Au‐Catalyzed Addition of Nucleophiles to Chloroalkynes: A Regio‐ and Stereoselective Synthesis of (Z)‐Alkenyl Chlorides

Abstract

An unprecedented protocol has been developed for the regio‐ and stereoselective synthesis of (Z)‐alkenyl chlorides via the gold‐catalyzed addition of nucleophiles to chloroalkynes. In the presence of 1 mol‐% BrettPhosAuCl, a broad range of nucleophiles smoothly react with aromatic, vinylic, or aliphatic chloroalkynes to afford various functionalized (Z)‐alkenyl chlorides with high to excellent yields and extremely high stereoselectivity.

Gold‐Catalyzed Highly Chemo‐ and Regioselective C‐H Bond Functionalization of Phenols with Haloalkynes

“…This even applies to the Brettphos ligand, which in our hands provided a 1:1 mixture of diastereomers (Figure ). Thus our results do not confirm the findings reported in the recent literature…”

“…In this regard gold catalysis has proven to be a suitable tool for the design and development of new and valuable chemical transformations Chemo‐ and site‐selective catalytic transformations are an interesting topic in synthetic chemistry . Here we report the direct chemo‐ and site‐selective C‐H functionalization of unprotected phenols with haloalkynes by using the readily available cationic IPr‐gold(I) complex at room temperature …”

Metal‐Catalyzed Hydrofunctionalization Reactions of Haloalkynes

“…Very recently, highly efficient intermolecular hydroarylation reactions of chloroalkynes with electron rich arenes were described, making use of a catalytic system composed of the gold(I)-phosphine complex [AuCl(tBuBrettPhos)] (3) and the chloride abstractor NaBARF {sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate}. [8] Selected examples are shown in Scheme 4. The resulting (Z)-styryl chloride products were obtained in a complete regio-and stereoselective manner, as the result of the anti addition of the C-H bond of the arenes to the C≡C bond of the alkyne, which is activated by π-coordination to the cationic gold(I) fragment [Au(tBuBrettPhos)] + .…”

“…Very recently, highly efficient intermolecular hydroarylation reactions of chloroalkynes with electron rich arenes were described, making use of a catalytic system composed of the gold(I)‐phosphine complex [AuCl( t BuBrettPhos)] ( 3 ) and the chloride abstractor NaBARF {sodium tetrakis[3,5‐bis(trifluoromethyl)phenyl]borate} . Selected examples are shown in Scheme .…”

Au‐Catalyzed Stereoselective Ritter Reaction of Haloalkynes with Nitriles for (Z)‐β‐Halogenated Enamides

“…The classical Ritter reaction employs alcohols and alkenes as starting materials . Recent years, carboxylic acids were also applied in the Ritter reaction, which was first described by Minakata et al Although Ritter reaction has versatile applications in organic chemistry, there are no examples describing the reaction of nitriles with haloalkynes. Herein, we report an efficient and facile method for the synthesis of β ‐halogenated enamides via Au‐catalyzed stereoselective Ritter reaction of nitriles with haloalkynes.…”