Transposition of the Carbonyl Group

Carhonyl shift via ally lie sulfides.2 A method for transposition of the carbonyl group of a, /J-enones to either the a- or a - position is illustrated in equation (I) for the tosylhydrazone of 3-methyl-2-cyclohexenone. 

A recently published full account of another synthesis [69] of the same alkaloid starting from the /rans-cinnamic ester 264 represented a different approach (ACD -> ACDB) to ( )-lycorine (Scheme 42). An intramolecular Diels-Alder reaction of 264 in o-dichlorobenzene furnished the two diastereomeric lactones 265 (86%) and 266 (5%) involving the endo and exo modes of addition respectively. The transposition of the carbonyl group of 265 to 267 was achieved by reduction with lithium aluminium hydride, followed by treatment of the resulting diol with Fetizon s reagent, which selectively oxidised the less substituted alcohol to give isomeric 5-lactone 267. On exposure to iodine in alkaline medium 267 underwent iodolactonisation to afford the iodo-hydroxy y-lactone 268. The derived tetrahydropyranyl ether... 

The anodic a-acetoxylation or a-medioxylation of ketones has been shown to be a powerful tool for the 1,2-transposition of the carbonyl group. The overall process is described by equation (24). ... 

A regioselective 1,2-transposition of the carbonyl group has been performed on 3-phenyl-5-bromo-4(5//)-isoxazolone, in the presence of thiourea, leading to 3-phenyl-5(4//)-isoxazolone <2003IJB2625>. 

In order to transform (259) into amarolide (267), there were three points to be considered i) the transposition of the carbonyl group from C-3 to C-l position (259 — 264), if) the hydroxylation at C-2 and C-l 1 positions, both with the introduction of an a-equatorial hydroxyl group (264 —> 265), and Hi) the oxidation of the oxane D-ring to give the 8-lactone moiety (265 —> 267). 

A variation effects alkylation and transposition of the carbonyl group. For example, methyllithium adds to the sulfenylated ester (12) to give (13). Dehydration, isomerization, and hydrolysis leads to (16). ... 

Carbonyl transposition. The last steps in a total synthesis of dl- y-coramine (5) required a 1,2-transposition of the carbonyl group of 2. This was accomplished by bissulfenylation of the lithium enolate of 2 with phenyl ben-zenethiosulfonate (1). The carbonyl group of the product was reduced and the... 

Transposition of the Carbonyl Group.—Using the imines (1) the carbonyl group of a ketone can be transposed efficiently as shown in Scheme 11. ... 

A 1,2-carbonyl transposition sequence based on the Woodward dithioacetalisa-tion reaction was used to relocate a carbonyl group in 95.1 [Scheme 2.95] to the adjacent position in 95 6.190 A total of 6 steps were required in which the key step was the dithioacetalisation of the a-hydroxymethylene derivative 95 2. After reduction of the carbonyl group, the dithiane was hydrolysed to the a-acetoxy ketone whence dissolving metal reduction removed the acetate function. 

During the final stages of the total synthesis of (-)-subergorgic acid by L.A. Paquette and co-workers, the transposition of a tricyclic enone was needed. The enone was exposed to the Luche conditions and an 85 15 mixture of diastereomers was obtained. In order to achieve this level of diastereoselectivity, the reaction temperature had to be lowered to -50 °C instead of the usual 0 °C. The major product was formed via the exo attack of the carbonyl group by the hydride. The allylic alcohol was later converted to the corresponding sulfoxide followed by a Mislow-Evans rearrangement to the isomeric allylic alcohol. 

In 1,2-alkylative carbonyl transpositions where the carbonyl group moves forward into the newly added fragement, e. g. 63 - 64, the reagent behaves as an acyl anion equivalent. We have seen one example of this in the synthesis of the occidentalol intermediate 8. Phosphine oxides with OR or SR substituents on the a-carbon 65 are ideal reagents for this process as the Horner-Wittig reaction gives vinyl compounds which can be hydrolysed to 64. 

The reaction also has been used for transposition of a carbonyl group. Oxidation of propiophenone (4), followed by reduction with sodium borohydride and acetylation, gives the a-acetoxy acetoxime (5), which on treatment with excess chromous acetate affords phenylacetone (6). 

Transpositions of a carbonyl group. An a-sulfenylated ester (1), prepared as described above, can be reduced by lithium aluminum hydride in THF at 25° in high yield to the alcohol (2). Treatment with thionyl chloride (benzene or ether) yields the primary chloride (3), which can be dehydrohalo-... 

The transposition of a functional group, for example carbonyl, C=C or CsC, similarly may set the stage for a highly effective simplification, as the retrosynthetic conversion of 14 to IS + 16 shows. 

Allylsilanes react with carbonyl compounds to transfer the allyl group with 1,3-transposition, in the presence of Lewis acids, typically titanium(IV) chloride47. Recently this reaction has been carried out under super-acid catalysis48. Transfer of the allyl group is also induced by tetrabutylammonium fluoride, but in this case reaction takes place regioselectively at the less substituted end of the allyl fragment49. 

Umezawa and co-workers9 have reported a new synthesis of the tetracyclic lactam (19), which is a key intermediate in Torssell s synthesis of lycorine (cf. Vol. 9, p. 139) the Japanese work (Scheme 2), therefore, represents a formal synthesis of the alkaloid. The cyclohexyl isocyanate (15) (trans-diequatorial aryl and isocyanate groups) cyclized to a tricyclic lactam, which by reduction with a hydride and hydrolysis gave the ketone (18). The tetracyclic ketone (16) was converted into the 2,3-ene (17) by a Cope elimination reaction, and the synthesis of compound (19) was completed by transposition of the lactam carbonyl group from C-5 to C-7. 

The carbonyl adducts of allyl phosphine oxides, e. g., 24 and 29 can also be used to make allyl alcohols32 by the reductive removal of the Ph2PO group with lithium aluminium hydride a reaction involving transposition of the double bond, e. g., 24 36. In this approach, the allyl anion of 23 is a reagent for the vinyl anion synthon 37. 

The next phase of the synthesis involved the transposition of aldol adduct 61 to the protected "aldol" adduct 60. (3-Hydroxyketone 61 was subjected to conditions (NaBH4, AcOH) which effected a direct reduction of the carbonyl moiety of 61 and thereby introduced the axial C(9) hydroxyl functionality of 67 with complete stereocontrol through an intramolecular delivery of hydride within an alkoxide intermediate at C(7). After diprotection of both hydroxyl groups of 67, chemoselective deprotection of hydroxyl at C(7) and Swern oxidation, ketone 60 was isolated. The enolate derivative of 60 could be stereoselectively p-methoxybenzylated, and the resulting ketone was reduced to the wrong equatorial alcohol 68. The C(7) stereogenic center was inverted by treatment of the nosylate derivative of 68 with rubidium acetate to afford the desired acetate 69 accompanied by the syn elimination product (15%). 

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