Nucleophile-induced racemization

NMR time scale for all counterions studied, i.e., Br, I-, C104, CF3S03, including also Cl- at low temperature. The rate constant was estimated to be at least of the order of 103 second-1 at 30°C. In light of this result it is reasonable to postulate a ligand exchange process for the nucleophile-induced racemization of optically active silanes (discussed in Section V,F). 

Activation Parameters of Nucleophile-Induced Racemization of Triorganosilanes... 

The expansion of coordination at silicon. Pentacoordinated species seem to be quite intimately involved in many processes taking place at silicon. Expansion of coordination is the fundamental step not only in the nucleophilic induced racemization reviewed some years ago (13), but also in nucleophilic substitution activated by nucleophiles. A part of this review is devoted to the stereochemical and mechanistic aspects of nucleophilic activation. Furthermore, in connection with a possible isomerization of trigonal bipyramidal silicon by Berry pseudorotation, the dynamic stereochemistry of pentacoordinated silicon compounds is discussed. 

In the past few years, numerous experimental results have illustrated the fundamental importance of penta- and hexacoordinate silicon species in reactions at silicon. The implication of pentacoordinate intermediates in substitution reactions at silicon is now well accepted (10, 11) the nucleophilically induced racemization (13,268) and hydrolysis (or alcoholysis) of halosilanes (268, 269), both controlled by entropy factors, take place through expansion of coordination at silicon. Pentacoordinate species with two or three carbon atoms attached to silicon have been isolated (129, 155) and finally, five-coordinate anions with five carbon atoms around silicon have been identified in the gas phase (107). This shows how much the expansion of coordination at silicon is an energetically favorable process. 

A related process is implicated in the nucleophilically induced racemization at tetracoordinate halogenosilanes (13), which has been shown to involve two molecules of nucleophilic agent. Racemization arises from an equilibrium between five- and six-coordinate intermediates (eq. [116]). This process is controlled by entropy. It is characterized by a highly negative activation entropy and a low or sometimes negative activation enthalpy. 

This process relies on rapid base-induced racemization of the azlactone and rate-limiting ring opening by the alcohol nucleophile. In this process the DMAP derivative 79a acts as both Bronsted-basic and as nucleophilic catalyst. With 2-propanol as reagent enantiomeric excesses up to 78% were achieved for the product amino acid esters [87]. 

Acid-induced racemization and isomerization of chiral allylic alcohols. Bimolecular nucleophilic displacements in allylic compounds are known to proceed via the four possible pathways shown in Scheme 19. 

Initial attempts to extend this procedure to the synthesis of peptides gave the products in good yields, at least at the level of model dipeptides when DMAP was added in catalytic amounts.This may be attributed to the intermediate formation of the highly reactive 1-(tert-butoxycarbonyl)-4-(dimethylamino)pyridinium tert-butyl carbonate (10, Scheme 7) which facilitates the nucleophilic addition of the amino acid carboxylate anion at the tert-butoxycarbonyl group of the pyridinium system. Such an intermediate has been confirmed by Knolker and Braxmeier.t The addition of DMAP was not found to induce racemization. Whether this procedure is applicable in repetitive steps of peptide synthesis, is still questionable since tert-butoxycarbonylation of the amino component, at least to some extents, cannot be excluded. 

In this context, the existence of stable penta- and hexacoordinate silicon derivatives and their structure have elicited considerable interest. Isomerization processes of these compounds are also of importance, since penta- or hexacoor-dinate intermediates are implicated in the substitution and racemization of tetracoordinate silicon derivatives. For all these reasons, we include here (i) some available structural data for hypervalent silicon compounds (the review is not intended to be exhaustive), (ii) recent reports concerning the nucleophilically induced substitution and racemization reactions at silicon, and (ii) a criti-... 

Corriu also criticizes this mechanism as it cannot account for the nucleophile- induced epimerization of chlorocyclobutanes114. As discussed earlier, in strained systems retentive substitution predominates, such that two consecutive such substitutions by HMPA would only lead to retention. However, whilst retention is the major pathway, inversion may still occur as a minor route. Whereas retention would not reveal itself, one invertive substitution in the equilibrium 39 would lead to racemization. Such a pathway is... 

It has been shown that a complete shift in stereochemistry of the nucleophilic reactions of (29), with alkyl halides such as 2-bromobutane or cis-2-bromomethoxycyclohexane, from racemization to complete inversion, is induced by increase in the inner-sphere stabilization of the transition state from 0 to 3 kcal mol" This has been ascribed to competition between inner-sphere 5)vr2 and outer-sphere electron-transfer processes the former being extremely sensitive towards inner-sphere stabilization. 

If the interconversion of the Jt-allyl intermediates 34 and 35 is much slower than nucleophihc attack, the product distribution depends on the nature of the substrate. In this case the two enantiomeric chiral substrates 30 and ent-30 are converted to the corresponding product enantiomers 36 and ent-36 with overall retention of configuration. Starting from a racemic mixture of 36 and ent-36, the two product enantiomers 36 and ent-36 are formed in a 1 1 ratio and, therefore, a chiral catalyst cannot induce enantioselectivity (except for kinetic resolution). However, the analogous reaction of the hnear, achiral substrate 31 can be rendered enantioselective if a chiral catalyst is used that adds preferentially to one of the enantiotopic faces of 31 to give either complex 34 or 35. In this case, the enantioselectivity is determined in the oxidative addition of the substrate to the catalyst while nucleophilic addition to the 7i-allyl intermediate is irrelevant for the enantiomeric excess of the overall reaction. The relative rates of k-O-k isomerization and the other processes shown in Scheme 15 strongly depend on... 

A second-order rate equation has been obtained for the racemization of various chloro- and bromosilanes induced by nucleophiles (HMPT, DMSO, DMF) (13,268-269),... 

ROP is carried out in solution, in the melt, in the bulk or in suspension. The involved mechanism can be ionic (anionic or cationic), coordination-insertion or free-radical polymerization [19].The cationic pol)rmerization is initiated by only two catalysts, trifluoromethane-sulphonic acid and its methyl ester [10, 15]. Initiators such as potassium methoxide, potassium benzoate, zinc stearate, n-, sec-, fer-butyl lithium or 18-crown-6-ether complexes are added for the anionic polymerization to induce a nucleophilic reaction on the carbonyl to lead to an acyl-oxygen link cleavage. According to Jedkinski et al. only the primary alkoxides, such as the first mentioned catalyst, can yield polymers with negligible racemization, transesterification and termination [10]. 

A more recent application of a similar cyclization is during a synthesis of (+)-preussin 230 in which a key step is mercury(II)-induced cyclization of the ynone 228 to give the keto-dihydropyrrole 229 <94JOC4721>. There are a number of notable features of this reaction. Firstly, despite conjugation to the keto group, the alkyne remains sufficiently nucleophilic to interact with the electrophilic mercury, the intermediate ketone is stable to racemization and the Af-Boc group does not interfere, presumably because the 5-endo-dig mode is favoured. 

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