such as UDP-glucose epimerase, utilize NAD or NADP as an enzymatic cofactor and catalyze the oxidation/reduction of various substrates, facilitating the usually reversible stereospecific hydride transfer from the C4 position of the 1,4 dihydronicotinamide ring of NAD(P)H to substrate. The reaction catalyzed by lactate dehydrogenase and a schematic drawing of the putative hydride transfer reaction that takes place are shown in Fig. 15.1. 

These results indicated that the Wagner-Meerwein-type rearrangement was followed by a stereospecific hydride transfer from C-18a to C-13a which led to an immonium ion, the latter finally being reduced to derivative (11) (Scheme 1). Inversion at position 12, as expected for a Wagner-Meerwein-type rearrangement, is in accordance with the generality of the c-nor-D-homo rearrangement. 

Under kilo-electron-volt energy range CID, hydride transfers are usually occurring during stereospecific dissociations of deprotonated molecules. These take place typically from deprotonated monovalent -X functions [essentially, primary and secondary alcohols and thiols, Eqs. (17.4a, b)]. Early examples concern first a stereospecific hydride transfer from a secondary alkoxide site of 7ra j -1,4-cyclohexanediol anion to the opposite hydroxy group (Scheme 17.13) to eliminate H2. From the cis isomer, the process is different... 

Tabet, J. C. Hanna, I. Feuzon, M. Stereospecific hydride transfer under NCI/hydroxide ion conditions. 2—Origins of the C2H4O elimination from... 

Alkenes in (alkene)dicarbonyl(T -cyclopentadienyl)iron(l+) cations react with carbon nucleophiles to form new C —C bonds (M. Rosenblum, 1974 A.J. Pearson, 1987). Tricarbon-yi(ri -cycIohexadienyI)iron(l-h) cations, prepared from the T] -l,3-cyclohexadiene complexes by hydride abstraction with tritylium cations, react similarly to give 5-substituted 1,3-cyclo-hexadienes, and neutral tricarbonyl(n -l,3-cyciohexadiene)iron complexes can be coupled with olefins by hydrogen transfer at > 140°C. These reactions proceed regio- and stereospecifically in the successive cyanide addition and spirocyclization at an optically pure N-allyl-N-phenyl-1,3-cyclohexadiene-l-carboxamide iron complex (A.J. Pearson, 1989). 

Migration of a hydride ligand from Pd to a coordinated alkene (insertion of alkene) to form an alkyl ligand (alkylpalladium complex) (12) is a typical example of the a, /(-insertion of alkenes. In addition, many other un.saturated bonds such as in conjugated dienes, alkynes, CO2, and carbonyl groups, undergo the q, /(-insertion to Pd-X cr-bonds. The insertion of an internal alkyne to the Pd—C bond to form 13 can be understood as the c -carbopa-lladation of the alkyne. The insertion of butadiene into a Ph—Pd bond leads to the rr-allylpalladium complex 14. The insertion is usually highly stereospecific. 

The same regioselective and stereospecific reactions are observed in decalin systems. The 3/3-formate 605 is converted into the a-oriented (j-allylpalladium complex 606, and the hydride transfer generates the fra .s-decalin 607, while the cis junction in 610 is generated from the 3tt-formate 608 by attack of the hydride from the /3-side (609). An active catalyst for the reaction is prepared by mixing Pd(OAc)2 and BU3P in a 1 I ratio with this catalyst the reaction proceeds at room temperature. The reaction proceeded in boiling dioxane when a catalyst prepared from Pd(OAc)2 and BujP in a 1 4 ratio was used[390]. 

The regioselective and stereospecific construction of C-20 stereochemistry is explained by the following mechanism. The Pd(0) species attacks the ( )-/3-carbonate 616 from the a-side by inversion to form the Tr-allylpalladium species 620, which has a stable syn structure[392]. Then concerted decarboxylation-hydride transfer as in 621 takes place from the a-side to give the unnatural configuration in 617. On the other hand, the Tr-allylpalladium complex 622... 

A facile method for the stereospecific labeling of carbon atoms adjacent to an oxygenated position is the reductive opening of oxides. The stereospecificity of this reaction is due to virtually exclusive diaxial opening of steroidal oxides when treated with lithium aluminum hydride or deuteride. The resulting /ra/w-diaxial labeled alcohols are of high stereochemical and isotopic purity, with the latter property depending almost solely on the quality of the metal deuteride used. (For the preparation of m-labeled alcohols, see section V-D.)... 

