General and Selective Head-to-Head Dimerization of Terminal Alkynes Proceeding via Hydropalladation Pathway

Abstract

A general highly regio- and stereoselective palladium-catalyzed head-to-head dimerization reaction of terminal acetylenes is presented. This methodology allows for the efficient synthesis of a variety of 1,4-enynes as single E stereoisomers. Computational studies reveal that this dimerization reaction proceeds via the hydropalladation pathway.

Transition metal-catalyzed couplings of alkynes to 1,3-enynes: modern methods and synthetic applications

“…39 The authors reported that the combination of TDMPP and bis- N- heterocyclic carbene palladium complex IPr-Pd-IPr ( 131 ) promoted the homocoupling of aryl, heteroaryl, and alkyl alkynes. In contrast to the prior report, ortho -disubstituted substrate 127 reacted smoothly to yield dimer 137 , a result that suggested that the reaction mechanism did not involve the agostic C−H interaction proposed previously.…”

Pseudo‐tetrahedral Rhodium and Iridium Complexes: Catalytic Synthesis of E‐Enynes

“…A plausible mechanism for the dimerization of alkynes by using complex 2 as catalyst precursor is shown in Scheme . Only the hydrometalation path has been considered because this step is typically lower in energy than the carbometalation …”

Regiodivergent Synthesis of 1,3‐ and 1,4‐Enynes through Kinetically Favored Hydropalladation and Ligand‐Enforced Carbopalladation

“…At first, the temporary amide-chelated Pd complex undergoes areversible oxidative addition to give either I or II.I nt he case of the bulkier BrettPhos ligand, the alkyne would be located at the opposite site owing to severe steric hindrance,and carbopalladation would be followed by migration of the alkyne to the g-position of the allenesulfonamide to form s-vinyl-Pd intermediate A.T hen, reductive elimination generates the linear product, regenerating the Pd 0 species.T he occurrence of carbopalladation is supported by the results of the competition reactions,s ince the stabilization of electrondeficient Pd II by an electron-rich alkyne makes it less reactive towards linear product formation (see Figure 1, right). In contrast, when the smaller (o-OMePh) 3 Pi sl igated, I and II can be in equilibrium, which may be attributed to the comparable degrees of steric hindrance of the alkyne,l igand and the sulfonamide group.T hen, since hydropalladation is well known to be kinetically favored, [18] the smaller Ha tom will migrate to the g-position of the allenesulfonamide, leading to the exclusive formation of the branched product via intermediate B according to the Curtin-Hammett principle.F or that reason, the formation of the branched product (3aa)might be 6.4 times faster than that of the linear product (4aa). The8 1% d-incorporation in the branched product (30 %incase of linear product) also supported the occurrence of hydropalladation because the adventitious water present in the reaction mixture has less impact on the deuterium incorporation owing to the kinetically favored hydropalladation pathway.…”