Stereospecificity halogenation

Keywords cholesterol ester, stereospecific halogenation, waste-free, gas-solid reaction... 

Reaction proceeds in the presence of pyridine, but in some cases the ben-zotriazole anion, formed in the course of the reaction, acts as a base. Reaction is stereospecific halogenation of compounds with a prochiral a-carbon yields only one of two possible diastereoisomers. Chlorination of optically active sulfoxides takes place with preservation of configuration, but addition of silver ions causes the inversion of configuration at sulfur. The lability of hydrogen at the a-carbon atom does not considerably affect the direction of chlorination. On chlorination of benzyl methyl sulfoxide, benzyl chloromethyl and a-chlorobenzyl methyl derivatives are formed in approximately equal amounts (Scheme 66). 

A detailed investigation of the stereochemistry of cis- and tran5-[RuCl2(L-L)2] (l L = o-QH< (EMePh)2 E = As, P) has been undertaken. The optically active, racemic, meso, syn, and anti forms of the trans compound were isolated for both ligands each of these subsequently isomerized to the corresponding cis complex by reaction with AlEts and the various diastereoisomers of the latter separated and characterized. Whereas the trans isomers are relatively inert, the cis complexes readily undergo stereospecific halogen substitution by 1 and A minor product obtained... 

SCHEME 43.2. Early stage installation of halogens via stereospecific halogenation of epoxides. 

SCHEME 43.3. Late-stage halogenation via stereospecific halogenation of cyclic aUcanols. 

Addition of halogens (Sections 6 14-6 16) Bromine and chlorine add to alkenes to form vicinal dihalides A cy clic halonium ion is an intermediate Stereospecific anti addition is observed... 

Some of the newer compounds may contain both saturated and unsaturated rings, heteroatoms such as oxygen, nitrogen, or sulfur, and halogen substituents. Others, such as synthetic pyrethroids, may have one or more chiral centers, often needing stereospecific methods of synthesis or resolution of isomers (42). Table 4 Hsts examples of some more complex compounds. Stmctures are shown ia Eigure 1 (25). 

The introduction of halogen into organic molecules can be carried out by a variety of addition or substitution reactions. The classical methods for the addition of halogen to double bonds or the substitution of halogen for hydroxyl by hydrohalic acids are too well known to bear repetition here. Discussed below, then, are methods that are of interest because of their stereospecific outcome or because they may be used on sensitive substrates. 

Halogen atoms can be stereoselectively introduced by ring-opening of y-azir-idinyl-a,P-enoates (Scheme 2.39). Treatment of 149 with diethylaminosulfur tri-fluoride (DAST) results in stereospecific ring-opening to yield fluorinated derivative 150 [59]. A related stereoselective conversion of y-aziridinyl-a,P-enoates 151 into allyl halides 152 by use of lithium halide in the presence of Amberlyst 15 was also reported recently [60]. 

Stereospecificity of this reaction reaches 15 1 for telomer T3. Telomer T3 is a crystalline product, this allowed the authors to use X-ray diffraction analysis for studying stereochemistry. Stereoselectivity observed in the formation of T3 shows that both addition step and the step of halogen transfer to the growing radical proceed stereoselectively in this case. 

The 2+2 cycloadditions of benzyne to cis- and trani-propenyl ether gave cis- and fran -benzocyclobntanes as the main products, respectively [ 117,118], Stereospecific [2+2] cycloaddition reactions were observed between the benzyne species generated by the halogen-Uthium exchange reaction of ort/io-haloaryl triflates and the ketene silyl acetals (Scheme 23) [119],... 

Itoh N, AKM Quamrul Hasan, Y Izumi, H Yamada (1988) Substrate specificity, regiospecificity and stereospecificity of halogenation reactions catalyzed by non-heme-type bromoperoxidase of Corallina pilulifera. Eur J Biochem 172 477-484. 

Because of its high reactivity, special precautions must be taken with reactions of fluorine and its use is somewhat specialized.44 Nevertheless, there is some basis for comparison with the less reactive halogens. Addition of fluorine to Z- and E-1-propenylbenzene is not stereospecific, but syn addition is somewhat favored.45 This result is consistent with formation of a cationic intermediate. 

Positive halogen reagents can cyclize y- and 8-hydroxyalkenes to tetrahydro-furan and tetrahydropyran derivatives, respectively.85 Iodocyclization of homoal-lylic alcohols generates 3-iodotetrahydrofiirans when conducted in anhydrous acetonitrile.86 The reactions are stereospecific, with the /(-alcohols generating the irons and the Z-isomer the cis product. These are endo-5 cyclizations, which are preferred to exo-4 reactions. 

In method (ii), the group X (e.g., a halogen) may function as a three-electron donor when present as a bridging group, but as a one-electron donor when combined to one metal center. The simple act of bridgeopening creates a vacant coordination site on one metal atom. Behavior of this sort is invoked to explain the stereospecific incorporation of I3CO in the complex Os3(CO)10Cl2. 

For the dibridged species, such as the halogen derivatives HOs2(CO)i0X (X = Cl, Br), we have used this type of behavior to explain the stereospecific incorporation of, 3CO into the molecules (160). The halogen group varies from a three-electron donor in bridged molecules to a one-electron donor in the terminally bonded species. 

The mechanism for the addition of 50 to anthraquinone (Scheme 52), 1,4-diacetylbenzene (Scheme 53), and 1,2-diacetylbenzene (Scheme 54) has been proposed.326 The addition of 50 to benzophenone followed by reaction with Wilkinson s catalyst formally results in the hydrogenation of a double bond (Equation (262)).325 This species also undergoes stereospecific inertion into the vinyl chloride bond of various halogenated alkenes with high yields in most cases (Equations (263)-(267)).329... 

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