Lithium epoxides

I. Syntheses of natural prostaglandins - J. Fried and his associates recently described a new synthesis of prostaglandins which utilizes metal-alkyl epoxide openings for the introduction of both side chains. Using dlallyl copper lithium, epoxide 1 was converted in high yield to 2 ... 

The regioselectivity of the addition of terminal alkynes to epoxides is improved, when the reagents prepared from the lithiated alkynes and either trifluoroborane or chlorodiethyl-aluminum arc employed (M. Yamaguchi, 1983 S. Danishefsky, 1976). (Ethoxyethynyl)lithium-trifluoroborane (1 1) is a convenient reagent for converting epoxides to y-lactones (M. Naka-tsuka, 1990 see p. 327f. cf. S. Danishefsky, 1976). 

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

Epoxides are reduced to alcohols on treatment with lithium aluminum hydride Hydride is transferred to the less substituted carbon... 

Epoxidation of an alkene followed by lithium aluminum hydride reduction of the result mg epoxide gives the same alcohol that would be obtained by acid catalyzed hydration (Section 610) of the alkene... 

Ca.ta.lysts, A small amount of quinoline promotes the formation of rigid foams (qv) from diols and unsaturated dicarboxyhc acids (100). Acrolein and methacrolein 1,4-addition polymerisation is catalysed by lithium complexes of quinoline (101). Organic bases, including quinoline, promote the dehydrogenation of unbranched alkanes to unbranched alkenes using platinum on sodium mordenite (102). The peracetic acid epoxidation of a wide range of alkenes is catalysed by 8-hydroxyquinoline (103). Hydroformylation catalysts have been improved using 2-quinolone [59-31-4] (104) (see Catalysis). 

Another synthesis of the cortisol side chain from a C17-keto-steroid is shown in Figure 20. Treatment of a C3-protected steroid 3,3-ethanedyidimercapto-androst-4-ene-ll,17-dione [112743-82-5] (144) with a tnhaloacetate, 2inc, and a Lewis acid produces (145). Addition of a phenol and potassium carbonate to (145) in refluxing butanone yields the aryl vinyl ether (146). Concomitant reduction of the C20-ester and the Cll-ketone of (146) with lithium aluminum hydride forms (147). Deprotection of the C3-thioketal, followed by treatment of (148) with y /(7-chlotopetben2oic acid, produces epoxide (149). Hydrolysis of (149) under acidic conditions yields cortisol (29) (181). 

Solutions of RC triple-bond C—Ti(0-/-C2H2)2 can be prepared by treating acetylenic compounds, such as phenylacetylene, with butyl lithium and then Cl—Ti(0-/-C2H2)2. These materials can react with aldehydes and epoxides to give the expected addition products (215). 

Reactant for /-butyl phenolic resins. Magnesium oxide reacts in solution with /-butyl phenolic resin to produce an infusible resinate (Fig. 36) which provides improved heat resistance. The resinate has no melting point and decomposes above 200°C. Although oxides of calcium, lead and lithium can also be used, they are not as efficient as magnesium oxide and also tend to separate from solution. Where clear adhesive solutions are required epoxide resins, zinc-calcium resinates or zinc carbonate can be used. 

Lithium aluminum hydride (LiAlH4) is the most powerful of the hydride reagents. It reduces acid chlorides, esters, lactones, acids, anhydrides, aldehydes, ketones and epoxides to alcohols amides, nitriles, imines and oximes to amines primary and secondary alkyl halides and toluenesulfonates to... 

The course of the ring opening in epoxides derived from various exocyclic methylene compounds by treatment with lithium aluminum deuteride has been studied in the norbornane series. ... 

