A synthetic route to 1,4-disubstituted tetrahydro-ß-carbolines and tetrahydropyranoindoles via ring-opening/Pictet-Spengler reaction of aziridines and epoxides with indoles/aldehydes.

A simple and efficient synthetic route to various 1,4-disubstituted tetrahydro-ß-carbolines and tetrahydropyrano[3,4-b]indoles in high yields and stereoselectivity via LiClO4-catalyzed SN2-type ring opening of aziridines and epoxides with indoles followed by p-toluenesulfonic acid (PTSA) catalyzed Pictet-Spengler reaction is described.

Synthesis of Nonracemic 1,4-Benzoxazines via Ring Opening/Cyclization of Activated Aziridines with 2-Halophenols: Formal Synthesis of Levofloxacin.

Novel 3,4-dihydro-1,4-benzoxazine derivatives have been synthesized by an efficient and simple method in excellent enantio- and diastereospecificity (ee > 99%, de > 99%). The reaction proceeds via Lewis acid-catalyzed SN2-type ring opening of activated aziridines with 2-halophenols followed by Cu(I)-catalyzed intramolecular C-N cyclization in a stepwise fashion under one-pot conditions to furnish the 3,4-dihydro-1,4-benzoxazine derivatives in excellent yields (up to 95%). The strategy offers a short and efficient synthesis to ( S)-3-methyl-1,4-benzoxazine ( S)-3v, a late stage intermediate in the synthesis of levofloxacin.

Domino Ring-Opening Cyclization of Activated Aziridines with Indoles: Synthesis of Chiral Hexahydropyrroloindoles.

A highly enantioselective synthetic route to hexahydropyrrolo[2,3-b]indoles via Lewis acid-catalyzed SN2-type ring opening of activated aziridines with indoles having substitutions at 3- and other positions followed by cyclization in a domino fashion has been developed. Hexahydropyrrolo[2,3-b]indoles have been detosylated in the same pot to afford the corresponding products with free NH group in excellent yields (up to 95%) and enantioselectivity (up to >99%).

A Synthetic Route to Chiral Tetrahydropyrroloindoles via Ring Opening of Activated Aziridines with 2-Bromoindoles Followed by Copper-Catalyzed C-N Cyclization.

A new synthetic route to nonracemic tetrahydropyrrolo[2,3-b]indoles has been developed via SN2-type ring opening of enantiopure N-activated aziridines with 2-bromoindoles followed by copper-catalyzed C-N cyclization. A series of N-activated aziridines and 2-bromoindole derivatives with different substitution patterns were studied to afford the corresponding tetrahydropyrrolo[2,3-b]indoles in good yields and excellent ee (up to 99%). Highly substituted tetrahydropyrrolo[2,3-b]indole was synthesized as a single stereoisomer (de, ee >99%) from enantiopure trans-disubstituted aziridine.

Stereoselective Routes to Hexahydropyrroloindoles and Tetrahydropyrroloquinolines from Activated Aziridines and Electron Deficient 3H-Indoles.

An unprecedented and novel synthetic route to hexahydropyrrolo[2,3-b]indoles bearing cis-contiguous stereocenters with excellent stereoselectivities (ee of >99%, dr of ≤99:1) has been disclosed that proceeds through the ring opening of activated aziridines with electron deficient 4-substituted indoles followed by a novel cyclization in a domino fashion, thereby obviating the use of 3-substituted indoles as the prerequisite nucleophile. Another efficient synthetic route to tetrahydropyrrolo[4,3,2-de]quinolines in excellent yields (≤93%) and excellent enantioselectivity (ee of >99%) has been established via ring opening of activated aziridines with 4-bromo-1-methyl-1H-indole at relatively higher temperatures followed by Cu(I)-catalyzed intramolecular C-N cyclization in the same pot. The stability and the formation of products at different temperatures are explained by computational studies.

Synthetic route to chiral indolines via Cu(OAc)2-catalyzed ring-opening/C(sp2)-H activation of activated aziridines.

A simple strategy for the synthesis of highly functionalized indolines via Lewis acid catalyzed ring-opening of activated aziridines with various nucleophiles followed by Cu(OAc)2-mediated intramolecular C-H amination in one-pot has been developed with excellent enantio- and diastereospecificity (ee 99%; de >99%). The reaction proceeds via Cu(OAc)2-catalyzed SN2-type ring-opening of 2-phenyl-N-(2-pyridinesulfonyl)aziridine with alcohols and arene, followed by copper-mediated pyridine-2-sulfonamide directed intramolecular C(sp2)-H activation/cyclization in a stepwise fashion to furnish the indoline derivatives in excellent yields (up to 91%).