Stereochemistry Reaction Cycles

The optical rotations of the products show that all of these reactions are stereoselective. By the following reaction cycle, it can be proved that reaction 30a - 32a proceeds with retention of configuration of the metal center. Starting with the (—)365-methyl compound 31a, the (-l-ias-bromo complex 32a can be arrived at in two ways in a one-step or a two-step reaction. Consequently, the Fe—C bond in 31a can be directly cleaved by Br2, or it can first be cleaved by I2, and then, in a second step, the corresponding (-)365-iodo derivative 30a can be converted into the (-)365-bromo compound 32a. If the same stereochemistry for the cleavage of the Fe—C bond in 31a by the halogens Br2 and I2 is assumed, the transformation step (-)385-iodo compound 30a - (-)365-bromo compound 32a must necessarily occur with retention of configuration (58). 

Cram, D. J., Cram, J. M. Stereochemical Reaction Cycles. 31, Stereochemistry... 

However, in contrast to MMO, AMO is not inhibited by ethyne, and its reactivity is only mildly affected by the presence of propyne [16]. Since both enzymes also display different stereochemistries despite having homologous active sites, it has been speculated that MMO and AMO employ alternative catalytic mechanisms [16]. While the observation of AMO activation by hydrogen peroxide [160] suggests the formation of a possible diiron-peroxo intermediate in the reaction cycle, the enzyme s inability to oxidize methane indicates that no Q-like diferryl-oxo species may be formed [98]. Hence, small differences in the coordination environment of the diiron centers in AMO and MMO lead to significant variations in substrate specificity and reactivity. 

Elucidating the stereochemistry of reaction at prochirality centers is a powerful method for studying detailed mechanisms in biochemical reactions. As just one example, the conversion of citrate to (ds)-aconitate in the citric acid cycle has been shown to occur with loss of a pro-R hydrogen, implying that the reaction takes place by an anti elimination mechanism. That is, the OH and H groups leave from opposite sides of the molecule. 

Problem 9.26 The aconitase-catalyzed addition of water to ds-aconitate in the citric acid cycle occurs with the following stereochemistry. Does the addition of the OH group occur on the Re or the Si face of the substrate What about the addition of the H Does the reaction have syn or anti stereochemistry ... 

In recent years, a great variety of primary chiral amines have been obtained in enantiomerically pure form through this methodology. A representative example is the KR of some 2-phenylcycloalkanamines that has been performed by means of aminolysis reactions catalyzed by lipases (Scheme 7.17) [34]. Kazlauskas rule has been followed in all cases. The size of the cycle and the stereochemistry of the chiral centers of the amines had a strong influence on both the enantiomeric ratio and the reaction rate of these aminolysis processes. CALB showed excellent enantioselec-tivities toward frans-2-phenylcyclohexanamine in a variety of reaction conditions ( >150), but the reaction was markedly slower and occurred with very poor enantioselectivity with the cis-isomer, whereas Candida antarctica lipase A (GALA) was the best catalyst for the acylation of cis-2-phenylcyclohexanamine ( = 34) and frans-2-phenylcyclopropanamine ( =7). Resolution of both cis- and frans-2-phenyl-cyclopentanamine was efficiently catalyzed by CALB obtaining all stereoisomers with high enantiomeric excess. 

Michalski, M., Mikolajczyk, M., and Omelanczuk, ]., Stereochemistry of nucleophilic displacement reaction at thiophosphoryl centre. An example of the Walden cycle involving phosphorus, Tetrahedron Lett., 1779, 1965. 

To probe the reaction mechanism of the silane-mediated reaction, EtjSiD was substituted for PMHS in the cyclization of 1,6-enyne 34a.5 The mono-deuterated reductive cyclization product 34b was obtained as a single diastereomer. This result is consistent with entry of palladium into the catalytic cycle as the hydride derived from its reaction with acetic acid. Alkyne hydrometallation provides intermediate A-7, which upon cw-carbopalladation gives rise to cyclic intermediate B-6. Delivery of deuterium to the palladium center provides C-2, which upon reductive elimination provides the mono-deuterated product 34b, along with palladium(O) to close the catalytic cycle. The relative stereochemistry of 34b was not determined but was inferred on the basis of the aforementioned mechanism (Scheme 24). 

