Reductive transposition derivative

Isoindolo[2,l-a]benzimidazole (163) was the sole product produced (80% yield) on irradiation of the quinoxaline derivative 162 in methanol.157 The authors propose a mechanism that involves initial ringopening of 162 to a diazocine biradical that undergoes transposition and reduction to the azapentalene 163. 

Transposition reactions of diazocinediones (Sections III,By4,a and IV,B,2) can lead to compounds that are aza or benzo derivatives of two basic systems 453 and 454.165,314,321,323 331,424 Two groups of workers323c, 323d examined the reduction of 327 with lithium aluminum hydride, and the results of the earlier, more complete study323c are shown in Scheme 21. 

See also page 47, Section 93 and page 49, Section 9.4, for reduction of sulfur-containing derivatives of alcohols and phenols and page 229, Section 4, for reduction of allylic sulfonates and sulfones with double bond transposition. 

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... 

Scheme 12.6). Stereoselective reduction and chromatographic separation afforded diastereomerically pure derivative 32 in 94% ee. Removal of the silicon protecting group, followed by acetylation of the two secondary alcohols, set the stage for an elegant palladium-catalyzed allylic transposition that provided compound 33 with...

In these compounds, there is a marked relationship between molecular geometry and biological activity. From values reported in the literature and according to our own studies, the E isomers, in which the residue originating from the aldehyde is in the transposition to the triazole, are markedly superior to the Z isomers in their biological activity. By suitable control of the reaction conditions, it is possible to achieve an almost complete isomerization to the unsaturated E-triazolylketones. Subsequent reduction leads to the more active E-alcohols. This group of N-vinylazoles includes the triazole derivative S 3308 (Sumitomo), currently under development as... 

A carbonyl transposition based on enamine hydroboration has been described by Gore and coworkers167-169. The same reaction attempted on enamines of 5a-3-keto-steroids resulted in an unusual reactivity of diborane, leading to reduction of the enamine double bond. The 3 a-derivative prevailed over the 3/2-derivative as a consequence of the presence of the 19-methyl group, as demonstrated successively for the 19-nor-steroids170 (Scheme 117). 

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. 

Reactions of Enols and Enolate Anions.—Several methods are described for transposition of an oxo-function to the adjacent site. They involve formation of a suitable a-substituted derivative (hydroxymethylene ° or benzylidene ) and subsequent steps which transform the substituent into an isolated oxo-group. Condensations leading to both the 2-hydroxymethylene- and the 2-arylidene-3-oxo-steroids are described for 3-ketones of the 5jS-series, and also of the 5j8,9j5,10a-( retro ) series.Condensations of aromatic aldehydes at C-2 in the 5 -series are unusually slow enolisation towards C-4 is preferred, but steric compression between C-4 and C-6 in 5/3-compounds severely hinders the condensation reaction at C-4, allowing reaction at C-2 via the 2-enol. Reduction of a 21-hydroxymethylene-pregnan-20-one (337) with sodium borohydride afforded the homopregnanediol (338), although reduction of enolised P-dicarbonyl compounds frequently proceeds via elimination to give enones, and thence allylic alcohols. 

The structure of the major FeCla-catalysed ene adduct of chloral to (15,55)-(-)-/3-pinene (Vol. 8, p. 54) is (209). Preferred ene reaction of PhS02NS0 with 8-pinene has been used for the almost quantitative separation of a- and /8-pinene another application of this reaction allows the conversion of a-pinene into jS-pinene via a triple allylic transposition sequence of ene-reaction, reduction, reductive silylation, and hydrolysis/ Ene reactions of jS-pinene under pressure have been observed (74—100% yields) at room temperature thus limiting, for example, retro-ene side-reactions. The full papers on a-pinene/allo-ocimene pyrolysis (c/. Vol. 7, p. 12) and on the thermal rearrangement of (208 X = H or Me) have been published (Vol. 4, pp. 61, 62) (208 X = H) is reported to yield only (210) in contrast to unpublished observations of Prater who has reported the rearrangement of (210) to (208 X = H) and the formation of p-menthadiene derivatives from (208 X = H or 0-)6 ... 

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%). 

---