Protonation stereoselective

Tliese observed stereoselectivites can be forcned by ryn addition at low temperatut [60a] to afford tlie E adduct Selective for temperatures, requires ritlier forenation allenyl etiolate or isomerization of tlie Z a stereoselective protonation. Recetit mecliat... 

Ono and Kamimura have found a very simple method for the stereo-control of the Michael addition of thiols, selenols, or alcohols. The Michael addition of thiolate anions to nitroalkenes followed by protonation at -78 °C gives anti-(J-nitro sulfides (Eq. 4.8).11 This procedure can be extended to the preparation of a/jti-(3-nitro selenides (Eq. 4.9)12 and a/jti-(3-nitro ethers (Eq. 4.10).13 The addition products of benzyl alcohol are converted into P-amino alcohols with the retention of the configuration, which is a useful method for anri-P-amino alcohols. This is an alternative method of stereoselective nitro-aldol reactions (Section 3.3). The anti selectivity of these reactions is explained on the basis of stereoselective protonation to nitronate anion intermediates. The high stereoselectivity requires heteroatom substituents on the P-position of the nitro group. The computational calculation exhibits that the heteroatom covers one site of the plane of the nitronate anion.14... 

To explain the observed optical induction, a substrate was incorporated into the molecular model of the protein. A substrate such as a-ketoglutarate could be included in the protein model with a geometry that allowed stereoselective protonation of the quinoid intermediate by solvent, consistent with the enantiomeric excess (ee) of the 1-stereoisomer product. Moreover, the geometry consistent with production of the d-enantiomer appeared too sterically crowded for most substrates. However, pyruvic acid, which was the only substrate to favor the d-enantiomer product, was small enough to adopt the alternative geometry and also had the potential to interact with an arginine group. 

The enolate reactivity associated with this approach to C-glycoside synthesis was, however, first developed with octulosonic acid derivatives, such as 283 [114], 284 [115], and 285 [116], and a series of examples involving aldehyde and halide-based electrophiles are shown in Scheme 74. Related studies involving stereoselective protonation of this class of exocyclic enolate have also been described [13] and Scheme 75 illustrates this with an example of reductive samariation (using ethane-1,2-diol, but no HMPA) of an anomeric acetate 286 [117]. 

Propynyl bromides can be enantioselectively converted to chiral allenes by stoichiometric conversion into a propynylchromium(III) complex followed by stereoselective proton transfer from a chiral auxiliary, e.g., (-)-borneol or (-)-menthol120, l2 . Formally, substitution of bromide takes place. 

Starting from a bicyclic cyanomethylamine71 72, mixtures of the alkylated cyanomethylamines were obtained. These were reduced with excellent selectivity to give one diastereomer of the perhydropyrrolo 2,1 -/> oxazole 8 only by stereoselective protonation (see Section D.2.I.). The conversion of 8 to chiral 2-alkylpyrrolidines proceeded quantitatively73. 

Imidazolines (245) have been prepared from (S)-alanine and (S)-proline. Upon hydrolysis (R)-alanine was obtained. This result can be explained in terms of epimeri-zation and stereoselective protonation with asymmetric induction by the chiral center originating from (S)-proline246). 

Asymmetric transamination.2 This planar chiral pyridoxamine analog in the presence of Zn(C104), (l/Zn(C104)2 = 1.0.5) converts a-keto acids into (R)-amino tieids in 60 96%ee. Use of (R)-l in place of (S)-l produces (S)-amino acids with the wime elliciency. Chemical yields range from 50 75%. The preferred solvent is tnel li.mol. The pyridoxal-type analog is recovered in 75-85%yield. The transamination is considered to involve kinetically controlled stereoselective protonation of an octahedral Ztr 1 chelate intermediate. 

Silyl enol ethers of decalones have been synthesized which allow stereoselective protonation of the corresponding enol to be initiated and followed kinetically.291 Pendant groups have been placed so that the relative rates of intermolecular protonation and intramolecular protonation (by the proximate group) can be measured. Examples of groups which give one or other mechanism are detailed CO2- and CO2H typify the latter. 

A further method to induce chirality in the pyridoxamine-mediated transamination reactions was developed by Kuzuhara et al. [13]. They synthesized optically resolved pyridinophanes (21, 22) having a nonbranched ansa chain" between the 2 - and 5 -positions of pyridoxamine. With the five-carbon chain in 21 and 22, the two isomers do not interconvert readily. In the presence of zinc(n) in organic solvents such as methanol, tert-butanol, acetonitrile, and nitromethane, they observed stereoselective transamination between pyridinophanes and keto acids. The highest ee%s are 95 % for d-and L-leucine by reaction of the corresponding a-keto acid with (S)- and (R)- 22, respectively. On the basis of kinetic analysis of the transamination reactions, Kuzuhara et al. originally proposed a mechanism for the asymmetric induction through kinetically controlled stereoselective protonation to the carboanion attached to an octahedral Zn(n) chelate intermediate. However, they subsequently raised some questions about this proposal [14]. 

