Dehydrohalogenation preferential

Primary and secondary alkyl haUdes react well, but alkyl haUdes ate preferentially dehydrohalogenated by the tin reagents. 

We have previously seen (Scheme 2.9, enby 6), that the dehydrohalogenation of alkyl halides is a stereospecific reaction involving an anti orientation of the proton and the halide leaving group in the transition state. The elimination reaction is also moderately stereoselective (Scheme 2.10, enby 1) in the sense that the more stable of the two alkene isomers is formed preferentially. Both isomers are formed by anti elimination processes, but these processes involve stereochemically distinct hydrogens. Base-catalyzed elimination of 2-iodobutane affords three times as much -2-butene as Z-2-butene. 

No extensive investigation of mechanism has been undertaken for any of the methods of dehydrohalogenation described. 17-Bromo-20-ketones appear to undergo preferential /ran -elimination. 2-Halo-3-ketones suffer predominant loss of the la (axial) hydrogen, but the geometry of bromine loss is not known. 7>fl -diaxial elimination has sometimes been assumed in configurational assignments, but this is not necessarily correct (see ref. 6). 

Formal isomerization of the double bond of testosterone to the 1-position and methylation at the 2-position provides yet another anabolic/androgenic agent. Mannich condensation of the fully saturated androstane derivative 93 with formaldehyde and di-methylamine gives aminoketone 94. A/B-trans steroids normally enolize preferentially toward the 2-position, explaining the regiospecificity of this reaction. Catalytic reduction at elevated temperature affords the 2a-methyl isomer 95. It is not at all unlikely that the reaction proceeds via the 2-methylene intermediate. The observed stereochemistry is no doubt attributable to the fact that the product represents the more stable equatorial isomer. The initial product would be expected to be the p-isomer but this would experience a severe 1,3-diaxial non-bonded interaction and epimerize via the enol. Bromination of the ketone proceeds largely at the tertiary carbon adjacent to the carbonyl (96). Dehydrohalogenation... 

In dehydration and dehydrohalogenation the preferential order for removal of an H is 3°>2°> 1 (Saytzeff rule). We can say the poor get poorer. This order obtains because the more R s on the C==C group, the more stable is the alkene. The stability of alkenes in decreasing order of substitution by R is... 

Dehydrohalogenation of 1 //-2-chlorodecafluorocyclohexane (38B) gives products 39 and 21.79 Preferential elimination of hydrogen fluoride occurs in compound 38B, where hydrogen and fluorine are in an antiperiplanar conformation. 

Lee, J. G. Bartsch, R. A. Dehydrohalogenation by complex base (NaNH2/NaOtBu). Preferential loss of poorer halogen leaving groups. 

The literature in the field of controlled ketene cross-dimerization is relatively sparse, with the lack of suitable catalysts to preferentially enable heterodimerization as opposed to homodimerization a recurring problem in establishing a useful synthetic protocol. Sporadic reports of controlled heterodimerization of unusual ketene classes exist in the literature, but are limited to halogenated [64] and cyano-ketenes [65]. Nevertheless, the laboratory of Romo was able to successfully dehydrohalogenate acid chlorides to generate racemic ketene heterodimers used as intermediates in the preparation of salinosporamide A and cinnabaramide A [42b]. 

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