Epoxides dissolving-metal reduction

Reactions of carbon-carbon % bonds dissolving metal reductions, conversions to alcohols and enantiomerically pure alcohols, chemo- and enantioselective epoxidations, procedures for cleavage of carbon-carbon double bonds, and reactions of carbon-carbon triple bonds... 

One of die most popular reactions in organic chemistry is dissolving metal reductions [1-3], Two systems are frequently used - sodium dissolved in ammonia with alcohol and lithium dissolved in alkylamines [4]. Although calcium is seldom used, it has been successfully applied to the reduction of a variety of compounds and functional groups [5], including aromatic hydrocarbons, carbon-carbon double and triple bonds, benzyl ethers, allyl ethers, epoxides, esters, aliphatic nitriles, dithianes, als well as thiophenyl and sulfonyl groups. 

Baeyer-Villiger oxidation (p. 853) catalytic hydrogenation (p. 844) chemoselective reaction (p. 848) dissolving-metal reduction (p. 846) enantioselective reaction (p. 857) epoxidation (p. 855) functional group interconversion (p. glycol (p. 858)... 

The alkyne was then reduced to an E alkene by a dissolving metal reduction, a step which also hydrolysed the five-membered heterocycle. The next step, an epoxidation, is needed to install the third of the chiral centres at the left-hand end of penarisidlne. However, hydrogen-bond directed epoxidation of this allylic alcohol would be expected to give the syn product shown, which has the wrong relative stereochemistry between the brown OH group and the epoxide. 

Anti additions to alkenes typically result in a stepwise mechanism formation of a cationic cyclic intermediate such as a bromonium ion, followed by backside attack by a nucleophile to open up the ring. Such is the mechanism for the anti addition of Br2. The bromination reaction results in trans bromines since the second bromine (as Br ) has to come in from the opposite face as the first bromine (as Br+) in order to do an Sn2 attack on the bromonium ion. Other mechanisms involving the bromonium ion include reaction of an aikene with Br2/H20 (adds -Br and -OH anti) and Br2/ROH (adds -Br and -OR flnfi)-Treatment of an aikene with a peroxyacid in water forms an epoxide that undergoes a ring opening in situ to give a trans diol product. Trans stereoselectivity is also seen in the dissolving metal reduction of alkynes. 

Facile cycloalkenylations of carbonyl groups have been carried out with cyclopropylphosphonium fluoroborates . Complex carbocyclic systems, such as the sesquiterpene a-cedrene, can be effectively constructed by cationic cyclization Epoxide cleavage which follows upon dissolving metal reduction of proximal cyclopropane rings makes possible the ready synthesis of functionalized strained ring compounds inaccessible by other methods... 

The metal-NHs reductions of carbonyl groups are exceedingly fast reactions for the reaction of acetone with an ammoniated electron the rate is 9 x 10 M" s". Although many, particularly older, published experimental procedures for the metal-NHs reduction of ketones employ prolonged reaction times with excess metal, these conditions are unnecessarily harsh. The reactions of carbonyl compounds with metals in NH3 are effectively instantaneous and by using short reaction times it appears that reduction of terminal alkenes and disubstituted alkynes can be avoided.In addition to the functional groups mentioned above, alcohols, amines and ethers, other than epoxides, are usually stable to reductions of aldehydes and ketones by dissolving metals. " ... 

Although Smh is more chemoselective than traditional dissolving metal reagents, it does react with sulfoxides, epoxides, the conjugated double bonds of unsaturated ketones, aldehydes and esters, alkyl bromides, iodides and p-toluenesulfonates. It does not, however, reduce carboxylic acids, esters, phosphine oxides or alkyl chlorides. In common with most dissolving metal systems, ketones with an a-hetero substituent suffer loss of the substituent rather than reduction of the carbonyl group. ... 

Table 8 Reduction of Epoxides with a Dissolving Metal ...

The procedure developed for the decyanation of secondary nitriles has been extended to a,P-unsaturated nitriles. The reaction of a-unsubstitutcd a,p-unsaturatcd nitriles with LDA in THF/HMPA results in the abstraction of a y-hydrogen from a methylene site to afford a delocalized anion. Trapping this anion at the a-position by dimethylation ° ° followed by reduction-elimination with dissolving metals leads to tetrasubstituted alkenes (Scheme 6.56). ° Epoxidation of the... 

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