Mechanism and Origins of Regioselectivity of Copper-Catalyzed Borocyanation of 2-Aryl-Substituted 1,3-Dienes: A Computational Study

Abstract

Density functional theory calculations were performed to investigate the copper-catalyzed borocyanation of 2-aryl-substituted 1,3-dienes. The computations show that the regioselectivity of the overall reaction is governed by the combination of the inherent regioselectivity of the borocupration and electrophilic cyanation steps. The π-conjugation effect of the 1,3-diene makes the terminal carbon atoms more electrophilic compared with the internal carbon atoms, which coupled with the steric effect results in the 4,3-and 1,2borocupration being intrinsically more favorable than the other possibilities. The steric repulsion around the breaking Cu−C bond was found to be the key factor in determining the regioselectivity of the electrophilic cyanation. The origins of the experimentally observed ligand-controlled regioselectivity were ascribed to the electronic and steric effects. For the bulky XantPhos ligand, the 4,3-borocupration was found to be more favorable than the 1,2-borocupration due to the steric repulsion around the forming Cu−C bond, resulting in the formation of the 4,3-borocyantion product. On the other hand, the reversed regioselectivity with a small PCy 3 ligand is mainly caused by the electronic effect that the π-electron-withdrawing aryl group at the C 2 atom makes the C 1 atom more electrophilic than the C 4 atom, enabling the 1,2-borocupration to be more favorable than the 4,3-borocupration.

Copper(I)‐Catalyzed Asymmetric Conjugate 1,6‐, 1,8‐, and 1,10‐Borylation

“…Of particular utility is the structural information provided through the transition state calculations, which provides insight into the specific interactions that drive the regio‐ and enantioselectivity. It is evident that proximal additions would suffer steric interaction between the dioxinone and the metal substituents [21c, 23] . Additionally, our stereomechanistic analysis highlighted by the insert in Figure 2 shows one important feature dictating the facial selectivity.…”

Copper-Catalyzed Highly Enantioselective 1,4-Protoboration of Terminal 1,3-Dienes

“…[104][105][106][107] In addition, both compound 5a and 6a could originate from this Cu-complex (7a). [106][107][108][109][110][111] Under the optimized reaction conditions, the intermediate 7a could convert into product 5a via a six-membered type transition state. [108][109][110][111][112] Moreover, 7a could be quenched by AcOH to afford compound 6a without forming the desired product 5a (Table 1, entry 6).…”

“…[106][107][108][109][110][111] Under the optimized reaction conditions, the intermediate 7a could convert into product 5a via a six-membered type transition state. [108][109][110][111][112] Moreover, 7a could be quenched by AcOH to afford compound 6a without forming the desired product 5a (Table 1, entry 6). 106,107 Furthermore, the consumption of 1a could induce the low concentration of 7a, which causes the signal of 6a to decrease in the late stage of the reaction process (Scheme 3 and Figure 2, 6a).…”

“…As the key intermediate, 7a affords the desired product 5a via protonation. [108][109][110][111][112] The feasibility of 1 mmol scale reaction was established under standard reaction conditions. The above reaction afforded desired product 5a with 68% yield and 97% ee (Figure 3, (1), and Supporting Information).…”

Beyond Carbon: Enantioselective and Enantiospecific Reactions with Catalytically Generated Boryl- and Silylcopper Intermediates

“… 88 Alternatively, the 1,4-adduct XXIII can also be generated through the isomerization from XXIII since the 1,2-addition has been suggested to be an energetically lower pathway. 89 , 90 …”