Stereochemical inversion

Stereochemical inversion of the tetrahedral arrangement of bonds to the carbon at which substitution occurs... 

Pyramidal inversion (Section 24.2) The rapid stereochemical inversion of a trivalent nitrogen compound. 

CU4S4] species in which the TADDOL-derived ligand was an unexpected sul-fur-monodentate and not a S/X-bidentate ligand. This hypothesis was confirmed by NOE NMR spectroscopy that suggested a different structure for the Cu complex of the alcohol ligand relative to the methylether and the dimethylamino ligands, which could explain the observed stereochemical inversion. 

As a free base, the Ar-Cfb-N protons would present themselves as a simple singlet. The lone pair of electrons on the nitrogen invert very rapidly on the NMR timescale and so the environment of the two protons is averaged and is therefore identical. However, on forming a salt, the whole process of stereochemical inversion at the nitrogen is slowed down dramatically because the sequence of events... 

A new analytical method [34] for the enantiomeric purity of epoxide pheromones as well as a new method [35] for stereochemical inversion of saturated epoxides were reported by Oliver. 

Several aluminum biphenolate complexes have been investigated as initiators for the ROP of PO.810,935 Unlike the TPP and salen-based systems, a cis coordination site is realistically accessible and in theory an alternative cis-migratory mechanism to the backside attack pathway might operate. However, NMR analyses on the resultant PPO show that stereochemical inversion still occurs when the biphenolate initiators are used (Scheme 22). It has also been confirmed that the same process occurs with the Union Carbide calcium alkoxide-amide initiator for both PO and CHO.810... 

One of the questions that is commonly addressed in mechanistic proposals is how is the active site water activated for nucleophilic attack on the phosphodi-ester bond Numerous combinations of amino acid side chains and zinc ions have been proposed for this role, but there has been little consensus. Critical to all the general base hypotheses is a quite reasonable assumption about catalysis by PLC5c The nucleophilic attack on the phosphodiester moiety proceeds via an in-line mechanism resulting in stereochemical inversion of configuration at phosphorus [86]. While this assumption is consistent with the position of the active site water molecules in the PLCBc-phosphonate inhibitor complex [45], it has not yet been established experimentally. This structure provides a detailed picture of how the amino acid side chains of Glul46, Glu4, Asp55, and the zinc ions interact with the phosphonate inhibitor (Fig. 12), so mechanistic hypotheses now have a structural basis. 

A S 2 reaction proceeds with complete stereochemical inversion while... 

Stereochemical inversion of a 6-lactone.1 The 0-lactone 2, obtained by standard lactonization of 1, was inverted to 4 by hydrolysis to the hydroxy acid 3 followed by laclonizalion with triphenylphosphine and diethyl azodicarboxylate. This method evidently involves activation of the hydroxyl group followed by an intramolecular Sn2 attack by the carboxyl group. Two other reagents can he used for this purpose ... 

Most Williamson Ether Syntheses proceed by an Sn2 mechanism. Stereochemical inversions can be expected, where appropriate, as a result. 

Scheme 29 The stereochemical inversion of (S)-(+)- to (R)-(-) reticuline via the enzymes (S)-reticulinium oxygenase and 1,2-dehydroreticuline reductase. The 1,2-dehydro-reticulinium ion is proposed as an intermediate.

Attack by nucleophiles on the electrophilic ir-allylpalladium complex can take place by two distinct mechanisms, which have opposite stereochemical consequences. Stereochemical inversion is achieved by attack of the nucleophile directly on the allyl ligand on the face opposite the palladium (equation 148). Retention is achieved by attack of the nucleophile at the metal center, followed by reductive elimination (equation 149). The reductive elimination step could proceed through an V-allylpalladium-Nuc species or directly from an i)3-allylpalladium-Nuc complex. Recent evidence strongly suggests the latter pathway.384... 

