One-pot synthesis of 1-azaspiro frameworks initiated by photooxidation of simple furans

Abstract

A range of 1-azaspirocycles, spiroaminals and 1,6-diazaspirocycles has been synthesized, starting from simple and readily accessible furan precursors, using a cascade reaction sequence initiated by singlet oxygen.

Singlet oxygen-mediated transformation of furans into aromatic nitrogen-containing polycycles in water

“…31 Under aqueous conditions, we propose that the equilibria between B, C and D is sidelined by the collapse of the open chain hydroperoxy ketone C affording the unsaturated keto-aldehyde E, which would in turn be the subject of an attack by the newly introduced amine (E → F). It should be emphasized here that no reductant (such as the Me 2 S utilized in such sequences [21][22][23][24] ) shall be used as an additive, thus the new protocol will not only be undertaken in an environmentally benign solvent, but will also work in a more succinct manner and have a reduced number of additives/reagents than previous methods. A series of reorganizing equilibria could then afford cation H, deprotonation of which affords the isolable, but fairly fragile, intermediate I that had been observed in previous studies.…”

“…It shows how water is expected to participate as a reactant and why the use of water as solvent might cause a serious deviation from what had been accomplished previously. [22][23][24] Singlet oxygen, generated photochemically, typically first undergoes a [4+2]-cycloaddition with the furan substrate to give an ozonide (not shown). It is reasonable to suggest that the solvent, in this case water, might open the ozonide adduct to give a hydroxy-hydroperoxy intermediate B.…”

“…[15][16][17] Beyond its many advantages as a green reagent, singlet oxygen is an ideal player in sustainable chemistry because it is both highly selective in its reactions, which eliminates the need for protecting groups and non-strategic redox manipulations, 17 and because it readily initiates one pot reaction sequences that can accomplish dramatic increases in molecular complexity in a single operation. [18][19][20] Recently, we have explored ways to include basic nitrogen components in such sequences, [21][22][23][24] so that not only polyoxygenated, but also nitrogen-bearing, polycycles can be targeted. In a new method, 22,23 we combined the singlet oxygenphotooxidation of simple furans with the introduction into the reaction sequence of both a basic nitrogen reactant and a Pictet-Spengler cyclisation; [25][26][27] thus, affording in one operation various aromatic nitrogen containing-polycycles that are present in many natural products and other bioactive targets.…”

Organic Reactions Promoted by Metal-Free Organic Dyes Under Visible Light Irradiation

“…Rose Bengal (RB) was widely used as a visible light-activated photocatalyst [32][33][34][35][36][37][38][39][40][41][42][43][44]. Tan's group studied the photoredox catalysis using RB [32][33][34][35][36].…”

“…New method for the synthesis of Meyers's bicyclic lactams was developed by using RB photocatalysis [37][38][39]. This cascade transformation is the one-pot reaction which begins from furan substrates (Figure 10) [37].…”