ABSTRACT
A novel formal [2+2+2] strategy for the stereoselective elaboration of polycyclic indole alkaloids is described. Upon treatment with the catalyst InCl3 (5â mol %), tryptamine-derived enamides reacted readily with methylene malonate, thus enabling rapid and gram-scale access to versatile tetracyclic spiroindolines with excellent diastereoselectivity (21 examples, up to 95 % yield, up to d.r.>95:5). This strategy provides a concise approach to alkaloids isolated from Strychnos myrtoides, as demonstrated by a short synthesis of 11-demethoxy-16-epi-myrtoidine.
Subject(s)
Indole Alkaloids/chemical synthesis , Polycyclic Compounds/chemical synthesis , Spiro Compounds/chemical synthesis , Strychnine/analogs & derivatives , Cyclization , Indole Alkaloids/chemistry , Molecular Conformation , Polycyclic Compounds/chemistry , Spiro Compounds/chemistry , Strychnine/chemical synthesis , Strychnine/chemistryABSTRACT
A direct asymmetric dearomative amination of tryptamines with O-(2,4-dinitrophenyl)hydroxylamine (DPH) was achieved using CuBr-bisoxazoline complex as a catalyst, affording 3a-amino-pyrroloindolines in good to excellent enantioselectivity under mild reaction conditions. Furthermore, the synthetic value of this method was demonstrated in the total synthesis of (-)-psychotriasine in a highly concise manner.
Subject(s)
Copper/chemistry , Indoles/chemistry , Tryptamines/chemistry , Amination , Catalysis , StereoisomerismABSTRACT
Stereocontrol in the synthesis of structurally complex molecules, especially those with all-carbon quaternary stereocenters, remains a challenge. Here, we reported the preparation of a class of tetracyclic cyclopenta-fused spiroindoline skeletons through Cu(II)-catalyzed intramolecular [3 + 2] annulation reactions of donor-acceptor cyclopropanes with indoles. Both cis- and trans-diastereomers of tetracyclic spiroindolines are accessed with high selectivities by altering the remote ester groups of cyclopropanes. The origins of this stereocontrol are identified using DFT calculations: attractive interactions between the ester group and arene favor the generation of the trans isomer, while the formation of the cis isomer is preferred when steric repulsions become predominant.
Subject(s)
Indoles/chemical synthesis , Spiro Compounds/chemical synthesis , Catalysis , Copper/chemistry , Cyclopropanes/chemistry , Esters/chemistry , Indoles/chemistry , Spiro Compounds/chemistry , StereoisomerismABSTRACT
The first enantioselective copper catalyzed cyclopropanation of internal olefins with diazomalonates is reported. This process provides a new method for the synthesis of chiral 1,1-cyclopropane diesters. With a chiral bi-side arm bisoxazoline-copper(I) complex, the reaction performed well over a series of substrates, giving the desired products in good yields (up to 95%) and excellent enantioselectivities (90-95% ee).