A Simple Procedure for the Synthesis of β-Hydroxyallenamides via Homoallenylation of Aldehydes

Abstract

A simple one-pot synthesis of β-hydroxyallenamides is reported. This procedure entails chemo- and regioselective hydroboration of 3-en-1-ynyl-sulfonylamides with Cy₂BH followed by homoallenylation of aldehydes to yield β-hydroxyallenamides (up to 94% yield and >20:1 dr). Controlled synthesis of up to three continuous stereochemical elements was realized. Density functional theory (DFT) calculations suggest a concerted Zimmerman-Traxler chair-like transition state. Initial results suggest that enantio- and diastereoselective synthesis of β-hydroxyallenamides with optically active hydroboration reagents is viable.

Keywords: Allenamide; Enynamide; Homoallenylation; Hydroboration; Zimmerman-Traxler Transition State.

Figure 1

Relative free energy barriers (∆G in kcal/mol) computed at the M06-2X/6-31G(d) in THF (CPCM solvation model).

Figure 2

Lowest energy TS leading to the observed diastereomers with alkyl-derived aldehydes computed using M06-2X/6-31G(d) in THF (CPCM solvation model). Selected distances are in Ångstroms.

Scheme 1

Homoallenylation prior art and proposed work.

Scheme 2

Chemo- and regioselective hydroboration of 1a with Cy₂BH

Scheme 3

Homoallenylation for three continuous stereocenters.