Iodohydrin epoxides

The ready reduction of iodohydrins is utilized in the Cornforth reaction for preparing olefins from epoxides. Here the opening and reduction are carried out in one step by treatment of the epoxide, in an acetic acid-sodium acetate buffer, with sodium iodide and zinc. A less common use of iodohy-drin reduction is illustrated in the synthesis of the diene (127) ... 

The reaction can be applied to simple epoxides if polyhydrogen fluoride-pyridine is the reagent. The epoxide-to-fluorohydrin conversion has also been carried out with Sip4 and a tertiary amine.Chloro-, bromo-, and iodohydrins can also be... 

This reaction also converts 1,2-epoxides into secondary alcohols, possibly via an iodohydrin.2 Examples ... 

An interesting example exists of variation of diastereoselectivity, due both to the nature and sense of chirality of the electrophile, and to the configuration of the 2-pyrrolidinemethanol auxiliary6. Thus, the use of epoxide 16 as electrophile leads to an unexpected reversal of the diastereoselectivity relative to that observed when the corresponding O-protected iodohydrin 10 is employed. Both of the electrophiles are chiral and therefore reaction of each with the enantiomers of 1-(l-oxopropyl)-2-pyrrolidinemethanol leads to different diastereoselectivities due to the fact that there is a matched and a mismatched pair of reactions. 

Deoxygenation of epoxidesEpoxides are converted to alkenes with retention of configuration by treatment with this combination in hexane at 0 -> 25°. The reaction involves anti-opening of the epoxide to an iodohydrin, which undergoes trans-elimination to an alkcnc. 

When the phenyl substituent is one carbon removed from the epoxide ring, as in 2,3-opcxy-l-phenylpropaue, nucloophiiic attack can evidently occur at either possible reaction sites, since a mixture of iodohydrins (Eq. 714) la obtained on treatment with hydrogen iodide.1 7... 

The industrial production of Crixivan (9 H2S04) took advantage of the chirality of (IS,2R)-aminoindanol to set the two central chiral centers of 9 by an efficient diastereoselective alkylation-epoxidation sequence.17 The lithium enolate of 12 reacted with allyl bromide to give 13 in 94% yield and 96 4 diastereoselective ratio. Treatment of a mixture of olefin 13 and V-chlorosuccinimide in isopropyl acetate-aqueous sodium carbonate with an aqueous solution of sodium iodide led to the desired iodohydrin in 92% yield and 97 3 diastereoselectivity. The resulting compound was converted to the epoxide 14 in quantitative yield. Epoxide opening with piperazine 15 in refluxing methanol followed by Boc-removal gave 16 in 94% yield. Finally, treatment of piperazine derivative 16 with 3-picolyl chloride in sulfuric acid afforded Indinavir sulfate in 75% yield from epoxide 14 and 56% yield for the overall process (Scheme 24.1).17-22... 

Treatment of epoxide (34) with Bu3SnH/AIBN in the presence of Mgl2 first forms iodohydrin synthon, which rapidly reacts with Bu3Sn to form a cyclohexanol derivative (35) via 6-exo-trig ring closure of (3-hydroxyl radical as shown in eq. 3.12 [50-54]. Since the epoxides can be obtained from alkenes with peroxides, this is an indirect radical cyclization method of alkenes. 

Deoxygenation of epoxides. The reagent effects deoxygenation of epoxides via an intermediate iodohydrin (11,30), which can be isolated as the trans-isomer in some cases. This reagent can effect selective reactions in the case of some diepoxides. 

Epoxides do not, normally, react with dibromine or diiodine unless a reducing agent is present. This has been demonstrated in formation of bromo- and iodohydrine from oxiranes in presence of sodium thiosulfate1103. 

The same paper reports selective epoxidation of the 5,6-double bond of 1 by conversion to an unstable iodo-S -lactone followed by hydrolysis and treatment with base to convert the intermediate iodohydrin into an epoxide. 

