α-Metalated Isocyanides Toward a Tangible Reagent Space

Abstract

α-Metalated isocyanides is a versatile compound class which can easily be employed in various transformations affording tangible libraries for screening campaigns. We report the ring-opening reactions of cyclic anhydrides and lactones with three different metalated isocyanides in order to easily obtain 4,5-disubstituted oxazoles. The latter comprise useful drug-like, synthetic intermediates with two functional groups as handles for further modifications.

Instant Macrocyclizations via Multicomponent Reactions

“…Hence, we envisioned installing an -OTs functional group on an isocyanide MCR (IMCR)-based scaffold that would serve as the hub for an intramolecular aliphatic nucleophilic substitution (S N ) (Figure A). One of the most versatile building blocks in the MCR universe is the isocyanide moiety. , Thus, driven by our ongoing interest in acidic isocyanides, we focused on the isocyano alkyl tosylates 1a – c as our key building blocks. − We have prepared them on a multigram scale from inexpensive amino-1-alcohols in two steps (Figure B) . The orthogonal nucleophilic center of choice was a hydroxyl group which can be incorporated through either the aldehyde or amine component, depending on which MCR reaction is being employed (Figure C,D).…”

Multicomponent Reaction-Based Heteroannulations: A Direct Access to Fused Tetrazolo Piperazinones and 1,4-Diazepanones

“…In 2014, the Dömling group used primary amines and cyclic ketones in a UT-4CR to give an intermediate tetrazole core, which subsequently gave the desired tetrazolo[1,5-a][1,4]benzodiazepine derivatives by an ester hydrolysis/amide-bond-formation protocol (Figure 2). 46 In continuation to our interest in bifunctional isocyanides, 47,48 we employed the ethyl isocyanoalkanoates 9a and 9b and the ethyl isocyano(het)arylcarboxylates 9c and 9d as versatile building blocks, exploiting both their -NC and -CO 2 Et functionalities (Scheme 1). Our aim was to ap-ply a UT-4CR to provide easy and direct access to fused tetrazolo-1,4-diazepinones and tetrazolopiperazinones as a screening deck for future high-throughput screening.…”

“…In continuation to our interest in bifunctional isocyanides, 47 48 we employed the ethyl isocyanoalkanoates 9a and 9b and the ethyl isocyano(het)arylcarboxylates 9c and 9d as versatile building blocks, exploiting both their -NC and -CO 2 Et functionalities (Scheme 1 ). Our aim was to apply a UT-4CR to provide easy and direct access to fused tetrazolo-1,4-diazepinones and tetrazolopiperazinones as a screening deck for future high-throughput screening.…”