Oxidative Aldehyde Rearrangements

The effect of substrate structure on product profile is further illustrated by the reactions of cis- and trons-stilbene oxides 79 and 83 with lithium diethylamide (Scheme 5.17) [32]. Lithiated cis-stilbene oxide 80 rearranges to enolate 81, which gives ketone 82 after protic workup, whereas with lithiated trans-stilbene oxide 84, phenyl group migration results in enolate 85 and hence aldehyde 86 on workup. Triphenylethylene oxide 87 underwent efficient isomerization to ketone 90 [32]. 

It has long been known that under the influence of mineral acid fraax-benzalacetophenono oxide (JmiM-chaloone oxide) uiidminr< rearrangement to an aldehyde.1881 To determine whether phenyl or benzoyl migration attends this isomerization, House816 subjected labeled frons-benzalacetophenone oxide to the action of boron ui-fluoride, and examined isotopic distribution in the product. Incorporation of 98% of the 14C label into the aldehyde carbon (Eq. 477) c-Jrai ly established that benzoyl migration is involved. 

Boger s synthesis commenced with the preparation of the left-hand fi agment 155. A sequence of phenol protection of 151, aldehyde oxidation, Curtius rearrangement, tosylation, nitro reduction, Boc protection, and Pb(OAc)4 mediated oxidation afforded quinodiimide 152. A key Diels-Alder reaction gave 153 in good yield. Treatment of 153 in a sequence of oxonolysis, aromatization, Boc deprotection, cyclization to the lactam, A-tosyl removal, indole reduction, and selective Boc protection afforded 154. Conversion of the lactam to the... 

The approach to haplophytine proposed by Fukuyama and Tokuyama et al. did not rely on the synthesis of aspidophytine previously reported [75]. One of the main synthetic problems was the connection of the left-hand segment to the indole moiety of aspidophytine. Retrosynthetically, Fischer indole synthesis of the fully elaborated left-hand fragment 186 and the tricychc ketone 187 gave haplophytine. 186 was generated through oxidative skeletal rearrangement from precursor 188, which was accessible from indole 189 by Friedel-Crafts alkylation. Optically active ketone 187 was assembled through a stereoselective intramolecular Mannich reaction from aldehyde 190 (Scheme 33). 

The biosynthesis of the T. proceeds according to the isoprene rule . Acyclic hydrocarbons formed in this way can be converted to a multitude of compounds by substitution, oxidation, cyclization, rearrangement, etc. reactions accordingly a large number of T. (>40000 have been described to date) occurs in nature. Included among the T. are not only the hydrocarbons but also the alcohols, ketones, aldehydes, and esters (alternative name terpenoids) derived from them. For nomenclature and technical use of T., see the individual entries and Lit.. ... 

Besides being prepared by oxidation, aldehydes and ketones can also be prepared by reactions in which the first step includes the addition of water to the triple bond of the alkyne molecule. The first intermediate, the unsaturated alcohol (enol) is unstable and undergoes isomerization to the stable ketone. This type of reaction in which one isomer is transformed to another is called rearrangement. The older name for this molecular rearrangement is taulomerism and this special case is called the keto-enol tautomerism. 

Both aldoses and ketoses are oxidized to aldonic acids by Tollens reagent (Ag", NH3, HO ), so Tollens reagent cannot be used to distinguish them. Tollens reagent only oxidizes aldehydes, but since the oxidation reaction is carried out in a basic solution, a ketose is converted into an aldose by an enediol rearrangement (Section 21.5), and the aldose is then oxidized by Tollens reagent. 

The 5-oxohexanal 27 is prepared by the following three-step procedure (1) 1,2-addition of allylmagnesium bromide to an a, / -unsaturated aldehyde to give the 3-hydroxy-1,5-diene 25, (2) oxy-Cope rearrangement of 25 to give 26, and (3) palladium catalyzed oxidation to afford 27. The method was applied to the synthesis of A -2-octalone (28), which is difficult to prepare by the Robinson annulation[25]. 

If aromatic aldehydes or ketones are used, the tertiary phosphine product sometimes rearranges to a mixed phosphine oxide. 

Sharpless and Masumune have applied the AE reaction on chiral allylic alcohols to prepare all 8 of the L-hexoses. ° AE reaction on allylic alcohol 52 provides the epoxy alcohol 53 in 92% yield and in >95% ee. Base catalyze Payne rearrangement followed by ring opening with phenyl thiolate provides diol 54. Protection of the diol is followed by oxidation of the sulfide to the sulfoxide via m-CPBA, Pummerer rearrangement to give the gm-acetoxy sulfide intermediate and finally reduction using Dibal to yield the desired aldehyde 56. Homer-Emmons olefination followed by reduction sets up the second substrate for the AE reaction. The AE reaction on optically active 57 is reagent... 

Nucleophilic substitution of the halogen atom of halogenomethylisoxazoles proceeds readily this reaction does not differ essentially from that of benzyl halides. One should note the successful hydrolysis of 4-chloromethyl- and 4-(chlorobenzyl)-isoxazoles by freshly precipitated lead oxide, a reagent seldom used in organic chemistry. Other halides, ethers, and esters of the isoxazole series have been obtained from 3- and 4-halogenomethylisoxazoles, and 3-chloro-methylisoxazole has been reported in the Arbuzov rearrangement. Panizzi has used dichloromethylisoxazole derivatives to synthesize isoxazole-3- and isoxazole-5-aldehydes/ ... 

Synthesis of the remaining half of the molecule starts with the formation of the monomethyl ether (9) from orcinol (8). The carbon atom that is to serve as the bridge is introduced as an aldehyde by formylation with zinc cyanide and hydrochloric acid (10). The phenol is then protected as the acetate. Successive oxidation and treatment with thionyl chloride affords the protected acid chloride (11). Acylation of the free phenol group in 7 by means of 11 affords the ester, 12. The ester is then rearranged by an ortho-Fries reaction (catalyzed by either titanium... 

---