Fragmentation reactions Lead tetraacetate

Diethylamino)sulfur trifluoride, 110 Formylation (see also Carbonylation) Vilsmeier reagent, 341 Fragmentation reactions Cerium(IV) ammonium nitrate, 67 Copper(II) acetate-Iron(II) sulfate, 85 Lead tetraacetate, 155 Friedel-Crafts alkylation Aluminum chloride, 15... 

Formation and /S-fission of bicyclic tertiary alkoxyl radicals from the corresponding alcohols are well known [38] [40]. The treatment of 5a-cholestane-3/3,5-diol-3-acetate, VII/70, and the 5/3-alcohol, VII/71, respectively (Scheme VII/15), with one molar equivalent of lead tetraacetate in the presence of anhydrous calcium carbonate gives radical fragmentation reactions. The products are the two (E)- and (Z)-3/3-acetoxy-5,10-seco-l(10)-cholesten-5-ones (VII/72 + VII/73) [40]. The ratio of VII/73 VII/72 is 63 10 [41] [42] [43]. 

As an alternative to the lead tetraacetate oxidation, (diacetoxyiodo)benzene can be used to initiate a fragmentation reaction which leads to unsaturated medium-sized lactones [110]. The structures of the starting materials are similar to those of compounds VII/157, VII/160, and VII/163. The same stereochemical consequences are observed as mentioned above. 

Tetrahydrofuranes. Cekovic, BoSnjak, and Mihailovic have reviewed their work on the oxidative cyclization of aliphatic alcohols to tetrahydrofuranes by oxidation with lead tetraacetate. The reagent should be free of acetic acid. Anhydrous calcium carbonate can be added to neutralize the acetic acid in the oxidant and that formed during the reaction. The reaction involves selective oxygenation of a 8-carbon the actual mechanism is uncertain, but is probably a radical reaction. Direct oxidation of the alcohol is generally of minor importance, but P-fragmentation can be a problem, particularly when a stable benzyl or allyl radical is formed. 

Barton oxidation was the key to form the 1,2-diketone 341 in surprisingly high yield, in order to close the five-membered ring (Scheme 38). The conditions chosen for the deprotection of the aldehyde, mercuric oxide and boron trifluoride etherate, at room temperature, immediately led to aldol 342. After protection of the newly formed secondary alcohol as a benzoate, the diketone was fragmented quantitatively with excess sodium hypochlorite. Cyclization of the generated diacid 343 to the desired dilactone 344 proved very difficult. After a variety of methods failed, the use of lead tetraacetate (203), precedented by work performed within the stmcmre determination of picrotoxinin (1), was spectacularly successful (204). In 99% yield, the simultaneous formation of both lactones was achieved. EIcb reaction with an excess of tertiary amine removed the benzoate of 344 and the double bond formed was epoxidized with peracid affording p-oxirane 104 stereoselectively. Treatment of... 

Ketene Ikioacetals. The oxidation of a-hydroxy thioacetals with 1 equiv. of lead tetraacetate in some cases results in clean fragmentation to a ketene thioacetal. The reaction proceeds particularly well when the reacting center is part of a strained ring system, as in examples formulated in equations (I) and (II). The oxidation of one open-chain substrate also proceeded cleanly. In general, the reaction tends to be slow and capricious (7,186-187), but can be a useful approach to ketene acetals with an unprotected carbonyl group. 

By suitable choices of substrate such reactions have been used to introduce substituents into the C(i8) and C(i9) methyl groups, and also at various skeletal positions. The necessary free radicals have been generated by fragmentation of iV-halo-amines, azides, nitrites, hypohalites, and also of alcohols, by the action of lead tetraacetate. 

The subsequent cycMsation of the alkoxy-radical depends upon its ability to attack a suitably placed C-H bond on the -carbon atom. The alternative to cyclisation under homolytic conditions is fragmentation of the alkoxy radical into a carbonyl compound (ii) and an alkyl radical (10), which affords a mixture of stable products by further transformations. Heusler [44] reached similar conclusions from a study of steroid reactions, and has demonstrated a close similarity between thermally and photolytically-induced homolytic reactions with lead tetraacetate in hydrocarbon solvents. 

A number of skeletal fragmentation reactions resulting from treating steroid alcohols with lead tetraacetate require comment. These reactions occur as the alternative to cyclic ether... 

The tetrahydrochromane (2) is oxidized by /M-chloroperbenzoic acid to 6-ketonon-anolide (5) under carefully controlled conditions (2.8 equiv. of peracid, methylene chloride, room temperature). The reaction is postulated to involve the hydroxy peracid (4) as an intermediate which undergoes fragmentation. Use of perphthalic acid gives the glycol (3). which on cleavage with lead tetraacetate gives (5). 

In our total synthesis of discorhabdin A, the A,(9-acetal compound 96 acted as a key compound for the construction of the A,5-acetal compound (see Scheme 31), and was prepared by the oxidative fragmentation reaction of an a-amino alcohol 95 initially using the highly toxic lead tetraacetate. We then developed a new method using the low toxic hypervalent iodine(III) reagent. Thus, the reaction of the... 

Lead tetraacetate (abbreviated LTA) reacts with diols to give the same kind of oxidative cleavage. When 69 is treated with LTA, the initial cyclic product is cyclic intermediate 73, which fragments to butanal and acetaldehyde. Periodic acid gives the same cleavage reaction. Both periodic acid and lead tetraacetate are mild and effective reagents for the oxidative cleavage of diols. 

One of the best routes to arynes is the oxidation of aminotriazoles (49j) with lead tetraacetate. Variations involve generating the intermediate nitrene 57 or nitrenoid with other oxidizing agents or from other precursors (49k-49n). By analogy the nitrene 58 or nitrenoid obtained by oxidation of 1-aminoindazole (59) might be expected to fragment to arynes by loss of Nj and a nitrile. In fact this reaction constitutes an excellent synthesis of the previously discussed aryne precursors, the 1,2,3-benztriazines (49e). A vibrationally excited form of 49c is presumably an intermediate in the pyrolysis of sulfoximides of 2-aminoindazoles (60) to arynes. 

Condensation of silylimine of (5)-lactic aldehyde with lithium enolate of t-butyl isovalerate affords the -lactam in 80% chemical yield and in a 97 3 diastereomeric ratio. The mixture was desilylated and treated with lead tetracetate to give, in one step, through a radical fragmentation reaction, the 4-acetoxy derivative as a 1 1 4(R) 4(S) imeric mixture. The lack oi stereospecificity is not easy to rationalize expecially if one considers that the analogous lead tetraacetate induced oxidative decarboxylation is completely trans stereoselective. Both reactions should have the same radical intermediate. However, this lack of stereospecificity is not important for the success of the synthesis since the mixture of diastereoisomers exclusively affords the trans 4-substituted azetidinone by the subsequent Merck procedure (Scheme 9). 

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