Asymmetrical alkenes, electrophilic addition

Markovnikov s rule the actual rule is When a hydrogen habde adds to an asymmetrical alkene, the addition occurs such diat the halogen attaches itself to die carbon of the alkene bearing die lowest number of hydrogen atoms. A more universal rule is The electrophile adds to die sjp- carbon that is bonded to die greater number of hydrogens. ... 

Electron-deficient alkenes generally require the use of some other epoxidation procedure, owing to their low reactivity under electrophilic addition conditions. Within this categoiy, o,P-unsaturated ketones tend to be the substrates of interest, and basic oxygen transfer reagents are fiequently encountered, such as HjOj/NaOH, t-BuOOH/NaOH, and NaOCl. Much activity has centered around the modification of these traditional conditions to accommodate asymmetric induction. In this regard, variously substituted Cinchona alkaloids (e.g., 39 - 41) have received a fair amount of attention over the past year. 

Among the transition-metal catalysts that have been used, only those of Pd(II) are productive with diazomethane, which may be the result in cyclopropanation reactions [7,9,21] of a mechanism whereby the Pd-coordinated alkene undergoes electrophilic addition to diazomethane rather than by a metal carbene transformation in any case, asymmetric induction does not occur by using Pd(II) complexes of chiral bis-oxazolines [22],... 

Electron-deficient carbenium ions interact not only with n-donors but also with other electron-rich compounds, including alkenes, alkynes, and aromatic rings. For example, vinyl monomers and polymer chains may complex carbenium ions. Electrophilic addition (propagation) may proceed by Jl-complexation as in the asymmetric complex (C ) shown in Eq. 14. 

A number of useful enantioselective syntheses can be performed by attaching a chiral auxihary group to the selenium atom of an appropriate reagent. Examples of such chiral auxiliaries include (49-53). Most of the asymmetric selenium reactions reported to date have involved inter- or intramolecular electrophilic additions to alkenes (i.e. enantioselective variations of processes such as shown in equations (23) and (15), respectively) but others include the desymmefrization of epoxides by ringopening with chiral selenolates, asymmetric selenoxide eliminations to afford chiral allenes or cyclohexenes, and the enantioselective formation of allylic alcohols by [2,3]sigmafropic rearrangement of allylic selenoxides or related species. 

Synthesis of a chiral compormd from an achiral compound requires a prochiral substrate that is selectively transformed into one of the possible stereoisomers. Important prochiral substrates are, for example, alkenes with two different substituents at one of the two C-atoms forming the double bond. Electrophilic addition of a substitutent different from the three existing ones (the two different ones above and the double bond) creates a fourth different substituent and, thus, an asymmetric carbon atom. Another class of important prochiral substrates is carbonyl compounds, which form asymmetric compounds in nucleophilic addition reactions. As exemplified in Scheme 2.2.13, prochiral compounds are characterized by a plane of symmetry that divides the molecule into two enantiotopic halves that behave like mirror images. The side from which the fourth substituent is introduced determines which enantiomer is formed. In cases where the prochiral molecule already contains a center of chirality, the plane of symmetry in the prochiral molecules creates two diastereotopic halves. By introducing the additional substituent diasterom-ers are formed. 

In contrast to a, -ethylenic ketones or even a, -ethylenic sulfones, a, ) -ethylenic sulfoxides generally are not sufficiently electrophilic to undergo successful nucleophilic j8-addition . a-Carbonyl-a, j8-ethylenic sulfoxides, however, are potent, doubly activated alkenes which undergo rapid and complete -addition of various types of nucleophiles even at — 78 °C. A brief account summarizing this area is available . The stereochemical outcome of such asymmetric conjugate additions to enantiomerically pure 2-sulfmyl 2-cycloalkenones and 2-sulfinyl-2-alkenolides has been rationalized in terms of a metal-chelated intermediate in which a metal ion locks the -carbonyl sulfoxide into a rigid conformation (36 cf. 33). In this fixed conformation, one diastereoface of the cyclic n... 

The mechanism of the asymmetric methoxyselenenylation of alkenes has been investigated using competition experiments and computational methods (Scheme 8). The experiments have demonstrated that the formation of the intermediate seleniranium ion (48) is reversible. Ions of type (49), generated in the addition of chiral selenium electrophiles to alkenes, are the key intermediates in the asymmetric methoxyselenenylation their stability is strongly dependent on the strength of the selenium-heteroatom interaction. Calculations have been carried out to determine the relative stabilities of the diastereoisomeric seleniranium ions (49). The results obtained from the calculations support the experimental flndings. ... 

Asymmetric conjugate addition to a variety of electrophilic alkenes using chiral organolithium-ligand complexes are summarized in Table 10. The complexes 34 and 35 prefer... 

Michael-aldol reaction as an alternative to the Morita-Baylis-Hillman reaction 14 recent results in conjugate addition of nitroalkanes to electron-poor alkenes 15 asymmetric cyclopropanation of chiral (l-phosphoryl)vinyl sulfoxides 16 synthetic methodology using tertiary phosphines as nucleophilic catalysts in combination with allenoates or 2-alkynoates 17 recent advances in the transition metal-catalysed asymmetric hydrosilylation of ketones, imines, and electrophilic C=C bonds 18 Michael additions catalysed by transition metals and lanthanide species 19 recent progress in asymmetric organocatalysis, including the aldol reaction, Mannich reaction, Michael addition, cycloadditions, allylation, epoxidation, and phase-transfer catalysis 20 and nucleophilic phosphine organocatalysis.21... 

The chiral anisole derivative 37 has been used in the synthesis of several asymmetric functionalized cyclohexenes (Table 9) [22]. In a reaction sequence similar to that employed with racemic anisole complexes, 37 adds an electrophile and a nucleophile across C4 and C3, respectively, to form the cyclohexadiene complex 38. The vinyl ether group of 38 can then be reduced by the tandem addition of a proton and hydride to C2 and Cl, respectively, affording the alkene complex 39. Direct oxidation of 39 liberates cydohexenes 40 and 41, in which the initial asymmetric auxiliary is still intact. Alternatively, the auxiliary may be cleaved under acidic conditions to afford /y3 -allyl complexes, which can be regioselectively attacked by another nucleophile at Cl. Oxidative decomplexation liberates the cyclohexenes 42-44. HPLC analysis revealed high ee values for the organic products isolated both with and without the initial asymmetric group. 

Well before the wide use of organoselenium compounds in chemistry, it was discovered that electrophilic selenium compounds of the type RSeX add stereospecifically to alkenes.45 Since that time this reaction has been an important tool in the portfolio of organic chemists and has been used even for the construction of complex molecules. Comprehensive reviews on this chemistry have appeared46-49 and in recent times the synthesis of chiral selenium electrophiles and their application in asymmetric synthesis has emerged. As shown in Scheme 1, the addition reactions of selenium electrophiles to alkenes are stereospecific anti additions. They involve the initial formation of seleniranium ion intermediates 1 which are immediately opened in the presence of nucleophiles. External nucleophiles lead to the formation of addition products 2. The addition to unsymmetrically substituted alkenes follows the thermodynamically favored Markovnikov orientation. The seleniranium ion intermediates of alkenes with internal nucleophiles such as 3 will be attacked intramolecularly to yield cyclic products 4 and 5 via either an endo or an exo pathway. Depending on the reaction conditions, the formation of the seleniranium ions can be reversible. 

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