Stereoselection cation

Scheme 6.32. Stereoselective cationic (ebthi)Zr-catalyzed [4 + 2] cycloaddition involving an unsaturated aldehyde.

Johnson in 1993 described an approach to racemic p-amyrin involving application of a biomimctic polyene cyclization.7 In the same year Corey accomplished the enantioseleetive synthesis of compound 4. a key intermediate that opened the way to stereoselective preparation of compounds I, 2. and 3 8 A key step in the synthesis of P-amyrin (1) was the introduction of chiral oxazaboroli-dines for enantioseleetive carbonyl reduction. Ba ed on these methods, generation of an enantiomerically pure epoxide and its stereoselective cationic cyclization led to the pentacyclic system of structure 1 Diastereoselective cyclopropanation and an intramolecular protonation of a carbanion represent other interesting steps in this total synthesis. 

The interesting structure of zeolites allows the incorporation and immobilization of suitable cations or chiral catalysts on the surface of zeolitic pores. These processes not only enhance the available surface area but also provide highly structured and confined cavities that can increase stereoselectivity. Cation-exchanged zeolites, such as KY and CsY, have received much attention as solid base catalysts owing to the following advantages (i) easy separation from the reaction mixture, (ii) reusabihty, (iii) easy modification of their surface and pore size, and (iv) use of nonpolluting natural minerals [4]. 

Corey s group has also demonstrated the power of epoxide-initiated, stereoselective cationic cyclizations,... 

Serratenediol, a pentacyclic triteipenoid containing a unique seven-membered central ring has been concisely synthesized using double epoxide-initiated stereoselective cationic polycyclizations mediated by MeAlClj as key steps (Scheme 9.44) [17h]. (+)-a-Onocerin has been also synthesized in four steps via double epoxide-initiated stereoselective polycychzations (Schane 9.44) [17i]. 

Stereoselective cis-dihydroxylation of the more hindered side of cycloalkenes is achieved with silver(I) or copper(II) acetates and iodine in wet acetic acid (Woodward gly-colization J.B. Siddall, 1966 L. Mangoni, 1973 R. Criegee, 1979) or with thallium(III) acetate via organothallium intermediates (E. Glotter, 1976). In these reactions the intermediate dioxolenium cation is supposed to be opened hydrolytically, not by Sn2 reaction. 

Cyclopentene derivatives with carboxylic acid side-chains can be stereoselectively hydroxy-lated by the iodolactonization procedure (E.J. Corey, 1969, 1970). To the trisubstituted cyclopentene described on p. 210 a large iodine cation is added stereoselectively to the less hindered -side of the 9,10 double bond. Lactone formation occurs on the intermediate iod-onium ion specifically at C-9ot. Later the iodine is reductively removed with tri-n-butyltin hydride. The cyclopentane ring now bears all oxygen and carbon substituents in the right stereochemistry, and the carbon chains can be built starting from the C-8 and C-12 substit""" ... 

Honk et al. concluded that this FMO model imply increased asynchronicity in the bond-making processes, and if first-order effects (electrostatic interactions) were also considered, a two-step mechanisms, with cationic intermediates become possible in some cases. It was stated that the model proposed here shows that the phenomena generally observed on catalysis can be explained by the concerted mechanism, and allows predictions of the effect of Lewis acid on the rates, regioselectivity, and stereoselectivity of all concerted cycloadditions, including those of ketenes, 1,3-dipoles, and Diels-Alder reactions with inverse electron-demand [2],... 

Hetero-substituted 2-alkenyllithium compounds, however, show useful levels of regio- and stereoselectivity in reactions with aldehydes, in particular if the cation is held at one terminus of the allylie system by electron-withdrawing or chelating groups. 

The addition of a vast number of mainly hetero-substituted allyllithium derivatives to carbonyl compounds has been studied, yet only a few examples proceeding with a preparatively useful level of stereoselectivity have been reported. As many methods were developed before the crucial role of the cation was realized, improvements are possible by simple metal exchange. Some reviews, which collect these reagents, arc cited in Section D.l.3.3.3.1.1. 

The presence of a large excess of lithium salt decreases the stereoselectivity when the reaction is performed under kinetic control. These results and those reported for deuteration (see Section D. 1.1.1.5.) show that this effect is only observed when electrophilic assistance of the lithium cation is involved. 

These results may be explained by a chelation-controlled mechanism A with M representing a complex of JVtg(ll), Ce( 111) or of both cations. The highly stereoselective addition of the organocop-per reagent can be rationalized either by the dipolar model B or the Felkin-Anh model C (see also ref 12). 

The amidoalkylation of certain allylsilanes with a glycine cation equivalent shows low stereoselectivity 84. 

Moderate stereoselectivity is observed in the reaction of a glycine cation equivalent with a silyl enol ether86. 

Only one example, showing high stereoselectivity, is known in this class of reactions. On treatment of the acyclic glycine cation equivalent 1 (see Appendix), containing the ( + )-cam-phor-10-sulfonamide ester as a chiral auxiliary, with boron trifluoridc and anisole at 0"C a mixture of aromatic substitution products is obtained in essentially quantitative yield 55. Besides 11 % of cuV/io-substitution product, the mixture contains (R,S)-2 and its (/ ,/ )-epimer in a ratio >96 4 (NMR). The same stereoisomer 2 predominates when the reaction is conducted in sulfuric acid/acetic acid 1 9, although the selectivity is slightly lower (91 9 besides 25% of ortho substitution). 

