Dihalo-addition

Halogenation of Double and Triple Bonds (Addition of Halogen, Halogen) Dihalo-addition... 

Carbenes, addition to multiple bonds, 61 addition to olefins, 59, 60 analogy with carbonium ions, 60 co-ordination reactions of, 61 dibromo-, see dihalocarbenes dichloro-, see dihalocarbenes dihalo-, addition to olefins, 59, 61 dihalo-, deoxygenation of aromatic N-oxides by, 77... 

Treatment of geminal dihalocyclopropyl compounds with a strong base such as butyl lithium has been for several years the most versatile method for cumulenes. The dihalo compounds are easily obtained by addition of dihalocarbenes to double--bond systems If the dihalocyclopropanes are reacted at low temperatures with alkyllithium, a cyclopropane carbenoid is formed, which in general decomposes above -40 to -50°C to afford the cumulene. Although at present a number of alternative methods are available , the above-mentioned synthesis is the only suitable one for cyclic cumulenes [e.g. 1,2-cyclononadiene and 1,2,3-cyclodecatriene] and substituted non-cyclic cumulenes [e.g. (CH3)2C=C=C=C(CH3)2]. 

In addition to the trialkyldihalo- and triaryldihalo antimony compounds, mixed dihalo compounds such as chi oroiodo triphenyl antimony [7289-82-9], (CgH3)2SbClI, have been reported (182). It has been shown, however, that such compounds disproportionate ia solutioa to give a mixture of startiag material plus products (183) ... 

Addition to the Double Bond. Chlorine, bromine, and iodine react with aHyl chloride at temperatures below the inception of the substitution reaction to produce the 1,2,3-trihaLides. High temperature halogenation by a free-radical mechanism leads to unsaturated dihalides CH2=CHCHC1X. Hypochlorous and hypobromous acids add to form glycerol dihalohydrins, principally the 2,3-dihalo isomer. Dehydrohalogenation with alkah to epicbl orobydrin [106-89-8] is ofgreat industrial importance. 

During the preparation of the dihalo-(usually dibromo) 20-ketopregnanes, other reactive sites must be protected (e.g., addition of bromine to the A -double bond, ketal formation with a 3-ketone). An elegant method which avoids such problems has been devised by the Upjohn group in their studies on the conversion of 11-ketoprogesterone to hydrocortisone. The former is reacted with ethyl oxalate at C-2 and C-21, then addition of three moles of bromine gives a 2,21,21-tribromide. Alkaline rearrangement produces the side chain unsaturated acid, and the bromine at C-2 is subsequently removed with zinc. 

As a final example in this section, a contribution by Grubbs et al. is discussed. The chloride-free ruthenium hydride complex [RuH2(H2)2(PCy3)2] (37) is believed to react, in the presence of alkenes, to form an unidentified ruthenium(O) species which undergoes oxidative additions with dihalo compounds, e.g., 38, to give the corresponding ruthenium carbene complex 9 (Eq. 4) [20]. 

Other sources of Ru(0) can also be used for this synthesis. For example, it was recently demonstrated that [Ru(arene)(diene)] complexes such as 39 undergo double oxidative addition of heterosubstituted dihalo compounds 40 in the presence of phosphine ligands (Eq. 5) [21]. 

The catalytic conditions (aqueous concentrated sodium hydroxide and tetraalkylammonium catalyst) are very useful in generating dihalo-carbenes from the corresponding haloforms. Dichlorocarbene thus generated reacts with alkenes to give high yields of dichlorocyclopropane derivatives,16 even in cases where other methods have failed,17 and with some hydrocarbons to yield dicholromethyl derivatives.18 Similar conditions are suited for the formation and reactions of dibromocar-benc,19 bromofluoro- and chlorofluorocarbene,20 and chlorothiophenoxy carbene,21 as well as the Michael addition of trichloromethyl carbanion to unsaturated nitriles, esters, and sulfones.22... 

In contrast, synthesis of 3,4-diphosphorylthiophenes requires more elaboration because of low reactivity of 3,4-positions of thiophene and unavailability of 3,4-dihalo or dimetallated thiophenes. Minami et al. synthesized 3,4-diphosphoryl thiophenes 16 as shown in Scheme 24 [46], Bis(phosphoryl)butadiene 17 was synthesized from 2-butyne-l,4-diol. Double addition of sodium sulfide to 17 gave tetrahydrothiophene 18. Oxidation of 18 to the corresponding sulfoxide 19 followed by dehydration gave dihydrothiophene 20. Final oxidation of 20 afforded 3,4-diphosphorylthiophene 16. 3,4-Diphosphorylthiophene derivative 21 was also synthesized by Pd catalyzed phosphorylation of 2,5-disubstituted-3,4-dihalothiophene and converted to diphosphine ligand for Rh catalysts for asymmetric hydrogenation (Scheme 25) [47],... 

Addition of halogens and pseudohalogens to the cyclopropylthiocarbene chromium complexes 122 affords the 1,4-dihalo-1-phenylthio-l-alkenes 123 stereoselectively [65]. Electrophilic halogen is likely to activate the carbene complexes, followed by the homo-Michael addition of halide anion. (Scheme 44)... 

This concerted process may operate in the case of d° early metal complexes where the oxidative addition is forbidden [194]. Nevertheless, it was postulated also in the interaction of a dihalo-ruthenium(II) intermediate and a hydrosilane... 

The glycals are easily converted into the 1,2-dihalo-derivatives, which in principle can act as glycosyl donors. However, these derivatives have not found wide application in glycoside synthesis, mainly because of the low facial selectivity in the initial addition of the electrophilic species [143-145]. In an example of a successful application, 2-deoxy-2-bromo-a-D-glucopyranosyl bromide [146] has been shown to give predominantly the 2-deoxy-P-D-glucopyranosides in silver-triflate-promoted reactions with alcohols. 

The electrophilic addition of Br2 or Cl2 to 2,3-butadiene nitrile afforded 3,4-dihalo-2-butenenitriles [261]. 

Although chlorination, bromination and iodination of thiophenes by polyhalide salts require forcing conditions with the addition of zinc chloride [52], halogenation of acridine and acridone has been recorded to yield both 3-halo and 3,7-dihalo derivatives under relatively mild reaction conditions [53], However, whereas chloro-, bromo- and iodo-compounds are readily obtained from acridone, acridine only forms the bromo derivatives, as it produces stable complexes with the dichloroiodate and tetrachloroiodate salts [53]. 

However, this process requires a reaction time of 2 days and is inapplicable to unsymmetrical couplings (two different epoxides). As the study described in equation 24 revealed a dramatic solvent effect on similar Brook isomerizations in the adduct of lithio dihalo(triaIkylsilyl)methanes with epoxides (isomerization did not occur following metalation and initial alkylation in THF but proceeded readily upon addition of HMPA), the effect of HMPA for promoting the Brook isomerization was studied once the first alkylation was complete (equation 28) . ... 

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