Reductive a-allylation, of indoles

In this presentation, reductive a-allylation of indoles and reductive diallylation of lactams with allylic boranes as well as a new way to isoquinuclidine structures are described. 

Data obtained allow us to propose the following mechanism of the reductive a-allylation of indoles by allylboranes ... 

These results show unambiguously, that reductive a-allylboration of indoles proceeds with allylic rearrangement. From the reaction of 1-deuteroindole and AII3B (1 1, ether, 36°C, 7 hs), a 1 1 mixture of cis- and fro/w-2-allylindoline (78%) was isolated. 

A multi-stage synthesis of azocino[4,5,6-cd]indoles has been suggested (03M13519). From 4-bromoindole (84) with the help of successive transformations (among them the Vilsmeier-Haack reaction, Henry nitroaldole condensation, lithium aluminum hydride reduction and insertion of an allyl fragment), indole 85 has been produced in 18% yield. The cyclization of the latter on palladium... 

Friedel-Crafts alkylations of arenes with mesylates, benzyl or allyl alcohols, aldehyde/diol combinations (reductive alkylation), 1,3-dienes, or alkenes in an ionic liquid are also effectively catalyzed by Sc(OTf)3. Sc(OTf)3 works as an efficient catalyst for the condensation reaction of trimethylhydroquinone with isophytol to afford a-tocopherol. 2-Aminoalkylation of phenols with a-iminoacetates (or glyoxylate/amine) is catalyzed by Sc(OTf)3 to produce amino acid derivatives. The Sc(OTf)3-catalyzed alkylations of indoles with a-hydroxy esters, aziri-dines, acetals, and aldehydes have been utilized as key steps of total syntheses as exemplified in eq 15. ... 

Ojima and colleagues found that enamine (imine) 9 from aldehyde 8 readily cycUzed to indoles 10 upon treatment with LDA (equation 5) [5, 6]. The A-allyl group in 10 was removed by rhodium trichloride isomerization followed by acidic hydrolysis of the A-enamine (97% yield). Along similar lines. Filler s team reported an improved synthesis of 4,5,6,7-tetrafluoroindole 13 (equation 6) [7] over the method they had reported earlier. The improvements are in the reduction of nitrile 11 to phenethylamine 12 and the final oxidation to 4,5,6,7-tetrafluoromdole (13). 

Based on the early studies of radical generation from organotin hydrides and their addition to multiple bonds [1-3], particnlarly in cyclization [4-7], several groups applied this chemistry to the synthesis of indoles and indolines. For example, in 1975 Beckwith and colleagues found that < -(A -allyl-Af-methylamino)iodobenzene was converted to 1,3-dimethylindoline (78% yield) upon treatment with tri-n-butylstannane (prepared by the reduction of tri-n-butyltin chloride with LiAlH ) in the presence of AIBN (azobisisobutyronitrile) and benzene at 130°C in a sealed tube [4],... 

Ring closure reactions taking place by intramolecular addition of an aromatic radical to a double bond have been widely studied on both their regio- and stereochemical aspects [93]. Aryl halides and diazonium salts substituted at ortho- position with a 0-allyl or TV-allyl chain were used for the preparation of 2,3-dihydrobenzofuranes and 2,3-dihydro-1/7-indoles under different reaction conditions. The reaction pattern involves the generation of an aryl radical 20, which reacts with the double bond in a 5-exo trig fashion to afford the exocyclic radical 21, plausible of reduction by a hydrogen donor to obtain the reduced-cyclized product 22 (Sch. 23) [93d,94]. 

These data indicate a close relationship with ajmalicine, which is supported by chemical evidence. Thus, selenium dehydrogenation gives alstyrine lithium aluminum hydride reduction gives a primary alcohol, akuammigol (I), which possesses a typical indole UV-spectrum, with a deep minimum at 250 m/r. The formulation of this product as an allylic alcohol, stereoisomeric with tetrahydroalstonol, is further shown by its... 

Special preparations. a-Trialkylsiloxy aldehydes and l-tosyloxy-2-alkanols have been synthesized using DIBALH reduction of cyanohydrin silyl ethers and epoxy tosylates, respectively. Indoles and (Z)-allylic alcohols are acquired after simple manipulations of the primary reduction products of nitriles and a-hydroxy esters, respectively. 

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