Direct Synthesis of Polycyclic Tropinones by a Condensation–[4+3]‐Cycloaddition Cascade Reaction

Abstract

A concise method of constructing polycyclic tropinone frameworks was developed. The single-step synthesis of polycyclic tropinone consists of an intramolecular [4+3] cycloaddition reaction of N-nosyl-pyrrole with oxyallyl cation that was generated in situ by an intermolecular condensation reaction of the nucleophilic functional groups on a tethered pyrrole with the aldehyde of 2-(silyloxy)-acrolein. This cascade reaction afforded various polycyclic tropinones including tri-, tetra-, and pentacyclic systems in high yields as single diastereomers.

HFIP in Organic Synthesis

“…An intramolecular [4 + 3] cycloaddition reaction of hydroxyl/sulfhydryl-tethered N -nosyl-pyrrole with oxyallyl cation was reported for the diastereoselective synthesis of polycyclic tropinones (Scheme ). The oxyallyl cation was generated in situ from condensation of the hydroxyl or the sulfhydryl group tethered to pyrrole with 2-(silyloxy)-acrolein. Initial optimization using Sc­(OTf) 3 as a catalyst in HFIP showed a dramatic boost in the yield compared to carrying out the reaction in MeNO 2 .…”

Pyrroles as Dienes in (4+3) Cycloadditions

“…Namba and co-workers described a clever and concise assembly of an intramolecular (4+3) cycloaddition precursor and its cycloaddition in one-pot cascade that provided a wide variety of polycyclic tropinones (Scheme 26). 71 Acidic conditions promoted both the in situ intermolecular condensation of a pyrrole derivative bearing a nucleophilic residue with a 2-siloxyacrolein, and its subsequent siloxyallylic cation formation and intramolecular (4+3) cycloaddition, to generate azatricyclic adducts.…”

Stereoselective (4 + 3) cycloadditions of allenyl ethers-furans by chiral auxiliaries inducing and evaluation of anti-breast cancer activity

“…As one of the most direct methods for the construction of seven-membered carbocycles, the (4+3) cycloaddition between oxyallyl cations and dienes had attracted extensive attentions in the scientific community ( Montana and Grima, 2001 ; Lohse and Hsung, 2011 ; Okamoto et al., 2018 ; Yin et al., 2018 ). Specifically, significant advances have been made by employing heteroatoms such as halogens, ( Harmata et al., 1991 ; Lee and Cha, 1999 ) oxygen, ( Masuya et al., 1998 ; Lee and Cha, 1999 ; Hayakawa and Shimizu, 2000 ; Saez et al., 2003 ; Sáez et al., 2005 ) sulfur, ( Harmata et al., 1991 ; Hardinger et al., 1995 ; Fuchigami et al., 2012 ) and nitrogen ( Myers and Barbay, 2001 ; Wei et al., 2003 ; He et al., 2014 ) to modify the stability and reactivity of oxyallyl species as well as to introduce an electronic bias in these intermediates that can lead to high regioselectivity and stereoselectivity.…”