Indoline synthesis

JPS 62,490(1973) gives an indoline synthesis which can be carried one step further (dehydrogenation described in this chapter) to give DMT derivatives. See JOC 41,1118(1976) for indoles from betaketosulfoxides. 

Buchwald parlayed the powerful Buchwald-Hartwig aryl amination technology [439-447] into a simple and versatile indoline synthesis [448-452], For example, indole 368, which has been employed in total syntheses of the marine alkaloids makaluvamine C and damirones A and B, was readily forged via the Pd-mediated cyclization shown below [448], This intramolecular amination is applicable to the synthesis of -substituted optically active indolines [450], and o-bromobenzylic bromides can be utilized in this methodology, as illustrated for the preparation of 369 [451]. Furthermore, this Pd-catalyzed amination reaction has been applied to the synthesis of arylhydrazones, which are substrates for the Fischer indole synthesis [453,454],... 

Indoline synthesis 38,143 Indolizidine synthesis 8, 30, 182 Ingenol synthesis 14, 134 Ionic Liquid... 

Early examples of intramolecular aryl radical addition reactions to heteroatom containing multiple bonds included cyclizations on N=N and C=S moieties [52, 53]. Recently, cyclizations to imines have been used as part of a new enantio-selective approach to indolines (Scheme 8). In the first step of the sequence, the required ketimines 19 were obtained by phase-transfer catalyzed alkylation of 2-bromobenzyl bromides 20 with glycinyl imines 21 in the presence of a cincho-nidinium salt [54], Due to the favorable substitution pattern on the imine moiety of 19, the tributyltin hydride mediated radical cyclization to 22 occurred exclusively in the 5-exo mode. The indoline synthesis can therefore also be classified as a radical amination. 

Scheme 8 Indoline synthesis via aryl radical cyclization on imines [54]...

Scheme 9 Indoline synthesis as a multicomponent reaction including a radical cyclization step [58]...

Some effected the coupling of phenyl-, 2-fuiyl-. and 1-hexenylboronic acids with 4-thallated indole-3-carboxaldehyde (Pd(OAc),/DMF) to give 4-substituted 3-formylin-doles [148]. Regioselective thallation of indole-3-carboxaldehyde is achieved using thallium tris-trifluoroacetate in 77% yield. Indole 129, which is available by the Buchwald zirconium indoline synthesis, was used by Buchwald to synthesize 130 via a Suzuki protocol [149]. Boronate ester 130 is prepared by the hydroboration of3-methyl-1-butyne with catechol borane. Indole 131 had been used in earlier studies to synthesize the clavicipitic acids. 

Johnston JN, Plotkin MA, Viswanathan R, Prabhakaran EN (2001) Nonconventional carbon additions to azomethines. Aryl amination/indoline synthesis by direct aryl radical addition to azomethine nitrogtar. Org Lett 3 1009—1011... 

As described in the definition of Buchwald indoline synthesis, this reaction involves the formation of a zirconocene-stabilized benzyne complex that intramolecularly inserts to an A-allyl group to give a tricyclic indoline zirconacycle. In the presence of oxidating reagent or electrophiles, the indoline zirconacycle decomposes into indoline derivatives. ... 

Other references related to the Buchwald indoline synthesis are cited in the literature. 

Bailey and Liebeskind independently discovered the anionic cycUzation shown in Scheme 1 [1, 2] that leads to indoUnes and, by subsequent oxidation, to indoles. Both methods are virtually identical, involving bromine-lithium exchange followed by quenching of the aryllithium species with an electrophile (equations 1 and 4). The Af-allylindole can be deallylated with palladium (equation 2) [3], and the indohne is easily oxidized to the corresponding indole (equation 3). A selection of indoles prepared this way by Liebeskind and Zhang is shown (1-6) [2], The yields are overall for the two steps. These workers also employed chloranil (f-BuOMe, rt) to oxidize indohnes to indoles. An excellent review by Bailey and Mealy is available [4]. Bailey s related indoline synthesis via arynic cycUzation is presented in the later chapter on NucleophiUc CycUzation of Arynes (Chapter 65). 

As an extension to C-H arylations, Baudoin and co-workers reported the intramolecular alkenylation of unactivated C(sp )-H bonds. Inspired both by Knochel s intramolecular C(sp )-H alkenylation of activated benzylic positions [89, 90] and by Ohno s indoline synthesis [91], they developed a unique route toward hexahydroindoles (Scheme 17) [92]. This method afforded sp -rich products in... 

A simple indoline (and hence indole) synthesis features a Parham cyclization, e.g., 47—>48, and this has been extended to an enantioselective 3-substituted indoline synthesis, i.e., 49 +50. Oxidation of indolines 48 with o-chloranil affords the corresponding indoles in good yield." Related enantioselective indane construction has been described... 

Scheme 8.29 Cu(OAc)2-mediated indolines synthesis via intramoiecuiar aromatic C-H...

SCHEME 19.11. Phase transfer catalytic asymmetric indoline synthesis through 6jt-electrocychzation. 

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