Stereoselective Halogenations

Room-temperature ionic liquids may be used as green recyclable alternatives to chlorinated solvents for stereoselective halogenation.577 The bromination of alkenes and alkynes in [bmim][Br] is a/m -stereospecific, whereas that of 1,3-dienes gives selectively the 1,4-addition products. The reactions of arylacetylenes, however, are not selective when carried out in [bmim][PF6]. Tetraethylammonium trichloride, a stable crystalline solid may be used in the chlorination of alkenes and alkynes to afford the products with exclusive anti stereoselectivity.578 It has... 

Several alkynols reacted with elemental iodine (or NIS, or NBS) assisted by HTI - in either stoichiometric or catalytic amounts - to afford stereoselectively halogenated enones or enals. Examples of such transformations, some of which involved ring-expansion, are given in Table 7.2 a procedure follows. 

Other current investigations concerning cycloadditions of nitrosoalkenes are directed towards employment of more complex dienophiles, e. g. NjM-bis-tri-methylsilyl enamines [380, 381] or 2,5-dihydrooxepines [382]. Furthermore, interest focuses on exploring the scope of subsequent reactions of the cycloadducts, such as stereoselective halogenation [383], ds-dihydroxylation [384] and numerous reductive [385] as well as acid or transition metal induced [386] transformations of 5,6-dihydro-4H-l,2-oxazines. 

Selenium and tellurium reagents have been used for stereoselective halogenations of alkenes. For example, trans addition of benzeneselenenyl chloride to alkenes followed by the displacement of the seleno moie with chloride can lead to dr-1,2-dichlorides (equation 25). The addition of 2-naph-thyltellurium trichloride proceeds in an anti stereospecific manner (equation 26), whereas tellurium tetra-diloride gives a mixture of syn and anti adducts. The reaction of allyl esters with tellurium tetrachloride accompanies acyl migration to give the l-(trichloiottlluro)-3-chk>io adduct (54 equation 27). ... 

The stereoselective tram addition of sulfenyl halides and other sulfenyl derivatives to alkenes can be rationalized by assuming a bridged thiiranium ion, by analogy with the mechanism proposed for stereoselective halogenation of alkenes. 

Chiappe, C., Capraro, D., Conte, V and Pieraccini, D., Stereoselective halogenations of alkenes and allqnies in ionic liquids, Org. Lett. 3,1061-1063 (2001). 

While a simple convincing explanation is not trivial in this case and may even demand a change of the mechanism, the stereoselective halogen metal exchange at the trifluoromethyl substituted double bond of dibromide 663 could be due to lithiumfluor interaction [258]. 

Enzymatic reactions " and electrolysis have also been applied in the stereoselective halogenation but are limited to specific substrates. Generally, these approaches are based on the use of an electrophilic halogen source or an anionic halide nucleophile. For the approaches that use electrophilic halogen sources, the formation of a halonium intermediate is the key to stereochemical control. A subsequent nucleophilic attack of the halonium intermediate typically yields a product with an anti-relationship (Scheme 42.1). 

In this chapter, the applications of stereoselective halogenations (C—Cl, C—Br, and C—I) in the total synthesis of natural or bioactive organohalogens will be shown. The main focus of this chapter will be on the enantioselective synthesis of natural products and bioactive molecules... 

In the history of syntheses of halogen-containing molecules, an early approach to effect the stereoselective halogenation is via substrate control. This section will describe various substrate-controlled stereoselective halogenations found in natural product synthesis. 

Another good strategy for the stereoselective halogenation is via the epoxide ring opening to afford a chiral halohydrin (Scheme 42.14). 

Reagent-controlled stereoselective halogenation refers to the use of a stoichiometric amount of promoter to induce the stereoselective halogenation. To date, the reagent-controlled approaches have hmited examples in the synthesis of chiral bioactive organohalogens and related skeletons. Some recent examples will be described in this section. 

This compilation embraces a wide variety of subjects, such as solid-phase and microwave stereoselective synthesis asymmetric phase-transfer asymmetric catalysis and application of chiral auxiliaries and microreactor technology stereoselective reduction and oxidation methods stereoselective additions cyclizations metatheses and different types of rearrangements asymmetric transition-metal-catalyzed, organocatalyzed, and biocatalytic reactions methods for the formation of carbon-heteroatom and heteroatom-heteroatom bonds like asymmetric hydroamina-tion and reductive amination, carboamination and alkylative cyclization, cycloadditions with carbon-heteroatom bond formation, and stereoselective halogenations and methods for the formation of carbon-sulfur and carbon-phosphorus bonds, asymmetric sulfoxidation, and so on. 

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