The synthesis of nitrogen-containing heterocycles, including natural alkaloids and other compounds presenting different types of biological activities have proved to be successful employing chiral sulfinyl imines derived from tert-butanesulfinamide. These imines are versatile chiral auxiliaries and have been extensively used as eletrophiles in a wide range of reactions. The electron-withdrawing sulfinyl group facilitates the nucleophilic addition of organometallic compounds to the iminic carbon with high diastereoisomeric excess and the free amines obtained after an easy removal of the tert-butanesulfinyl group can be transformed into enantioenriched nitrogen-containing heterocycles. The goal of this review is to the highlight enantioselective syntheses of heterocycles involving the use of chiral N-tert-butanesulfinyl imines as reaction intermediates, including the synthesis of several natural products. The synthesis of nitrogen-containing heterocycles in which the nitrogen atom is not provided by the chiral imine will not be considered in this review. The sections are organized according to the size of the heterocycles. The present work will comprehensively cover the most pertinent contributions to this research area from 2012 to 2020. We regret in advance that some contributions are excluded in order to maintain a concise format.
The addition of 2-bromobenzylmagnesium bromide to chiral N-tert-butanesulfinyl imines derived from tetralone type ketones proceeds with high levels of diastereocontrol. The resulting sulfinamide derivatives were transformed into dibenzoazaspiro compounds after a palladium catalyzed intramolecular N-arylation. DFT calculations have been performed to rationalize the stereochemical course of the reaction. Similar results have been obtained considering either diethyl ether or toluene as a solvent, in both cases in an excellent agreement with experimental findings. NCI topological calculations have also been used to evidence crucial noncovalent interactions. In addition, the azaspiro compounds reduced the viability chronic myeloid leukemia cells in the micromolar range. Notably, both the halogen-substituted (R)-and (S)-8g and 8h as well as (R)-8j were at least two times more effective on a multidrug-resistant derivative than on the parental cell line, exerting a collateral sensitivity effect.
11a-N-Arylsulfonyl-5-carbapterocarpans (tetrahydro-5H-benzo[a]carbazoles) were synthesized by palladium-catalyzed azaarylation of dihydronaphthalenes with o-iodo-N-(arylsulfonyl)anilines in poly(ethylene glycol) (PEG-400). Better chemical yields (moderate to good) and shorter reaction times (a few minutes at 130-170 °C) were observed in PEG-400 compared with the corresponding reactions in acetone.Crotonates undergo tandem Heck lactamizations with arylpalladium species bearing an amine group or an N-protected derivative at the ortho-position to give six-membered heterocycles such as quinolones 1a or naphthyridinones. 1b In contrast, indolines are obtained by azaarylation reactions when cyclohexadiene, 2a acyclic dienes, 2a indene, 2b norbornadiene, 2c dihydronaphthalene, 2b,c allenes, 2d or [60]fullerene 2e are used as olefins. A stereoselective arylpalladium-catalyzed cyclopentannulation of diazabicyclic alkenes with ortho-functionalized aryl halides under microwave irradiation has also been reported. 2f As part of a program to identify new compounds with antineoplastic properties based on a modification of the chemical structures of isoflavonoids, we previously synthesized LQB-226, a 11a-N-tosylpterocarpan and its 5-carba analogue LQB-223 (3a) by azaarylation of chromene or dihydronaphthalene, respectively, with N-(2-iodophenyl)-4-toluenesulfonamide (Figure 1). 3a
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