Some instances of incomplete debromination of 5,6-dibromo compounds may be due to the presence of 5j5,6a-isomer of wrong stereochemistry for anti-coplanar elimination. The higher temperature afforded by replacing acetone with refluxing cyclohexanone has proved advantageous in some cases. There is evidence that both the zinc and lithium aluminum hydride reductions of vicinal dihalides also proceed faster with diaxial isomers (ref. 266, cf. ref. 215, p. 136, ref. 265). The chromous reduction of vicinal dihalides appears to involve free radical intermediates produced by one electron transfer, and is not stereospecific but favors tra 5-elimination in the case of vic-di-bromides. Chromous ion complexed with ethylene diamine is more reactive than the uncomplexed ion in reduction of -substituted halides and epoxides to olefins. ... 

The azidohydrins obtained by azide ion opening of epoxides, except for those possessing a tertiary hydroxy group, can be readily converted to azido mesylates on treatment with pyridine/methanesulfonyl chloride. Reduction and subsequent aziridine formation results upon reaction with hydrazine/ Raney nickel, lithium aluminum hydride, or sodium borohydride/cobalt(II)... 

The configurations assigned to (8) and (9) were established by comparison with the products resulting from epoxidation of 3-methyl-5a-cholest-2-ene followed by reduction with lithium aluminum hydride to the alcohol (9). The usual /ra 5-diaxial epoxide opening requires that the hydroxyl group, formed by reduction, is axial as shown in (9). 

Reductive Opening of a 17a,20-Epoxide 17a,20-Oxidopregn-4-en-3-one (0.7 g) in 90 ml of dioxane (previously distilled over sodium) is added gradually to a solution of 1 g of lithium aluminum hydride in 50 ml of dry ether. 

To overcome this, the A -acetyl group is reduced with lithium aluminum hydride. The resulting basic enamine then reacts extremely rapidly and selectively with peracid. The derived epoxide is hydrolyzed very easily with alkali during the workup. 

Perfluorinated epoxides, which are generally susceptible to C-O cleavage during nucleophihc attack, are cleaved by lithium alummum hydnde Of the available examples, reduction of epoxides from two types of internal olefm to give alcohols IS shown [4S] (equations 37a and 37b)... 

Reduction of epoxide 21 with lithium aluminium hydride gave a crystalline branched-chain methyl heptoside derivative 24. The NMR spectra of compounds 21 and 24 were very similar. In the spectrum of compound 24 the disappearance of the two sharp doublets at r 6.80 and 7.45 (2 protons) and the appearance of a singlet at r 8.65 (3 protons) is consistent with the reductive cleavage of epoxide 21 to give a substance 24 with a methyl substituent. The multiplet at r 7.40-8.50 ( 5 protons ) was assigned to the four protons of the two methylene groups and the hydroxylic proton. 

Epoxides are reduced by treatment with lithium aluminum hydride to yield alcohols. Propose a mechanism for this reaction. 

Epoxides from aldehydes, 46, 44 Equatorial alcohols, preparation by use of the lithium aluminum hydride-aluminum chloride reagent, 47, 19... 

The C2-symmetric epoxide 23 (Scheme 7) reacts smoothly with carbon nucleophiles. For example, treatment of 23 with lithium dimethylcuprate proceeds with inversion of configuration, resulting in the formation of alcohol 28. An important consequence of the C2 symmetry of 23 is that the attack of the organometallic reagent upon either one of the two epoxide carbons produces the same product. After simultaneous hydrogenolysis of the two benzyl ethers in 28, protection of the 1,2-diol as an acetonide ring can be easily achieved by the use of 2,2-dimethoxypropane and camphor-sulfonic acid (CSA). It is necessary to briefly expose the crude product from the latter reaction to methanol and CSA so that the mixed acyclic ketal can be cleaved (see 29—>30). Oxidation of alcohol 30 with pyridinium chlorochromate (PCC) provides alde-... 

The existence of a metalated epoxide was first proposed by Cope and Tiffany, to explain the rearrangement of cyclooctatetraene oxide (8) to cydoocta-l,3,5-trien-7-one (11) on treatment with lithium diethylamide. They suggested that lithiated epoxide 9 rearranged to enolate 10, which gave ketone 11 on protic workup (Scheme 5.4) [4],... 

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