A Novel Entry to 17α-Bromo- and 17α-Iodoethynyl Steroids

Publisher Summary This chapter discusses properties, structures, and reactivity of manganese redox enzymes and model systems. Manganese is one of several first-row transition elements that are employed by biological systems to assist in varied metabolic and structural roles. Manganese is used to give structural support to proteins and is a cofactor in chemical transformations that include hydrolytic and redox reactions. Perhaps the best-known function, and the one of great importance to aerobic life, is in the oxygen-evolving complex, which oxidizes water to dioxygen during photosynthesis. The discussions of data gathering on enzyme systems and model chemistry, both structural and functional, presented in this chapter provides a foundation for exploring current and as yet undiscovered manganese enzymes. The biological applications of manganese are numerous and quite varied. The manganese-containing redox enzymes are unique. Most of these deal with dioxygen metabolism in one form or another.

Manganese Redox Enzymes and Model Systems: Properties, Structures, and Reactivity

Although recent years have witnessed significant advances in the development of catalytic, enantioselective halofunctionalizations of alkenes, the related dihalogenation of olefins to afford enantioenriched vicinal dihalide products remains comparatively underdeveloped. However, the growing number of complex natural products bearing halogen atoms at stereogenic centers has underscored this critical gap in the synthetic chemist's arsenal. This Review highlights the selectivity challenges inherent in the design of enantioselective dihalogenation processes, and formulates a mechanism-based classification of alkene dihalogenations, including those that may circumvent the "classical" haliranium (or alkene-dihalogen π-complex) intermediates. A variety of metal and main group halide reagents that have been used for the dichlorination or dibromination of alkenes are discussed, and the proposed mechanisms of these transformations are critically evaluated.

Catalytic, Stereoselective Dihalogenation of Alkenes: Challenges and Opportunities.

Oxidation of alcohols by hydrogen peroxide is negligible; even when catalyzed by methyltrioxorhenium (MTO), the process requires a long reaction time. The addition of a catalytic quantity of bromide ions, as HBr or NaBr, greatly enhances the rate. Some of the reactions were carried out on a larger scale in glacial acetic acid, and others at kinetic concentrations. The data establish that Br2 is the active oxidizing agent in the system, because the catalytic rates under suitable circumstances match those for the independently measured Br2 reaction with alcohol (benzyl alcohol, in particular). At much lower levels of MTO, however, Br2 formation plays a role in the kinetics. Certain other reluctant transformations are conveniently carried out with the MTO/H2O2/Br- combination:  aldehydes to methyl esters; 1,3-dioxolanes to glycol monoesters; and ethers (with cleavage) to ketones (mostly), but in fair yield only. When Br- was used in stoichiometric quantity, certain bromination reactions occur. Thus, phenyl a...

Bromide Ions and Methyltrioxorhenium as Cocatalysts for Hydrogen Peroxide Oxidations and Brominations

Regioselective thiocyanation of aromatic and heteroaromatic compounds using ammonium thiocyanate and oxone

Reactions of acetylenes (RCCR′; R and/or R′= H, alkyl, or phenyl)(1), with copper(II) chloride–lithium chloride in acetonitrile give the corresponding E-dichloroalkenes in good yields except in the case of (1; R = Ph, R′= But) where the Z-product is favoured. Reactions with copper(II) chloride–iodine or –potassium iodide proceed more smoothly to afford, completely regiospecifically and highly stereospecifically, E-chloroiodoalkenes in high yields. Reactions with iodine chloride also give the same compounds, but the yield and E-stereospecificity are low in comparison with those in the copper(II) chloride–iodine case. An open vinyl cation intermediate in which copper(I) co-ordinates weakly with both the double bond and the chlorine atom attached to carbon is postulated for chlorination, and a cyclic iodonium ion intermediate is proposed for chloroiodination.

Chlorination and chloroiodination of acetylenes with copper(II) chloride

Reactions of acetylenes (RCCR′: R and/or R′= H, alkyl, or phenyl)(1) with molecular bromine in chloroform give a mixture of the corresponding E- and Z-dibromoalkenes in high yields, the E-isomer being predominant under kinetically controlled conditions except in the case of (1; R = Ph, R′= But) where the Z-isomer is the sole product. From the reaction with an excess of bromine or under u.v. irradiation a thermodynamic equilibrium mixture of both isomers was obtained, the same mixture being readily formed by u.v. irradiation of a solution of any mixture of isomers in chloroform. Reactions with copper(II) bromide in acetonitrile at 20–25 °C also give the same products, the rates of reacton being much less and the isomerization of the products much slower, and the stereospecificity being much higher than for bromination with molecular bromine. The kinetically controlled product ratios between E- and Z-dihalogenoalkenes are obtained from the reactions of four alkylphenylacetylenes (R = Ph, R′= H, Me, Pri, or But) with iodine, iodine monochloride, bromine, and chlorine. The results are explained in terms of a cyclic iodonium ion intermediate for the former two reactions and an open vinyl cation intermediate for the last; for bromination, an open vinyl cation intermediate in which bromine may interact weakly with the benzylic carbon is postulated.

Stereochemistry of the bromination of acetylenes with bromine and copper(II) bromide

Alkyl- and halobenzenes give thiocyano-derivatives when treated with a mixture of SbCl5 and Pb(SCN)2 in CCl4. The reaction proceeds via in situ formation of ClSCN from SbCl5 and Pb(SCN)2 followed by its attack on aromatic compounds catalyzed by SbCl5, the reaction species being SCN+SbCl6−.

Aromatic Thiocyanation by a Mixture of Antimony(V) Chloride and Lead(II) Thiocyanate

The chlorination of 1,3-cyclooctadiene with various chlorinating agents gave an isomeric mixture of trans-3,4-, cis-3,4-, trans-3,8-, and cis-3,8-dichlorocyclooctene. From 1,5-cyclooctadiene an isomeric mixture of trans- and cis-5,6-dichlorocyclooctene was obtained. The isomer distribution depended a great deal on chlorinating agents in both cases.

The Chlorination of 1,3- and 1,5-Cyclooctadienes with Various Chlorinating Agents

The reactions of acetylenes with bromine in alcohols at 20–25 °C afford dibromodialkoxyalkanes in good yields together with variable amounts of dibromoalkenes. Similar treatment of phenylacetylene with copper(II) bromide gives only bromophenylacetylene and 2-phenyl-1,1,2-tribromoethylene, the latter being formed by dibromination of the former with copper(II) bromide.

Hajime Okazaki

Papers

Chlorination and chloroiodination of acetylenes with copper(II) chloride

Stereochemistry of the bromination of acetylenes with bromine and copper(II) bromide

Aromatic Thiocyanation by a Mixture of Antimony(V) Chloride and Lead(II) Thiocyanate

The Chlorination of 1,3- and 1,5-Cyclooctadienes with Various Chlorinating Agents

Solvent Incorporation in Bromination of Acetylenes in Alcohols