Some instances of incomplete debromination of 5,6-dibromo compounds may be due to the presence of 5j5,6a-isomer of wrong stereochemistry for anti-coplanar elimination. The higher temperature afforded by replacing acetone with refluxing cyclohexanone has proved advantageous in some cases. There is evidence that both the zinc and lithium aluminum hydride reductions of vicinal dihalides also proceed faster with diaxial isomers (ref. 266, cf. ref. 215, p. 136, ref. 265). The chromous reduction of vicinal dihalides appears to involve free radical intermediates produced by one electron transfer, and is not stereospecific but favors tra 5-elimination in the case of vic-di-bromides. Chromous ion complexed with ethylene diamine is more reactive than the uncomplexed ion in reduction of -substituted halides and epoxides to olefins. ... 

As noted in Chapter 18, the enzymes that require nicotinamide coenzymes are stereospecific and transfer hydride to either the pro-i or the pro-S positions selectively. The table (facing page) lists the preferences of several dehydrogenases. 

NAD (P) " -dependent enzymes are stereospecific. Malate dehydrogenase, for example, transfers a hydride to die pro-/ position of NADH, whereas glyceraldehyde-3-phosphate dehydrogenase transfers a hydride to die pro-5 position of the nicotinamide. Alcohol dehydrogenase removes a hydride from the pro-i position of edianol and transfers it to die pro-i position of NADH. 

The stereospecificity of hydride transfer in dehydrogenases is a consequence of the asymmetric nature of die acUve site. 

Tetrahydro derivatives are formed when either quinoxaline or 6-chloroquinoxaline is reduced with lithium aluminum hydride in ethereal solution. Similar reduction of 2,3-dimethylquinoxaline gives the meso-(cts)-1,2,3,4-tetrahydro derivative. This is shown to be a stereospecific reduction since lithium aluminum hydride does not isomerize the dl-(trans)-compound. Low temperature, platinum catalyzed, hydrogenation of 2,3-dimethylquinoxaline in benzene also gives meso (cis) -l,2,3,4-tetrahydro-2,3-dimethylquinoxaline. ... 

The synthesis of the key intermediate aldehyde 68 is outlined in Schemes 19-21. The two hydroxyls of butyne-l,4-diol (74, Scheme 19), a cheap intermediate in the industrial synthesis of THF, can be protected as 4-methoxybenzyl (PMB) ethers in 94% yield. The triple bond is then m-hydrostannylated with tri-n-butyl-tin hydride and a catalytic amount of Pd(PPh3)2Cl238 to give the vinylstannane 76 in 98 % yield. Note that the stereospecific nature of the m-hydrostannylation absolutely guarantees the correct relative stereochemistry of C-3 and C-4 in the natural product. The other partner for the Stille coupling, vinyl iodide 78, is prepared by... 

Similarly, the hydride reduction of the fluorenone and anthraquinone complexes gives the corresponding secondary alcohols with endo-OH groups resulting from stereospecific attack [134], This strategy is also known in the Cr(CO)3(arene)... 

But in neutral solution, where the complex is present mainly as the hydride, the only product was the a-phenylvinyl complex (CH2=CHPhCo). When the Co(I) complex was formed by reduction with D2 or NaBD4 in CH3OH the reaction in neutral solution gave a product containing a significant amount of deuterium in the position cis to cobalt. This establishes the mechanism as the stereospecific cis addition of Co—D across the double bond, i.e.,... 

Figure 11-4. Mechanism of oxidation and reduction of nicotinamide coenzymes. There is stereospecificity about position 4 of nicotinamide when it is reduced by a substrate AHj. One of the hydrogen atoms is removed from the substrate as a hydrogen nucleus with two electrons (hydride ion, H ) and is transferred to the 4 position, where it may be attached in either the A or the B position according to the specificity determined by the particular dehydrogenase catalyzing the reaction. The remaining hydrogen of the hydrogen pair removed from the substrate remains free as a hydrogen ion.

The stereospecific base-cleavage of the trimethylsilyl group in 1,3-dithiane 1-oxides 499 enables to obtain the specifically deuteriated products 500 (equation 303), A nitro group in y-nitroalkyl sulphoxides 501 (obtained by the Michael addition of nitroalkanes to a, j8-unsaturated sulphoxides) is replaced by hydrogen by means of tributyltin hydride (equation 304). This reagent does not affect the sulphinyl function. The overall procedure provides an efficient method for the conjugate addition of alkyl groups to a, -unsaturated sulphoxides . ... 

Rhodium hydride addition to the enone s-cis conformer through a six-centered transition structure accounts for stereospecific Z(0)-enolate forma-... 

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