Epoxidations of chiral allenamides lead to chiral nitrogen-stabilized oxyallyl catioins that undergo highly stereoselective (4 + 3) cycloaddition reactions with electron-rich dienes.6 These are the first examples of epoxidations of allenes, and the first examples of chiral nitrogen-stabilized oxyallyl cations. Further elaboration of the cycloadducts leads to interesting chiral amino alcohols that can be useful as ligands in asymmetric catalysis (Scheme 2). 

Dimethoxyethylacrylate (94) may be readily converted into the cationic species 95 by the action of Lewis acids [92] (Equation 3.32) the cationic species then undergoes Diels Alder reaction with a variety of dienes. The type of catalyst markedly affects the reaction yield, stereoselectivity and regioselectivity as shown in Scheme 3.19 and Equation 3.33. 

Keywords cationic Diels-Alder reaction, asymmetric synthesis, stereoselective Diels-Alder reaction... 

Most of these results have been obtained in methanol but some of them can be extrapolated to other solvents, if the following solvent effects are considered. Bromine bridging has been shown to be hardly solvent-dependent.2 Therefore, the selectivities related to this feature of bromination intermediates do not significantly depend on the solvent. When the intermediates are carbocations, the stereoselectivity can vary (ref. 23) widely with the solvent (ref. 24), insofar as the conformational equilibrium of these cations is solvent-dependent. Nevertheless, this equilibration can be locked in a nucleophilic solvent when it nucleophilically assists the formation of the intermediate. Therefore, as exemplified in methylstyrene bromination, a carbocation can react 100 % stereoselectivity. 

However, a number of examples have been found where addition of bromine is not stereospecifically anti. For example, the addition of Bf2 to cis- and trans-l-phenylpropenes in CCI4 was nonstereospecific." Furthermore, the stereospecificity of bromine addition to stilbene depends on the dielectric constant of the solvent. In solvents of low dielectric constant, the addition was 90-100% anti, but with an increase in dielectric constant, the reaction became less stereospecific, until, at a dielectric constant of 35, the addition was completely nonstereospecific.Likewise in the case of triple bonds, stereoselective anti addition was found in bromination of 3-hexyne, but both cis and trans products were obtained in bromination of phenylacetylene. These results indicate that a bromonium ion is not formed where the open cation can be stabilized in other ways (e.g., addition of Br+ to 1 -phenylpropene gives the ion PhC HCHBrCH3, which is a relatively stable benzylic cation) and that there is probably a spectrum of mechanisms between complete bromonium ion (2, no rotation) formation and completely open-cation (1, free rotation) formation, with partially bridged bromonium ions (3, restricted rotation) in between. We have previously seen cases (e.g., p. 415) where cations require more stabilization from outside sources as they become intrinsically less stable themselves. Further evidence for the open cation mechanism where aryl stabilization is present was reported in an isotope effect study of addition of Br2 to ArCH=CHCHAr (Ar = p-nitrophenyl, Ar = p-tolyl). The C isotope effect for one of the double bond carbons (the one closer to the NO2 group) was considerably larger than for the other one. ... 

Norbomyl cations, besides displaying the 1,2 shifts of a CH2 group previously illustrated for the isobomeol —> camphene conversion, are also prone to rapid hydride shifts from the 3 to the 2 position (known as 3,2 shifts). These 3,2 shifts usually take place from the exo side, that is, the 3-exo hydrogen migrates to the 2-exo position. This stereoselectivity is analogous to the behavior we have previously... 

Substituted 1,2,3,4-tetrahydroquinolines (e.g., 61) are formed with high regio- and stereoselectivity in high yield by intermolecular [A+2] cycloadditions of cationic 2-aza-butadienes and various dienophiles <95CC2137,96SL34>. 

Cyclopenta[fc]dioxanes (44) are accessible from the reaction of the dioxenylmolybdenum carbene complex (43) with enynes <96JOC159>, whilst an intramolecular and stereoselective cyclisation of (Ti5-dienyl)tricarbonyliron(l+) cations affords chiral frans-2,3-disubstituted 1,4-dioxanes <96JOC1914>. 2,3-Dimethylidene-2,3-dihydro-1,4-benzodioxin is a precursor of the 3,8-dioxa-lff-cyclopropa[i]anthracene, which readily dimerises to dihydrotetraoxaheptacene (45) and the analogous heptaphene <96AJC533>. 

Many chemical reactions and processes yield cationic racemic products, and either a resolution or a stereoselective synthesis must be envisaged to obtain the chiral cations in an enantioenriched or enantiopure form. Resolution has been strongly studied [130] and selected representative examples of such processes mediated by chiral P( VI) anions are presented. 

For cations 74-75 (Fig. 27), low temperature NMR experiments were necessary to reveal stereodynamical behaviors and allow the observation of split signals for the enantiomers [38,144]. Stereoselective recognition between the chiral cations and anions was observed in essentially all cases as integration of the split signals revealed the preferential occurrence of one diastereomeric salt over the other. 

An explanation was suggested for these solvent and support effects and this is represented in Fig. 19. Thus, in solvents with greater dielectric permittivity, e, the cationic complex is situated further from the clay surface and the stereoselectivities are therefore more similar to those obtained in homogeneous phase. On the other hand, in solvents with low e, close ion pairs are formed and the surface has a larger effect on the reaction. 

Chiral-at-metal cations can themselves serve as chirality inducers. For example, optically pure Ru[(bipy)3] proved to be an excellent chiral auxihary for the stereoselective preparation of optically active 3D anionic networks [M(II)Cr(III)(oxalate)3]- n (with M = Mn, Ni), which display interesting magnetic properties. In these networks all of the metalhc centers have the same configuration, z or yl, as the template cation, as shown by CD spectroscopy and X-ray crystallography [43]. 

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