Gold-catalyzed propargylic substitutions: Scope and synthetic developments

Abstract

This personal account summarizes our recent developments in gold-catalyzed direct substitutions on propargylic (allylic, benzylic) alcohols, with various nucleophiles (and bi-nucleophiles) based on the σ- and/or π-acidity of gold(III) complexes. Synthetic developments are also briefly described.

Keywords: direct substitutions; gold; isoxazolines; propargylic substitutions.

Scheme 1

Gold-catalyzed propargylic substitutions.

Scheme 2

Propargylic substitution: scope of substrates.

Scheme 3

Propargylic substitutions on allylic/propargylic substrates.

Scheme 4

Direct propargylic substitutions: Scope of nucleophiles.

Scheme 5

Meyer–Schuster rearrangements.

Scheme 6

Silyl-protected propargyl alcohols in propargylic substitutions.

Scheme 7

Acetylacetone as nucleophile in direct propargylic substitution.

Scheme 8

Enantiomerically enriched propargylic alcohols.

Scheme 9

Scope of ‘activated’ alcohols in direct substitution reactions.

Scheme 10

BF₃ vs AuCl₃ in propargylic substitutions [25].

Scheme 11

The use of bis-nucleophiles in direct propargylic substitutions.

Scheme 12

Tandem reactions from protected hydroxylamines and propargylic alcohols. P = Cbz, PhSO₂.

Scheme 13

Tentative hydrolysis of bis-adduct 24a.

Scheme 14

Iron-catalyzed propargylic substitutions.

Scheme 15

Isoxazolines formation.

Scheme 16

Addition of nucleophiles to isoxazolines.

Scheme 17

Potential mechanistic pathways.

Scheme 18

Synthesis of furans from homoproargylic alcohols.

Scheme 19

Synthesis of furans.

Scheme 20

Propargylic substitutions: Synthetic applications. GH2 = Grubbs–Hoveyda 2^nd generation catalyst.