Designed Bifunctional Phosphine Ligand-Enabled Gold-Catalyzed Isomerizations of Ynamides and Allenamides: Stereoselective and Regioselective Formation of 1-Amido-1,3-dienes

Abstract

By using designed biphenyl-2-ylphosphines functionalized with a remote basic groups as ligands, N-alkynyl-o-nosylamides are directly converted to (1E,3E)-1-amido-1,3-dienes with excellent diastereoselectivities under gold catalysis. With allenamides as substrates, the gold-catalyzed isomerizations are high yielding and applicable to a broad substrate scope including various nitrogen protecting groups and exhibit unprecedented (3E)-selectivities for the distal C-C double bond and good regioselectivities. Combining this gold catalysis with one-pot Diels-Alder reactions leads to rapid assembly of valuable bicyclic compounds.

Buchwald‐Type Ligands on Gold(I) Catalysis

“…In this reaction, the propargylic hydrogen is acidified upon activation of the alkyne by gold(I) and the strategically positioned weak Brønsted base functions as a proton shuttle in the isomerization process, which leads to the formation of allenyl intermediate 92 . Similarly, the isomerization of ynamides and allenamides, propargylic esters and allyl ynoates has been reported.…”

Bifunctional Ligand Enables Efficient Gold‐Catalyzed Hydroalkenylation of Propargylic Alcohol

“…They are designed to achieve beneficial interactions between such a basic group and either the substrate or incoming nucleophiles by harnessing the robust linear organization of ligating atom–gold–alkyne centroid in gold(I) complexes (Figure a). With the amine‐based ligands, including L1 – L4 , several gold catalysis reactions are enabled by interactions between the basic nitrogen atom and alkyne/allene substrates ,,. With WangPhos featuring a remote amide group as a ligand, nucleophilic additions to alkynes are accelerated owing to hydrogen bonding between the amide group and incoming nucleophiles, in the form of general‐base catalysis ,,.…”

Bifunctional Biphenyl-2-ylphosphine Ligand Enables Tandem Gold-Catalyzed Propargylation of Aldehyde and Unexpected Cycloisomerization

“…To date, this class of potentially versatile organogold species is conspicuously missing in catalysis, except our recent work where they promptly undergo protodeauration ( vide infra ). 4 Studying its completely unexplored reactivities beyond protonation 4 in catalytic settings should dramatically enrich gold catalysis and, moreover, the chemistry of σ -allenylmetals. 5…”

“…Our lab has devoted much effort lately to the development of designed biphenyl-2-ylphosphine ligands 4,6 featuring a remote basic functional group, such as an amide, 6c-f an aniline, 4a or a tertiary amine, 4b,6a,b and the application of them in the discovery of highly efficient or unprecedented gold catalysis. In our early work on soft propargylic deprotonation, 4a we proposed the isomerization of an alkyne to an allene via an in situ generated σ -allenylgold (i.e., A , Scheme 1A). DFT calcuations corrobrate such an intermediate and its subsequent protodeauration step.…”

“…This strategy enables catalytic propargylic C–H functionalization, which has been seldom documented. 4 Herein, we disclose a premilinary implementation of this design.…”