Oxidative rearrangements dienolates

A simple two-step protocol for the generation of a terminal diene is to add allyl magnesium bromide to an aldehyde or a ketone and subsequent acid or base catalysed dehydration (equation 34)72. Cheng and coworkers used this sequence for the synthesis of some indole natural products (equation 35)72a. Regiospecific dienones can be prepared by 1,2-addition of vinyllithium to a,/l-unsaturated carbonyl compounds and oxidative rearrangement of the resulting dienols with pyridinium dichromate (equation 36)73. 

G. Majetich, S. Condon, K. Hull and S. Ahmad, 1,3-Oxidative Rearrangements of Dienols, Tetrahedron Lett. 30, 0000 (1989). 

Citral is prepared starting from isobutene and formaldehyde to yield the important C intermediate 3-methylbut-3-enol (29). Pd-cataly2ed isomeri2ation affords 3-methylbut-2-enol (30). The second C unit of citral is derived from oxidation of (30) to yield 3-methylbut-2-enal (31). Coupling of these two fragments produces the dienol ether (32) and this is followed by an elegant double Cope rearrangement (21) (Fig. 6). 

Diborneo-l,2-dithiin 25 was synthesized from (R)-thiocamphor 212 via disulfide oxidation (of the enethiol form) and Cope rearrangement to the bis-thiocamphor, which was deprotonated employing NaH/DMF to form the dienolate and then finally oxidized with K3[Ee(CN)6] (Scheme 58) <1995T13247, 1994TL1973> only the racemic dithiin derivative 25 was obtained. 

The plant bufadienolide scillarenin (500) has been synthesized. The starting material was 15a-hydroxycortexone (501), which was converted into the diketone ketal (502) by cupric acetate oxidation at C(21), followed by selective ketalization and tosylate elimination. Protection at C(3) as the dienol ether, oxiran formation at C(20) with dimethylsulphonium methylide, and regeneration of the C(3)- and C(21)-oxo-groups by acid hydrolysis then provided (503). Selective reaction at C(21) with the sodium salt of diethyl methoxycarbonyl-methylphosphonate, and boron trifluoride rearrangement of the epoxide ring to the aldehydo-unsaturated ester (504), was followed by enol lactonization to the bufadienolide (505). This was converted, in turn, to scillarenin (500) via the 14,15-bromohydrin, by standard reactions. Unsubstituted bufadienolides have also been prepared by the same method. 

The dienol-benzene rearrangement has been used to advantage to explain the structures of several abnormal aporphine alkaloids (49) from a biogenetic point of view, and has also allowed the first s3uithesis of the aporphine alkaloid isothebaine (L) (50). (+ )-Orientaline (XLVII) was oxidized by alkaline ferricyanide to give a mixture of two dienones (XLVIII) in 4% yield. One of the dienones was reduced with sodium borohydride to a mixture of two dienols XLIX which, without... 

Two studies have appeared dealing with the phenolic oxidative coupling of the dihydric benzylisoquinoline LI. In the first study, oxidation of LI with potassium ferricyanide yielded two dienones (LII), one of which was obtained crystalline. The crystalline material was reduced with sodium borohydride to two noncrystalline dienols (LIII) which underwent dienol-benzene rearrangement in anhydrous methan-olic hydrogen chloride to ( )-corydine (XXVI). Rearrangement of the... 

Oxidation of a number of benzylisoquinoline bases followed by the dienone-phenol or dienol-benzene (after reduction with borohydride) rearrangement has afforded several aporphine bases (27, 28, 49, 96, 229,... 

The biosynthesis of aporphine alkaloids takes the course—laudanoso-line, norlaudanosoline, reticuline, or orientaline—by means of phenolic oxidation via the cyclohexadienone proaporphine (27, 28, 39, 40, 47, 49, 65, 66, 68, 69,147,148,150, 229, 231, 240, 250, 275, 349, 445, 451, 512) after dienone-phenol or dienol-benzene rearrangement, as described in more detail in the preceding section. The foregoing results, considered as a whole (39,49), provide good evidence that isothebaine is biosynthesized in P. orientale along the following pathway ... 

The spiro-dihydrofuran (61) is converted into the cyclobutane derivative (62) under the influence of trifluoroacetic acid. The lithium dienolate (64), derived from the furanone (63), yields solely y-alkylated products on treatment with alkyl halides. Thermolysis of the t-butylperoxybutenolide (65) produces about equal amounts of the hydroxy-furanone (67) and the indenone (68), presumably via the oxide radical (66). Attack of iodide ion on the salt (69) results in the formation of methyl iodide, butanolide, and (surprisingly) methyl 4-iodobutanoate. A description of a study of the photochemical rearrangement of the tetrahydrofurans (70) to the bicyclic oxetans (71) has been presented. ... 

Overman s retrosynthetic analysis is depicted in Scheme 1. Pentacyclic ketone 4, derived from allylic alcohol 7 by an aza-Cope-Mannich rearrangement of formaldiminium ion derivative 6 furnished 3 through the C5 hemiketal disconnection. An intramolecular oxidative coupling of a dienolate generated from indole-... 

There have been two reports of using light to promote this reaction. These studies support the Cook intermediate 6 and also the oxidative byproducts previously mentioned. The reaction was proposed to initiate via a type II Norrish reaction forming 62, which rearranges into a mixture of two dienols. Dienol 64 proved analogous to the Cook intermediate and the believed productive compound to undergo Elbs cyclization to 65. Further... 

Substituted, terpenoid 3,7-dienoic acid esters, and presumably other 3,7-dienoates, can be obtained by consecutive ortho-Claisen and Cope rearrangements of 2,5-dienols (Scheme 47). In the example shown, the starting dienols were obtained from mesityl oxide. 

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