Reductive opening

Action of catalytic amounts of vanadium compounds on oxaziridine (52) yields caprolactam almost quantitatively. Reductive opening of the oxaziridine ring and /3-scission yield radical (118), which recyclizes with elimination of the metal ion to form the lactam (63) (77JPR274). 

A facile method for the stereospecific labeling of carbon atoms adjacent to an oxygenated position is the reductive opening of oxides. The stereospecificity of this reaction is due to virtually exclusive diaxial opening of steroidal oxides when treated with lithium aluminum hydride or deuteride. The resulting /ra/w-diaxial labeled alcohols are of high stereochemical and isotopic purity, with the latter property depending almost solely on the quality of the metal deuteride used. (For the preparation of m-labeled alcohols, see section V-D.)... 

Reductive opening of the cyclopropyl ring in 9j5,19-cycloandrostan-ll-one (234) has been achieved by treatment with a large excess of sodium in iso-propanol-OD. Analysis of the product for isotopic purity after oxidation to the corresponding ketone and base-catalyzed back exchange of the 9a-deuterium [(235) (236)] shows 19% do and 10% 62 isotopic impurities. The 10% 62 product is probably due to incomplete back exchange. 

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. 

Reductive opening with zinc and isopropanol or acetic acid is possible either at the bromo ether stage or at the a,/5,-unsaturated keto... 

Again reductive opening of the lactone ring can be achieved at the chloro lactone or a,j5-unsaturated keto lactone stages. ... 

The reaction, which is quite general for closo-carboranes, involves the reductive opening of an n-vertex c/o50-cluster followed by metal... 

The procedure is outlined in Scheme 8.33, starting from the generic allylic alcohol 125. SAE on 125 would provide epoxide 126, which could easily be transformed into the unsaturated epoxy ester 127 by oxidation/Horner-Emmonds olefmation (two-carbon extension). This operation makes the oxirane carbon adjacent to the double bond more susceptible to nucleophilic attack by a hydride, so reductive opening (DIBAL) of 127 provides, with concomitant ester reduction, diol 128. Pro-... 

The widespread occurrence and biological significance of polyoxygenated carbocycles provided the impetus to apply RCM to sugar-derived dienes. Carbohydrate carbocyclization based on a sequence of Vasella reductive opening of iodo-substituted methyl glycosides [25], and RCM of the dienes available from the resulting unsaturated aldehydes, were used to prepare a series of natural compounds (Schemes 5-7). 

Reductive opening of the oxirane ring of 188 with lithium aluminum hydride, and acetylation with acetic anhydride-DMAP, provided the pen-... 

Reductive opening of the oxirane ring of 193 with lithium aluminum hydride, and acetylation, provided compound 194. Epoxidation of 194 with mCPB A gave the epoxide 195. Opening of the oxirane ring with acetate ions, followed by acetylation, gave the tetraacetate 196, or, by exhaustive acetylation with acetic anhydride-DMAP, the pentaacetate 189. Compounds 196 and 189 were readily transformed into 190 by hydrolysis. " ... 

The final stages of the synthesis involved introduction of the final methyl group by Simmons-Smith cyclopropanation and reductive opening of the cyclopropane ring. 

The two major subunits were coupled by a Suzuki reaction in Step H-3. The Multistep Syntheses synthesis was then completed by reductive opening of the 1,3-dioxane ring, oxidation of the terminal alcohol to the carboxylic acid, carbamoylation, deprotection, and lactonization. 

The 8-methyl-8,14-cycloberbine 364, derived from the protoberberine 324 via the betaine 363, was reduced with sodium borohydride or lithium aluminum tri-tert-butoxyhydride to give a diastereoisomeric mixture of cis-and trans-alcohols (7.8 1 or 1 7.8, respectively) (Scheme 64).t)n exposure to formaldehyde the mixture underwent N-hydroxymethylation and subsequent intramolecular substitution on the aziridine ring to give the oxazolidine 365. Removal of the hydroxyl group in 365 was accomplished by chlorination followed by hydrogenolysis with tributyltin hydride. Reductive opening of the oxazolidine 366 with sodium cyanoborohydride afforded ( )-raddeanamine (360), which has already been converted to ochotensimine (282) by dehydration. 

Epoxides can also be reductively opened to form a radical. An example of an intramolecular cyclization of such a radical has recently been reported <06TL7755>. Treatment of 40 with Cp2TiCl generates an intermediate alkoxy radical, which then adds to the carbonyl of the formate ester. The product, 41, is formed as a 2 1 mixture of isomers at the anomeric carbon. This reaction is one of the first examples of a radical addition to an ester. The major byproduct of this reaction is the exo-methylene compound, 42, arising from a P-hydrogen elimination. 

A strategy based on the diastereoselective dipolar cycloaddition reaction of nitrile oxides and allylic alcoholates, has been applied to the synthesis of bis-(isoxazolines) that are precursors to polyketide fragments. These intermediates can be elaborated into protected polyols, for example, 439, by sequential chemos-elective reductive opening of each isoxazoline or, alternatively, by simultaneously, providing access to all stereoisomers of this carbon skeleton (479). 

The addition of nitrones (647) and (312) to 4-pentenofuranoside (648) derived from D-ribose, followed by reductive opening of the isoxazolidine ring in (649)... 

With an operating catalytic cycle for the reductive opening of epoxides at hand, we decided to investigate the preparatively more important formation of carbon—carbon bonds. Inter-molecular addition reactions to a,(3-unsaturated carbonyl compounds have been described for the stoichiometric process of Nugent and RajanBabu [5], The general concept behind the catalytic conditions is outlined in Scheme 12.16. 

Table 12.2. Reductive opening of epoxide 1 with various titanocene complexes.

Most of the reactions of interest involve the opening of the isoxazole ring. This reductive opening has been known for years and was reported in CHEC(1984) and CHEC-II(1996). Over the years, many different reagents have been used and/or developed for this ring-opening process examples of the most useful ones are collected in Table 5 and give an overview of the protocols available for N-O bond reduction. 

To confirm the trends observed with 10, we also investigated the behavior of epoxide 17 under ET conditions. Here, a tertiary radical would be formed after reductive opening that is more persistent than the secondary radical obtained from 10, as depicted in Scheme 8. The results of the opening reactions are summarized in Table 3. 

In summary, our studies have revealed that Sml2 is not a suitable reagent for the reductive opening of epoxides. The high Lewis acidity of this metal combined with the high nucleophilicity of the iodide ions leads to the for-... 

Reductive opening of a tetracarba-nido-hexaborane cluster to an arachno-dianion was described for 56g, which is accessible by thermal elimination of bis(trime-thylsilyl)ethyne from the bridged bishomoborirene 61 [82], Reaction of 56g with elemental lithium in THF gives [(Li thf)2]l,3-diboratabenzene 62, its reoxidation to 56g requires boiling 1,2-dibromoethane (Scheme 3.2-33). 

Scheme 3.2-33. 2e reductive opening of the nido-carborane 56g to the arachno-dianion 62 (R = SiMe3) and the reverse reaction by 2e oxidation. 

Reductive opening of oxiranes with sodium hydrogen telluride and sodium telluride... 

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