Whereas, from all of these informative 1H-PHIP-NMR spectra, the structure of the dihydride intermediate (including geometric details about peculiar bonding therein) can be determined rather exactly and reliably, a degree of uncertainty remains as to whether this intermediate represents the major or the minor diastereomer according to the nomenclature of Halpern [27]. This is the consequence of different kinetic constants associated with the two alternative cycles with different stereochemistry, and which accounts for the major and minor reaction product (Fig. 12.18). In fact, it is the difference in the rate... 

A crystalline sample of this supramolecular assembly was irradiated with UV light and the formation of the corresponding cyclobutane 91 with syn-anti-syn stereochemistry was observed. In contrast, the photodimerisation of trans-stilbenoid-bis(dialkylammonium) salts does not take place in the absence of the macro cycle, indicating the importance of pre-organizing the stilbenoid units (which requires the presence of the anion) for this solid-state reaction to occur. 

In the first step of the catalytic cycle a coordinatively unsaturated Pd(0) species - which is formed in situ from Pd(OAc)2 and PPh3 -inserts into the alkenyl-I bond of 8 to give 42 (syn addition). Next an insertion of the terminal olefin into the cr-alkenyl-C-Pd bond forms the six-membered ring in 43. The stereochemistry can be explained by 41 reaction of the si-face of the exomethylene group involves a nearly coplanar orientation of the Pd-C bond and the C-C-zrbond. The siloxy substituent is placed pseudo-equatorially. 

General aspects of the stereochemistry and mechanism of PLP-catalyzed reactions have been reviewed by Floss and Vederas75 and Miles.77 In this section we briefly describe the catalytic cycle of tryptophanase. New transient intermediates have recently been detected in this cycle by Phillips et a/.,41-42-78 using rapid-scanning stopped-flow spectrophotometry, and they are included in the reaction mechanism depicted in Fig. 9.13. 

At ambient temperatures and in neat CH3I as a solvent, IR bands and NMR signals for complexes 4.2-4.4 are seen. The stereochemistry of 4.2 as shown in the catalytic cycle is consistent with the spectroscopic data. The relative thermodynamic and kinetic stabilities of complexes 4.1-4.3 under these conditions have also been estimated. The data show that 4.2 is unstable with respect to conversion to both 4.3 and 4.1. In other words, 4.2 undergoes facile insertion and reductive elimination reactions. 

The overall enantioselectivity of the catalytic process obviously depends on the relative speed with which the left and right catalytic cycles of Fig. 9.3 operate. Oxidative addition of dihydrogen is found to be the rate-determining step. Therefore, the relative rates of conversion of 9.19 to 9.21 on the one hand and 9.20 to 9.22 on the other determine which enantiomer of the organic product would be formed preferentially. The reaction between 9.28 and a-acetamido methyl cinamate has been monitored by multinuclear NMR, and both 9.19 and 9.20 have been identified. Depending on the stereochemistry of the chiral phosphine, one of these two diastereomers is preferentially formed. 

Apart form the aforementioned highly enantioselective hetero-Diels-Alder reactions, that proceed with very low catalyst loadings, the catalytically accessible enolates have also been used for related intramolecular Michael reactions (Philips et al. 2007) and for the desym-metrization of 1,3-diketones yielding cyclopentenes via an intramolecular aldol reaction (Wadamoto et al. 2007). The formation of cyclopentenes, however, presents a special case, so—depending on the stereochemical nature of the enone substrates (s-cis or s-trans) and the stereochemistry of the final products—two different mechanisms are discussed in the literature. Whereas /ran.v-cycl open (cries are proposed to be available upon conjugate addition of a homoenolate to chalcones,... 

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