Indolines 3.4- disubstituted

Bailey s group has elaborated a fourfold anionic domino approach leading to a N-allyl-3,4-disubstituted indoline 2-582 from 2-580 (Scheme 2.131) [300]. The central step is the formation of an aryne by treatment of 2-fluoro-N,N-diallylaniline (2-580) with nBuLi followed by a regioselechve intermolecular addition of nBuLi to give 2-581. This then cyclizes to afford a new lithiated species which is intercepted by added TMSCI. 

Witulski introduced a novel protocol for crossed alkyne cyclotrimerizations of systems such as 87 mediated by Grubb s catalyst to produce 4,6-disubstituted indolines 88 <00CC1965>. Interestingly, use of Wilkinson s catalyst [RhCl(PPhj)3] allows for the regioselective synthesis of the corresponding 4,5-substituted isomers. 

A one-pot synthesis of 3,3-disubstituted indolines was achieved by taking advantage of a sequential carbopalladation of allene, nucleophile attack, intramolecular insertion of an olefm and termination with NaBPh4 (Scheme 16.6) [10]. First, a Pd(0) species reacts with iodothiophene selectively to afford ArPdl, probably because the oxidative addition step is facilitated by coordination with the adjacent sulfur atom. Second, the ArPdl adds to allene, giving a Jt-allylpalladium complex, which is captured by a 2-iodoaniline derivative to afford an isolable allylic compound. Under more severe conditions, the oxidative addition of iodide to Pd(0) followed by the insertion of an internal olefm takes place to give an alkylpalladium complex, which is transmetallated with NaBPh4 to release the product. 

Surprisingly high ee values have been independently recorded by Bailey and Mealy and Sanz Gil and Groth for the cyclocarboUthiation of 2-lithio-Af-(2-alkenyl)anilines in the presence of (—)-sparteine (11) to form 1,3-disubstituted indolines... 

There has been a review of didehydropyridines, focusing on then formation from halopyridines and base.123 The reactions of tri-p-tolyloxonium salts with hydroxide in water yield a mixture of p- and m-cresols via a benzyne intermediate,124 as shown in Scheme 7. A benzyne intermediate, generated by loss of lithium fluoride, is also implicated in the reaction of organolithium reagents with fluoro-AyV-diallylanilincs leading to 3,4-disubstituted indolines.125 The reaction of benzyne with 1,8-diethynylnaphthalene has been shown to yield benzo [a]pyrene.126... 

The same group developed an interesting intermolecular palladium-catalyzed alienation of aryliodide with N-tosyl o-iodoanilines with nucleophiles in combination with two palladium-coupling reactions [69]. In this reaction, the N-allyl(2-iodopalladium)aniline intermediate 52 underwent an intramolecular Heck reaction followed by a cross-coupling reaction with phenyl boronic acid to give the 3,3-disubstituted indoline 53 in 78% yield (Scheme 8.27). 

Indolines and indoles were prepared by a direct electrochemical reduction of arenediazonium salts. As a result, radical intermediates were generated from which 3,4-disubstituted tetrahydrofuran skeleta were constructed <02OL2735>. A short and stereoselective total synthesis of furano lignans was realized by radical cyclization of epoxides using a transition-metal radical source <02JOC3242>. Other preparations of tetrahydrofurans using radical cyclization include the synthesis of novel amino acids L-bis-... 

M. A. Halberstam and M. B. Gordin, Kinetics of reversible photochromic reactions in the series of 1,5-disubstituted 3,3-dimethyl-6 -nitro-8 -bromospiro-[(2 /7,l -benzopyran)-2,2 -indolines], Photo-... 

In this context, it has been observed that dilithio derivative 333 cyclizes in the presence of TMEDA to give a dilithiated indoline that may be differentially functionalized by sequential addition of electrophiles, affording 1,3-disubstituted indolines 334 (Scheme 86)147. This cyclization reaction also proceeds in an enantioselective way when it is carried out in the presence of the pseudoephedrine ligand 332a. However, (—)-sparteine is in this case not able to promote the carbolithiation step, showing that the substrate structure may have a pronounced effect on the ability of a given ligand to facilitate the cyclization reaction. 

A new palladium-catalyzed enantioselective C(3)-allylation of 3-substituted 1/7-indoles 520 using trialkylboranes leads to the corresponding 3,3-disubstituted indolenines 522 (Equation 125) and indolines <2006JA6314>. The anthracene derived ligand 521 gave the best enantioselectivities. 

J-Oisubstitated SH-indoks. 3,3-Disubstituted 311-indoles (3) can be prepared readily by lithium aluminum hydride [or sodium bis-(2-mcthoxyethoxy)aluminum hydride, 3, 260-261 this volume] reduction of 3,3-disubstituted oxindoles (1), followed by oxidation of the indoline (2) with activated manganese dioxide or potassium permanganate in acetone. 

Fortunately, this Ru catalyst was also effective for 3 substituted N Boc indoles, and the 3 methyl and 3 phenyl indoles 28a and 28b were hydrogenated to the correspond ing indolines with 87 and 94% ee, respectively [39]. This catalyst system was also extended to hydrogenation of 2,3 disubstituted indoles, and only the cis 2,3 dimethy lindoline ( ) 31 was observed with 59% yield and 72% ee (Scheme 10.29). 

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