In a recent series of studies focused on the synthetic utility of alkenyliodo-nium salts, ( )-/J-phenylethenyl(phenyl)- and ( )-l-hexenyl(phenyl)iodonium tetrafluoroborates, 22 and 23, were utilized for alkenylations of a range of soft, anionic nucleophiles (Scheme 45) [128-135]. In all cases but one, alkenylations with 22 occurred with retention of configuration, while alkenylations with 23 occurred with inversion of configuration. Only the dialkyl phosphoroselenolate salts gave mixtures of (Z)- and (fj)-products with 22 [132]. Furthermore, although cuprous iodide was used to catalyze the reactions of 22 and 23 with the phosphorothioate and -dithioate salts, the stereochemical results were the same [131,133]. It was generally assumed that retention was an outcome of the ligandcoupling or addition-elimination pathways, while stereochemical inversion was attributed to the vinylic... 

Available evidence (14,15) favors the pathway for pyruvate kinase by way of phosphorylation of pyruvate enol. Furthermore, J. Knowles and his coworkers (16,17), using chiral thiophosphates and chiral (160,170,180) phosphate have shown that pyruvate kinase transfers phosphate from phosphoenolpyruvate to ADP with stereochemical inversion at phosphorus. Since monomeric metaphosphate is presumably planar, a chemical reaction by way of that ion should proceed with racemization. In the active site of an enzyme, however, all components might be held so rigidly that racemization need not occur. Furthermore, no information is yet available on the detailed mechanism of reactions catalyzed by cytidine synthetase our own experiments, designed to distinguish among the mechanisms here discussed, are as yet incomplete. 

The potential contamination from either stereochemical impurities or stereochemical inversion of NSAID S (such as etodolac) that might take place when using ethyl chloroformate as the derivatizing agent in the sample preparation described above [33] was investigated in a separate study [34]. The study concluded that the extent of stereochemical conversion induced by assay procedures was small (approximately 1%) for... 

Figure 2.5. Reaction sequence for the biosynthesis of fatty acids de novo by the animal FAS. The condensation reaction proceeds with stereochemical inversion of the malonyl C-2, the (3-ketoacyl moiety is reduced by NADPH to D-(3 hydroxyacyl moiety, which then is dehydrated to a trans-enoyl moiety finally, the enoyl moiety is reduced to a saturated acyl moiety by NADPH, with the simultaneous addition of a solvent proton. The two C atoms at the methyl end of the fatty acid are derived from acetyl-CoA, the remainder from malonyl-CoA. The entire series of reactions takes approximately 1 second. PSH, phosphopantetheine. (Reprinted from Prog, in Lipid Res., vol. 42, S. Smith, A. Witkowski and A.K. Joshi, Stuctural and functional organization of the animal fatty acid synthase, pp. 289-317, copyright (2003), with permission from Elsevier).

Holland s group40 has shown that the most versatile biotransformation using whole cell biocatalyst is the one using the fungus species NRRL 4671. From analysis of the sulfoxidation of a large number of substrates (> 90), they recently proposed a predictive model for chiral sulfoxidation by the fungus. The model (Fig. 2), developed from energy-minimized (MM+) structures of substrates produced by Hyperchem, is able to explain the stereochemical inversion seen for sulfoxidation of some phenyl alkyl sulfides, such as phenyl vinyl and phenyl hexyl sulfide. 

Fig. 24. Stereochemical inversion in the ribonuclease-catalyzed hydrolysis of emit/-2, 3 -cyclic UMPS in H O.

Fig. 25. Stereochemical inversion in the 3 3 -cyclic AMP phosphodiesterase-catalyzed hydrolysis of (Sp)-3, 5 -cyclic AMPS in H O.

The positive ORD curve of this reference compound established the (S) configuration of the enzymically derived sample and also demonstrated that stereochemical inversion at the C-2 of glycerol takes place during the dioldehydratase reaction, exactly as was observed during the rearrangement of 1,2-propanediol to pro-pionaldehyde. 

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