Electrophilic addition to double bonds gives three-membered ring intermediates with Br2, with Hg2+, and with peroxy-acids (in which case the three-membered rings are stable and are called epoxides). All three classes of three-membered rings react with nucleophiles to give 1,2-difunctionalized products with control over (1) regioselectivity and (2) stereoselectivity. Protonation of a double bond gives a cation, which also traps nucleophiles, and this reaction can be used to make alkyl halides. Some of the sorts of compounds you can make by the methods of this chapter are shown below. 

SCHEME 76. Regio- and stereoselective protonation of the lithium anion generated by 1,6-catalyzed addition of methyllithium onto (2R,6R)-6-methyl-(4, 4 dimethylpent-2 -yn)-yliden-2-(l,l-dimethyl-ethyl)-l,3-dioxan-4-one366... 

The pyridoxal phosphate-dependent ornithine decarboxylase converts S-ornithine to 1,4-diaminobutane (equation 23). It was reported that (R)-hex-5-yne- 1,4-diamine is an irreversible inhibitor of the enzyme and evidence was presented in favor of the proposition that the enzyme performs stereoselective proton abstraction of the pro (R)... 

The lithium salt 276 has been prepared by Boche and coworkers with MeLi in ether, n-BuLi in THF and LDA in THF it reacts with D2O to give the corresponding 1-D-compound. Thus, 276 is also comparatively stable . The cis,cis-sulfone 277 reacts with n-BuLi in THF, followed by protonation after 5 min, to give the trans,trans-su fonc 278 (undoubtedly via the corresponding Li compounds at which stage the isomerization takes place although stereoselective protonation of a pyramidal or planar carbanion is not excluded) ... 

Electrophilic additions to bicyclo[1.1.0]butanes are highly stereoselective. Protonation occurs predominantly with retention of configuration and leads to proton incorporation cis to the methyl moiety. Thus, acetolysis of l,2,2-trimethylbicyclo[1.1.0]butane (5) in acetic acid-d leads to the monodeuterated cyclopropylmethyl compounds 6 and 7 with retention of configuration. ... 

Various aluminum hydrides have been found to induce the reductive ring opening of [2.2.1] and [3.2.1] oxabicydic compounds. Metz found that the treatment of sultone 258 with Red-Al resulted in the overall net SN2 addition of hydride and ring opening [165]. When 260 was found to also give 261 under the same reaction conditions, the mechanism postulated to account for this transformation was an initial deprotonation of the sultone 258 by Red-Al and ring opening, followed by the 1,6-delivery of hydride via aluminate 259, and stereoselective protonation, Eq. 162. 

By examining Scheme 1 it is possible to verify the key role of the base as catalyst for the overall process and to justify the lack of stereoselectivity which, in general, has been observed in nitroaldol additions. In fact, the reversibility of the nitroaldol process, as well as the difficulty of a stereoselective protonation of the stereogenic center of the nitronate intermediates, leads to a mixture of diastereomeric 2-nitro alcohols. 

Although detailed investigations are only known for enolate ions1 2, the effects observed in those cases should also be taken into account for nitroates and carbanions since they may influence the outcome of stereoselective protonations. Principally, all of these anionic species occur as ion pairs and their aggregates, which equilibrate slowly under the usual conditions (low temperature, diethyl ether or THF as solvent). Therefore, the very rapid protonation reaction may result in different stereoselections from each of the aggregates. 

In the case of ehiral carbanions (mostly organolithium compounds), this stereogenic center itself promotes stereoselective protonation. 

Reports on organolithium compounds with internal heteroatom stabilization and their reactions with alkylating agents7 12 -14 are informative for stereoselective protonations and deuter-ations. 

Stereoselective protonation of enamines of the following type yield immonium salts under kinetic control which are subsequently transformed by cleavage of the / -diketones into the keto acids 3133. 

The lithium enolate of rac-methyl 4-butylthio-2-methyl-3-pentenoate is stereoselectively protonated by (1,2 5,6)-di-0-isopropylidcne-a-n-glucofuranose155. 

Since samarium diiodide is only a one electron donor, two equivalents of the metal are required in order for the reaction to proceed. The first electron donated from the samarium produces a chiral ketyl radical 30 which undergoes enantioselective addition to the acrylate according to the chelated transition state shown in 32. The second electron donation then provides a chiral samarium enolate intermediate 33 that can potentially undergo stereoselective proton transfer in the formation of a second chiral center. 

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