Striking Alkenol Versus Allenol Reactivity: Metal‐Catalyzed Chemodifferentiating Oxycyclization of Enallenols

Abstract

An efficient chemodivergent metal-controlled methodology for the generation of different highly functionalized oxygen heterocycles from common enallenol substrates has been developed. Chemoselectivity control in the O-C functionalization of an enallenol can be achieved through the choice of catalyst: AuCl(3), PdCl(2), and [PtCl(2)(CH(2)=CH(2))](2) exclusively afford dihydrofurans through selective activation of the allenol moiety, whereas FeCl(3) solely gives tetrahydrofurans or tetrahydropyrans through selective activation of the alkenol moiety. We have also shown that a combination of metal-mediated hydroalkoxylation and allenic aminocyclization reactions can lead to a useful preparation of the tetrahydrofuro[3,2-b]piperidine core of the antimalarial alkaloid isofebrifugine. These divergent heterocyclization reactions have been developed experimentally and additionally, their mechanisms have been investigated by a theoretical study.

First-Row Late Transition Metals for Catalytic Alkene Hydrofunctionalisation: Recent Advances in C-N, C-O and C-P Bond Formation

“…In 2011, during the oxycyclisation study of β-lactam enallenols, Alcaide and Almendros have illustrated an efficient chemodivergent metal-controlled methodology [ 43 ]. The cyclisation of enallenols catalysed by FeCl 3 is in favour of the alkenol activation whereas the chemoselectivity with precious metal salts—[PtCl 2 (CH 2 = CH 2 )] 2 and AuCl 3 —affords the allene cycloisomerisation adduct.…”

Catalytic Selective Synthesis

“…[191] Lastly Alcaide and Almendros reported completely chemoselective Au-and Fe-catalyzed cycloetherifications of alkenes or allenes in the presence of one another (Scheme 49 d). [192] Divergent reactivity from ligand-controlled processes in Scheme 49 a and b belong to Class A, while the selectivity in the last two examples originate from distinct intermediates (Class B).…”

Silver and platinum-catalysed addition of O–H and N–H bonds to allenes

“…The advantage of platinum is that only small catalytic amounts are needed, and no stoichiometric quantities have to be employed even in the more challenging cases. Different ring-sizes can be obtained et al, 49,64 where the reaction proceeds even with β-lactam based enallenols, possessing an extra double bond in the molecule. They found high chemo-differentiation depending on the metal used, and while platinum and gold tend to activate the allene, when FeCl 3 was used, activation of the double bond was 25 observed (Scheme 57a).…”