Stereo- and Regioselective Dimerization of Alkynes to Enynes by Bimetallic Syn-Carbopalladation

Abstract

Enynes are important motifs in bioactive compounds. They can be synthesized by alkyne–alkyne couplings for which a number of mechanisms have been suggested depending on catalyst type and dominant product isomers. Regarding bimetallic pathways, hydrometalations and anti-carbopalladations have been discussed to account for the formation of geminally substituted and (Z)-configured enynes, respectively. Here we report a bimetallic alkyne–alkyne coupling that yields (E)-configured enynes. An unusual type of acetylide Pd bridging was found in putative catalytic intermediates which is arguably responsible for the regio- and stereochemical reaction outcome. Mechanistic studies suggest that a double μ–κ:η2 acetylide bridging enables a bimetallic syn-carbometalation. Interestingly, depending on the reaction conditions, it is also possible to form the geminal regioisomer as major product with the same catalyst. This regiodivergent outcome is explained by bi- versus monometallic reaction pathways.

Palladium‐Catalyzed Tail‐to‐Tail Reductive Dimerization of Terminal Alkynes to 2,3‐Dibranched Butadienes

“…Among them, the dimerization of terminal alkynes as an atom‐economic and straightforward method for synthesizing conjugated enynes, [2] dienes, [3] and diynes [4] has attracted considerable interest. The dimerization of terminal alkynes through head‐to‐tail [2d,f,g,i–k,p] and head‐to‐head [2e–i,l–o,3,4] processes has been established in the presence of catalytic or stoichiometric amounts [3] of transition metals. As far as we know, tail‐to‐tail reductive dimerization of terminal alkynes for the generation of 2,3‐dibranched butadienes hasn't been reported (Scheme 1).…”

Direct Enantioselective Addition of Alkynes to Imines by a Highly Efficient Palladacycle Catalyst

“…Rather than the desired 1,2‐addition, dimerization of the alkynes delivering enyne products took place. This latter reaction type was also optimized providing a regiodivergent access of enynes as recently published by us [11] …”

“…This latter reaction type was also optimized providing a regiodivergent access of enynes as recently published by us. [11] During these early attempts, it was found that the ferrocenediyl bisimidazoline bispalladacycle [FBIP-Cl] 2 [9] showed no catalytic activity in chlorobenzene at 60 °C, neither for 1,2-additions nor for the undesired alkyne dimerizations (Table 1, entry 1). Catalyst activation by silver acetate to remove the four tightly binding chloride bridges in order to facilitate substrate coordination [9] provided the desired 1,2-adduct 3 aA as a side product in 8 % yield (entry 2), yet with high enantiomeric excess (ee = 95 %).…”

Direkte enantioselektive Addition von Alkinen an Imine unter Verwendung eines hocheffizienten Palladacyclus als Katalysator

“…Eine Einkristall-Röntgenstrukturanalyse ergab eine (S)-Konfiguration für das Produkt 3 bD. [13] Die Verwendung von aromatischen Alkinen mit Akzeptor-Substituenten führte zu guten Ausbeuten und nahezu enantiomerenreinen Produkten ( Einträge 7,9,10,11). Ausbeute 3…”