Isomerization of N-Allyl Amides To Form Geometrically Defined Di-, Tri-, and Tetrasubstituted Enamides

Abstract

Enamides represent bioactive pharmacophores in various natural products, and have become increasingly common reagents for asymmetric incorporation of nitrogen functionality. Yet the synthesis of the requisite geometrically defined enamides remains problematic, especially for highly substituted and Z-enamides. Herein we wish to report a general atom economic method for the isomerization of a broad range of N-allyl amides to form Z-di-, tri-, and tetrasubstituted enamides with exceptional geometric selectivity. This report represents the first examples of a catalytic isomerization of N-allyl amides to form non-propenyl disubstituted, tri- and tetrasubstituted enamides with excellent geometric control. Applications of these geometrically defined enamides towards the synthesis of cis vicinal amino alcohols and tetrasubstituted α-borylamido complexes are discussed.

XBphos-Rh: a halogen-bond assembled supramolecular catalyst

“…These complexes were tested in the hydroboration of terminal alkynes towards vinylboronic acid derivatives, as the outcome of these reactions is heavily influenced by the electronic and steric properties of the ligand. 23 Methods for synthesizing vinylboronic acid derivatives, which are important synthetic intermediates, by an atom-economical hydroboration reaction 24 are scarce in the literature. 23 , 25 …”

Stereoselective synthesis of alkyl-, aryl-, vinyl- and alkynyl-substituted Z-enamides and enol ethers

“…The selective synthesis of Z -enamides is particularly challenging. 8 Alternatives to C–heteroatom bond formation have been developed, 9 but lack convergence, as no new carbon–carbon or carbon–heteroatom bond is formed. Functionalization of enamides and enol ethers via C–C bond formation has recently been achieved when they are used as nucleophiles in C–H functionalization or Heck reactions (B2).…”

Synthesis of γ‐Boryl‐Substituted Homoallylic Alcohols with anti Stereochemistry Based on a Double‐Bond Transposition

“…The anti selectivities greater than 95:5 were retained even in the cases of the 1,2‐di(boryl)alk‐1‐enes 1 j and 1 k having oxy substituents (entries 8 and 9). The amino‐substituted 1,2‐di(boryl)alk‐1‐ene 1 l also gave the anti ‐homoallylic amino alcohol 5 bl , which is in sharp contrast to the related double‐bond transposition using [CpRu(MeCN) 3 ]PF 6 , which furnished the corresponding syn isomer exclusively . The yield of 5 bl was estimated by 1 H NMR spectroscopy (entry 10).…”