Highly Selective Methods for Synthesis of Internal (α-) Vinylboronates through Efficient NHC–Cu-Catalyzed Hydroboration of Terminal Alkynes. Utility in Chemical Synthesis and Mechanistic Basis for Selectivity

Abstract

Cu-catalyzed methods for site-selective hydroboration of terminal alkynes, where the internal or α-vinylboronate is generated predominantly (up to >98%) are presented. Reactions are catalyzed by 1-5 mol % of N-heterocyclic carbene (NHC) complexes of copper, easily prepared from N-aryl-substituted commercially available imidazolinium salts, and proceed in the presence of commercially available bis(pinacolato)diboron [B(2)(pin)(2)] and 1.1 equiv of MeOH at -50 to -15 °C in 3-24 h. Propargyl alcohol and amine and the derived benzyl, tert-butyl, or silyl ethers as well as various amides are particularly effective substrates; also suitable are a wide range of aryl-substituted terminal alkynes, where higher α-selectivity is achieved with substrates that bear an electron-withdrawing substituent. α-Selective Cu-catalyzed hydroborations are amenable to gram-scale procedures (1 mol % catalyst loading). Mechanistic studies are presented, indicating that α selectivity arises from the structural and electronic attributes of the NHC ligands and the alkyne substrates. Consistent with suggested hypotheses, catalytic reactions with a Cu complex, derived from an N-adamantyl-substituted imidazolinium salt, afford high β selectivity with the same class of substrates and under similar conditions.

Copper–NHC complexes in catalysis

“…These potent reagents find many applications, such as in the Suzuki-Miyaura cross-coupling reaction. In 2011, Hoveyda and co-workers published a highly efficient and selective process for the hydroboration of terminal alkynes [67,68]. The N-substituents of NHC ligands allowed to control the selectivity.…”

Cyclodextrin Cavity‐Induced Mechanistic Switch in Copper‐Catalyzed Hydroboration

“…[17] Remarkably, inversions of regioselectivities have been observed, particularly by introducing different copper ligands. [18][19][20][21][22][23] For aryl-substituted terminal alkynes, and with nonbulky ligands, the selectivity is generally in favor of the linear adduct (or -product, Scheme 1).…”

“…Noteworthy, after a round of optimization, [26] we found that the different experimental conditions to get Linear (RT) or Branched (-20°C) derivatives described by Hoveyda were also the most efficient in our case. [18] We then operated a review of various electronic effects on the alkyne aryl group in all ortho, meta and para positions. (α-ICyD)CuCl consistently gave the linear product whereas (-ICyD)CuCl gave the branched compound as the major one.…”

“…The copper-mediated borylation of alkynes is thought to start with activation of the (L)CuCl pre-catalyst by tBuOK to form a (L)Cu-OtBu adduct which reacts with (BPin) 2 to give a (L)Cu-Bpin complex. [15][16][17][18]27,28] Next, the formation of a vinyl copper species resulting from concerted syn borylcupration of the alkyne was proposed. [29] The regioselectivity of the reaction is influenced at this step both by the initial approach of the alkyne on the copper atom to form the -complex (Ia or Ib Scheme 2) and by the TS (IIa or IIb) of the insertion step.…”

“…This "parallel" lateral approach of the alkyne to the NHC-Cu-B bond was extensively investigated by theoretical calculations. [18,30] Generally, less hindered and more electronically rich ligands favor linear product formation, whereas more sterically hindered less electron-donating ligands give branched products. However, this last statement seems to be in contradiction with our results, as the most sterically hindered ligand -ICyD affords linear products, when the larger -CD derivative favors branched compounds.…”