Pyrrolo-dihydropteridines via a cascade reaction consisting of iminium cyclization and O-N Smiles rearrangement

The reactions of 5-pyrrolyl-pyrimidinyloxyacetaldehyde or methyl ketone with primary amines yielded hydroxymethylpyrrolopteridine derivatives via a cascade of iminium cyclization and O-N Smiles rearrangement. The present cascade exhibited a different profile compared to the previously reported ones, which consisted of N-N Smiles rearrangement. Lewis acid (TiCl₄) under carefully controlled conditions was employed to suppress the competing formation of imine dimers to give the desired heterocycles. A plausible mechanism involving the iminium cyclization and Smiles rearrangement is proposed. This methodology has been used to generate a series of 6-hydroxymethylpyrrolo[1,2-f]pteridine derivatives with potential biological activities.     

Formal synthesis of (−)-morphine from d-glucal based on the cascade Claisen rearrangement

The formal synthesis of (−)-morphine is described. The C-ring in morphine was prepared in an optically pure form from d-glucal using Ferrier’s carbocyclization reaction, and the vicinal tertiary and quaternary stereocenters in the C-ring were stereoselectively generated in a one-step reaction based on the cascade sequential Claisen rearrangement of an allylic vicinal diol derivative. After the one-step formation of the dibenzofuran structure, the intramolecular Friedel-Crafts type reaction effectively constructed the ABCE-phenanthrofuran skeleton. Introduction of a tosylamide function, followed by reductive cyclization furnished (−)-dihydroisocodeine, the known synthetic intermediate for (−)-morphine.     

Iminium ion-enamine cascade reaction enables the asymmetric total syntheses of aspidosperma alkaloids vincadifformine and ervinceine

Asymmetric total synthesis of (+)-vincadifformine and (+)-ervinceine is reported by utilizing an iminium ion triggered cascade reaction using chiral 3,3-disubstituted piperidine imine and 2,3-disubstituted indole derivatives coupling partner. In the first generation total synthesis, the pivotal imine is prepared in excellent stereoselectivity but in moderate yield involving a Birch reduction-alkylation strategy. Furthermore, to improve upon the synthesis of the decisive imine, the more practical second generation route is devised through a Johnson-Claisen rearrangement to access chiral 3,3-disubstituted piperidinone in excellent yield and stereoselectivity. Apart from synthesizing (+)-vincadifformine, this strategy is also exploited for the first asymmetric total synthesis of (+)-ervinceine employing an iminium ion mediated cascade reaction. This distinctive strategy simultaneously sets up two new rings, two new stereogenic centers, and three new sigma bonds in a single operation.     

Double ring-closing metathesis reaction of nitrogen-containing tetraenes: efficient construction of bicyclic alkaloid skeletons and synthetic application to four stereoisomers of lupinine and their derivatives

The double ring-closing metathesis reaction of nitrogen-containing tetraenes was studied. The selectivity of the fused/dumbbell-type products can be controlled by the electronic/steric effects of the substituents attached to the C[double bond]C bonds and the s-cis/s-trans conformational ratios of the substrates. This methodology has also been successfully applied to the enantioselective synthesis of four stereoisomers of lupinine and their derivatives.     

SnCl4-promoted rearrangement of 2,3-epoxy alcohol derivatives: stereochemical control of the reaction

The SnCl₄-promoted rearrangement of 2,2,3,3-tetrasubstituted-2,3-epoxy-1-alcohol derivatives proceeded in a regio- and stereo-controlled manner to selectively give two types of rearranged products from a single isomer by changing the protecting group of the alcohol.     

A novel reaction cascade leading to a spontaneous intramolecular dipolar cycloaddition through simultaneous generation of 1,3-dipole and dipolarophile

Ornithine methyl ester reacts with aromatic aldehydes to generate bis-Schiff bases, which depending on the structure of the aromatic aldehyde, further undergo an intramolecular cycloaddition through the transient formation of a reactive 1,3-dipole.     

Iron-catalyzed cascade reaction of ynone with o-aminoaryl compounds: a Michael addition-cyclization approach to 3-carbonyl quinolines

An efficient iron-catalyzed cascade Michael addition-cyclization of o-aminoaryl compounds including o-aminoaryl aldehydes, o-aminoaryl ketones, and o-aminobenzyl alcohols with ynones for the synthesis of 3-carbonyl quinolines is reported. The reactions proceed to afford 3-carbonyl quinoline derivatives with or without substituent at the C-4 position in good to high yields using Iron(III) chloride hexahydrate as the catalyst in the air.     

Illustrating the power of singlet oxygen chemistry in a synthetic context: biomimetic syntheses of litseaverticillols A-G, I and J and the structural reassignment of litseaverticillol E

Biomimetic syntheses of the litseaverticillols A-G, I and J are reported herein. The syntheses rely heavily on the application of two different modes of reaction for photochemically generated singlet oxygen, namely, the [4+2] cycloaddition of singlet oxygen (1O2) with furans and the ene reaction of 1O2 with double bonds. The highlight of these syntheses is a one-pot cascade sequence, involving five synthetic operations initiated by a [4+2] reaction, to form the fully functionalised litseaverticillol core. A series of regioselective ene reactions are then used to appositely functionalise the side chains. The synthesis of litseaverticillol E (both its originally proposed and its actual structures) allows a structural reassignment of this natural product.