Dehalogenation stereoselective

Abstract Recent advances in the metal-catalyzed one-electron reduction reactions are described in this chapter. One-electron reduction induced by redox of early transition metals including titanium, vanadium, and lanthanide metals provides a variety of synthetic methods for carbon-carbon bond formation via radical species, as observed in the pinacol coupling, dehalogenation, and related radical-like reactions. The reversible catalytic cycle is achieved by a multi-component catalytic system in combination with a co-reductant and additives, which serve for the recycling, activation, and liberation of the real catalyst and the facilitation of the reaction steps. In the catalytic reductive transformations, the high stereoselectivity is attained by the design of the multi-component catalytic system. This article focuses mostly on the pinacol coupling reaction. 

Explain the observed stereoselectivity in the following ratfrcal dehalogenation ... 

Similar addition mechanisms explain the so-called halolactonization and the related haloetherification (Figure 3.47). With the help of these reactions one can produce halogenated five- and six-membered ring lactones or ethers stereoselectively. Dehalogenation afterward is possible (Figure 1.38). 

Fig. 3.36. Stereoselective iodolactonization (top) and stereoselective bromoetherification (bottom). See Figure 1.30 for the dehalogenations of the iodolactone and of the bromoether shown.

Stereoselective dehalogenation of 2-haloaIkanoic acids has been demonstrated for a number of halidohydrolases (80-82). Figure 77 details the production of an L-haloacid intermediate used in the production of phen-oxypropionic acid herbicides. The R enantiomer of chloropropionic acid is selectively hydrolyzed to (S)-lactic acid due to an inversion of configuration that occurs during the hydrolysis (83). (S)-2-chloroproprionic acid is used as a chiral synthon to produce a number of (R)-phenoxypropionic acid herbicides, for example, Fusilade 2000 (ICI). 

Halogeno-alkenes.- The photochemical behaviour of AJdrm (30a) is complex. A reinvestigation of the irradiation of this cyclodiene insecticide in hexane has isolated two new photo products (30b) and (31). Irradiation in acetone also provides surprises and the two new adducts (32) and (33) have been identified. The influence of triethylamine on photodehalogenation of cyclodiene insecticides has also been evaluated. Irradiation appears to bring about selective dehalogenation at C-11 in (30a) yielding a 9 1 mixture of the products (34a) and (34b). This stereoselective loss of chlorine is also seen with Dieldrin (35) and Endrin (36). ... 

Addition of Me Al to BusSnH/AIBN-promoted dehalogenation of a-bromo-a-fluoro-/i-hydroxy esters with high stereoselectivity, leading to threo-fluoro-Zi-hydroxy esters, irrespective of stereochemistry of the starting esters (Scheme 12.128) [231]. 

In all cases, hydrochloric acid is formed due to stereoselective dehalogenation of CPD or DCP by the bacteria. Therefore, we have to feed racemic raw materials using a pH-stat system we detect the decline in pH by the hydrochloric acid formed and add NaOHaq to neutralize the reaction mixture, and then more race-mate is added for further reaction (Fig. 6). When the reaction is finished, the % ee of the product should be >99.5-99.8%. The total added racemate should be as high as possible, and the time should be as short as possible. The production efficiency and the final optical purity are essential factors in the plant. The problem is detecting when the final feeding occurs and how much of the racemate is in the production (the fed-cultivation). 

One of the earliest descriptions of an asymmetric lithiating reagent was reported by Nozaki and co-workers in 1968 (35). (—)-Sparteine was used to coordinate n-butyllithium, and this complex stereoselectively added to several carbonyl compounds (Reaction 32). Moreover, the Skattebol-Moore method (which consists of dehalogenating gem-dihalo-cyclopropanes with an alkyllithium complex) by Nozaki to synthesize allenes gave optically active products when the n-butyllithium/ ( —)-sparteine complex was used (36). 

Carbon - heteroatom bonds can be cleaved by an appropriate combination of a hard acid and a soft nucleophile. Synthetically useful selective C-0 bond cleavage in the presence of other C-0 bond(s) is described. Reductive dehalogenation of a-haloketones is presented as an example that illustrates the concept of hard-soft affinity inversion. Finally, regio- and stereoselective functionalization of 1,3-di-enes is demonstrated by the thienium cation Diels-Alder cyclization involving the C-S bond cleavage. 

The mechanisms of dehalogenations have been reviewed by Miller and in a series of papers , the stereoselectivity of the dehalogenation of the stilbene dibromides with a wide variety of reagents has been discussed. The meso-stilbene dibromide always eliminates to give the thermodynamically more stable alkene, namely tra 5-stilbene which is product of apparent a t/-elimina-tion. However, the J/-stilbene dibromide gives both cis- and rm i-stilbenes, and the ratio of these products can provide useful mechanistic information. One-electron reductants, such as chromous ion, give rise to intermediate radical formation in which rotation about the Ca-Cg bond allows thermodynamic control of the reaction. Two-electron reductants, such as iodide ion in dimethyl formamide, induce highly stereoselective a i-elimination. In protic solvents, carbonium ion intermediates were proposed to explain the trend towards thermodynamic control. Miller has proposed a reaction mechanism which embraces elimination, substitution, and electrophilic addition to alkenes. 

Good stereoselectivity is observed when 3-phenylalk-5-en-l-ols (7) are cyclised by electrophilic halogen reagents, leading to single diastereoisomers of 2,4-disubstituted tetrahydropyrans upon reductive dehalogenation. Cyclisation of the epoxides derived from the alkenol is also stereospecific <97TL6449>. 

Readily available /3-hydroxy-esters (e.g. 49) can be converted into butyrolactones (e.g. 50) simply by treatment with concentrated sulphuric acid. Cyclic ether-lactones (52) are available from hydroxy-acids (51) by iodolactonization followed by dehalogenation with silver acetate. A stereoselective total synthesis of the antifungal mould metabolite (53) has been reported. ... 

In the dehalogenation reactions, ILs used for debromination can be achieved by using a metal like Zn, Mg, or In, in an organic solvent, such as tetrahydrofuran (THF) or methyl alcohol (MeOH). Ranu et al. [21, 22] reported that IL [pmim] [BFJ can be used as a catalyst as well as a reaction medium for the stereoselective debromination of vicinal dibromides to the corresponding ( )-alkenes under MW irradiation. 

---