Stereospecific protonation

In the Au(I) catalysis of electron-poor alkynes such as 4, the catalytically active species is likely to be a cationic ligand-stabilized gold(I) Jt-complex, as in previously reported additions of oxygen nucleophiles to alkynes [5], Gold catalysts are very soft and thus carbophilic rather than oxophilic. On the basis of this assumption a plausible mechanism can be formulated as shown in Scheme 6. The cationic or strongly polarized neutral Au(I)-catalyst coordinates to the alkyne, and nucleophilic attack of the electron-rich arene from the opposite side leads to the formation of a vinyl-gold intermediate 7 which is stereospecifically protonated with final formation of the Z-olefm 8 [2, 4]. Regioselectivity is dominated by elec-... 

L-aspartate. They observed that tritium was introduced at C-4 of the cofactor from the Re face to the extent of over 90%. Thus the exposed face of the coenzyme-substrate complex in the modified enzyme is the Re face as in the holoenzyme rather than the Si face as in the complex of the normal enzyme with L-aspartate. Yet this modified enzyme is still able to undergo the half-transamination reaction with conversion of active site bound PLP to PMP [45] and does so with stereospecific protonation of the cofactor from the Si face [46]. According to this result, a change in the exposed face of the cofactor upon transaldimination or a conformation in which the Si face of C-4 is exposed in the coenzyme-substrate complex are not requirements for catalytic activity. Likewise, the face on which reactions take place in the catalytic process is not necessarily the face that is most accessible to external reagents. 

Barnard and Akhtar [84] speculate that the same group (X) of the enzyme is involved in the deprotonation of the carboxyl group and in the stereospecific protonation of the vinylogous enamine (75) (Fig. 41). 

As is evident, the reaction proceeds with very high stereoselectivity, since the enzyme can perform stereospecific / -protonation (protonation from only one side) of the enamine leading to dihydroxyacetone phosphate. 

The results suggested that a group from fhe profein abstracfs a proton from fhe a posihon and transfers if on fhe same side of fhe n system (suprafacial transfer), adding it to the si face of fhe C=N group as shown in Fig. 14-8. Later, fhe same stereospecific proton transfer was demon-sfrafed for the PLP present in the holoen-zyme. Not surprisingly, the D-amino acid aminotransferase adds the proton to the re face of the C = N group. 

Two new syntheses of racemic mesembrine have been described. In the first, outlined in Scheme 1, an improved synthesis of the penultimate 2-pyrroline (8) was achieved annelation of this afforded ( )-mesembrine (9). The second (Scheme 2) incorporates a regioselective borohydride imide reduction. Investigations on the biosynthesis of mesembrine alkaloids have revealed that a stereospecific protonation occurs at C-7 [see formula (9)] as one of the late stages. ... 

One question that still remains concerns the donor responsible for protonating the enolate intermediate. In the structure of the C16 substrate bound to InhA in the presence of NAD, the thioester carbonyl is in the s-cis conformation so that the si face of the C3 carbon is oriented toward the cofactor. In this conformation, the face of the C2 carbon is also oriented toward the cofactor, making it difficult to see how the enzyme could stereospecifically protonate the substrate without a significant structural reorganization. However, the 2 -hydroxyl of the cofactor ribose is on the correct face of the substrate and could in principle be the source of the proton. ... 

Deprotonation of cationic olefin complexes [Fe(CO)2(olefin)( -C6H5)]+ gives j -allyl complexes with a stereochemistry which is accounted for by preferred abstraction of an allylic proton trans to the Fe—olefin bond. The reverse reaction, protonation of the allyl complexes, is, however, non-stereospecific. Proton abstraction from the allyl alcohol derivative (3) by EtsN gives the lactone (4) in only one diastereoisomeric form, probably as a result of the alcohol in (3) having a preference for the conformation illustrated. Addition of MeO to similar olefinic cations (5) proceeds with high regioselectivity while amines add similarly to give complexes of... 

The stereospecific proton removal from 1.20) to give (L21) can be understood simply as follows Imagine that at the active site of the enzyme there is one binding site specific for the ethanol OH and one specific for CH3. This uniquely locates the molecules on the enzyme surface as shown in 1.20). Now imagine that the enzyme/co-enzyme proton removal can only occur physically from above the plane of the paper. This results in unique removal of the pro-R proton. There is no way on this model that the pro-S proton can be removed. A similar argument can be applied to proton addition to 1.21) and to... 

The relationship of cyclic monoterpenes, e.g. 4.3) and 4.53), to geranyl pyrophosphate 4.41) is an obvious one. The tram double bond in 4.41) means that 4.41) cannot cyclize directly to give monoterpenes such as 4.53), and neryl pyrophosphate 4.51) may be more directly involved in biosynthesis. [A cell-free preparation of Mentha piperita has been obtained which will catalyse the conversion of neryl pyrophosphate 4.51) into a-terpineol 4.3) [65].] The conversion of geraniol 4.2) into nerol 4.49) is well known and involves a stereospecific proton removal from C-1 loss of a proton indicates that the aldehyde 4.50) is involved in double-bond isomerization [66]. Initiation of cyclic monoterpene formation can be seen as... 

Finally, the use of isotopes in carbon-acid substrates is an invaluable tool for the determination of the stereochemistry of the enzymatic proton transfer. In contrast to organic reactions, stereospecific proton transfers are the rule, rather than the exception, in enzymatic reactions, owing to the inherently asymmetric nature of the protein surface. An example is the pair of isotopic exchange reactions between dihydroxyacetone phosphate and tritiated water catalysed by the enzymes aldolase and triose phosphate isomerase [17]. In the two cases a different a-hydrogen of the ketone is exchanged with water, leading to the two discrete monotritiated derivatives 1 (labelled by the isomerase) and 2 (labelled by the aldolase) ... 

Trofimov, B.A., A.V. Ivanov, LA. Ushakov et al. 2011. Stereospecific protonation of pyrrole-2-carboxaldehyde Z-oximes as a result of through-space cation stabilization with oxime hydroxyl. Mendeleev Commun 21 103-105. 

Suginome, H., Ohki, T, Nagaoka, A., and Senboku, H., Photoinduced molecular transformations. 133. New photoinduced deconjugation of steroidal a,P-unsaturated cyclic ketone oxime into the P,y-isomer involving stereospecific proton transfer,/. Chem. Soc., Perkin Trans. 1, 1849, 1992. 

Effect of HMPA on Protonation. The protonation of (9-anthryl)arylmethyllithium with various oxygen and carbon acids in THF or in THF-HMPA had a significant effect on the product ratio of C-a vs. C-10 protonation (eq 27). Another study found that a nitronate protonation led to mainly one diastereomeric product in a THF solution containing HMPA or DMPU (eq 28). Panek and Rodgers observed stereospecific protonation of 10-t-butyl-9-methyl-9-lithio-9,10-dihydroanthracene >99% cis protonation was observed in THF or ether with greater than >99% trans protonation observed in HMPA. 

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