Exploiting rhodium-catalysed ynamide hydroacylation as a platform for divergent heterocycle synthesis

Abstract

The first examples of ynamide hydroacylation are described. The choice of ligand system determines reaction regioselectivity, resulting in α- and β-enaminones. The latter are transformed into a variety of N-heterocycles.

Diverse saturated heterocycles from a hydroacylation/conjugate addition cascade

“…However, when o -SMe-benzaldehydes were used with these alkynes, the ensuing α,β-unsaturated enones underwent a competitive 6- endo -trig cyclisation, delivering thiochroman-4-ones. 8 a Consequently, 1,4-oxathiane 7g could not be isolated. Pleasingly, incorporating electron-withdrawing groups on the o -SMe-benzaldehydes inhibited the competing pathway, providing improved yields of the desired oxathianes 7h and 7i.…”

Catalytic intermolecular hydrofunctionalizations of ynamides

“…In 2017, Willis and co-workers established a fascinating regiodivergent syn -hydroacylation of ynamides with thioether-substituted aldehydes by rhodium catalysis (Scheme 24). 51 In the presence of the electron-rich ligand Me- N -(PCy 2 ) 2 with a small bite angle, the Rh(nbd) 2 BF 4 -catalyzed coupling provided syn -α-adducts 30 as the major products, whereas the selectivity was diverted to syn -β-adducts 29 when using bis[(2-diphenylphosphino)phenyl] ether (DPEphos) as a ligand. The mechanism includes the oxidative addition of aldehydes with the Rh( i ) catalyst, ynamide insertion into Rh–H to produce hydrometallated enamides( Int-50 or Int-51 ), and reductive elimination.…”

Ligand-Controlled Regiodivergent Hydroformylation of Ynamides: A Stereospecific and Regioselective Access to 2- and 3-Aminoacroleins

“…This activation could result in a high tendency to be directly hydrogenated to form the corresponding enamine 4 , but its strong polarization could also help to control the regioselectivity of the hydroformylation reaction. On the other hand, the electron-withdrawing group attached to the nitrogen can act as a directing group and could also favor one regioisomer over the other . All together, these parameters represent as many challenges but, being tamed, they can be regarded as an asset to regioselectively perform the hydroformylation to obtain at will an isomer or the other ( 2 or 3 ) .…”