Epoxides may be prepared from alkenes by the action of a peroxy acid such as m-chloroperbenzoic acid (Scheme 2.20a) or via the formation of a bromohydrin or iodohydrin and the treatment of this with base (Scheme 2.20b). Since the initial electrophile, the bromine or the iodine, is displaced in the second step when the epoxide is formed, the stereochemistry of this epoxidation is likely to differ from that of the reaction with peroxy acid. 

Organophosphorus reagents based on triphenylphosphine, or trimethylsilyl iodide, may be used to deoxygenate epoxides to re-form the parent alkene. Reactions based on this, or on a related scheme using the reduction of an iodohydrin, have been used in the synthesis and protection of alkenes as their epoxides (Scheme 2.23). 

Deoxygenation via iodohydrin intermediates using chlorosilane/sodium iodideand p-toluenesul-fonic acid/sodium iodidehas also been reported. In a natural product synthesis, an epoxide has been deoxygenated with a large excess of triethylsilane at 300 C for 30 h (equation 51). 

NaBr/H20, LiBr on Amberlyst-15 resin, TiCU-LiCl, " SiCL, I2 with a Sml2 catalyst, and Lil on silica gel. Epoxides can be converted directly to 1,2-dichloro compounds by treatment with SOCI2 and pyridine, or with Ph3P and CCl4. These are two-step reactions a halohydrin is formed first and is then converted by the reagents to the dihalide (10-48). As expected, inversion is found at both carbons. Meso epoxides were cleaved enantioselectively with the chiral B-halodiisopinocampheylboranes (see 15-16), where the halogen was Cl, Br, or I. ° Diatomic iodine gives an iodohydrin with a 2,6-bis[2-(o-aminophenoxy) methyl]-4-bromo-l-methoxybenzene catalyst. ... 

Utilization of dibromomethane also results in the isolation of iodohydrins. Based on this observation and the fact that Smia will cleave epoxides to generate iodohydrins, it has been suggested that the iodo-methylsamarium alkoxide species that is initially generated cyclizes to an epoxide intermediate. The... 

Activation of dibromo- and diiodo-methanes can also be effected using samarium powder, which generates Smh in situ. This procedure allows the isolation of the formal adduct of iodomethane to ketones and aldehydes at room temperature with very short reaction times.The iodohydrin so isolated can, of course, be readily converted to the corresponding epoxide. The reaction is thought to occur by a radical chain process. The stereoselectivity of the reaction was briefly investigated (equations 27 and 28). 

The release of ring strain in epoxides is probably responsible for the high reactivity of these special ethers. HI opens epoxides under mild conditions stereospecifically to iodohydrins (Scheme 26). The mechanism is similar to the reaction of bromide with epoxides (see Section 1.7.3.3). It should be noted, however, that reduction of epoxides to alkenes may occur if vicinal diiodides are intermediately formed, which can lose I2 under the reaction conditions. With the combination of acyl chloride and Nal unstable diiodides are avoided and 2-iodoethyl esters are formed from oxiranes (Scheme 27). ° ... 

During the enantioselective total synthesis of (-)-coriolin, I. Kuwajima and co-workers used a Darzens-type reaction to construct the spiro epoxide moiety on the triquinane skeleton. Interestingly, the usual Darzens condensation where the a-bromoketone was condensed with paraformaldehyde yielded a bromohydrin in which the hydroxymethyl group was introduced from the concave face of the molecule. This bromohydrin upon treatment with DBU gave the undesired stereochemistry at C3 (found in 3-ep/-coriolin). To obtain the correct stereochemistry at C3, the substituents were introduced in a reverse manner. It was also necessary to enhance the reactivity of the enolate with potassium pinacolate by generating a labile potassium enolate in the presence of NIS. The in situ formed iodohydrin, then cyclized to the spiro epoxide having the desired stereochemistry at C3. 

A one-step homologation/ring expansion has been reported,in which a ketone is treated with CH2I2 and Li metal. The epoxides that could conceivably be generated from the presumed iodohydrin salts... 

Elimination. The highly stereoselective conversion of iodohydrin esters to alkenes [erythro ( ), threo — (Z)] by the allyltrimethylsilane-TiCl mixture enables stereoretentive deoxygenation of epoxides via the iodohydrins. 

---