Regiodivergent Copper Catalyzed Borocyanation of 1,3‐Dienes

Abstract

Copper catalyzed multi‐functionalization of unsaturated carbon‐carbon bonds is a powerful tool for the generation of complex molecules. We report a regiodivergent process that allows a switch between 1,4‐borocupration and 4,1‐borocupration of 1,3‐dienes upon a simple change in ligand. The subsequently generated allyl coppers are trapped in an electrophilic cyanation to selectively generate densely functionalized and synthetically versatile 1,2‐ or 4,3‐borocyanation products.

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

“…Then, all possibilities in the borocupration and electrophilic cyanation will be considered and the origins of the regioselectivity will be rationalized. Finally, the results of the Cu/PCy 3 -catalyzed borocyanation of 1,3-diene 1a with N- 9 The borocupration and electrophilic cyanation were calculated to be both irreversible, which thus constitute the regioselectivity-determining steps of the reaction. The origins of the regioselectivity in these steps will be explored in the sections below.…”

“…The computations show that the electrophilic cyanation at C 1 position via transition state TS4a′ is 2.7 kcal/mol higher in energy than that at C 3 position via transition state TS4a (−15.1 kcal/mol of TS4a′ versus −17.8 kcal/mol of TS4a), being in good agreement with the experimental results that 4,1borocupration product 5a was not obtained. 9 Given that the relative stability of INT2a and INT3a is nearly identical, the distortion/interaction analysis 23,24 of TS4a and TS4a′ was employed to gain deeper insights into the origins of the regioselectivity (Figure 4). The results show that the interaction energy of TS4a′ is however 1.6 kcal/mol lower than that of TS4a, and the regioselectivity is mainly caused by the difference in the distortion energies of the INT2a and INT3a moieties.…”

“…The computations show that the 4,3-borocupration is more favored than the 1,2-borocupration by 1.7 kcal/mol (−0.6 kcal/mol of TS1a versus 1.1 kcal/mol of TS1b), 20 which corresponds to a calculated ratio of 18:1 (3a/4a) at the reaction temperature (25 °C), being in good agreement with the experimentally observed ratio of >20:1. 9 The calculated preference of the 4,3borocupration is consistent with the previous experimental study that the borocupration of the monosubstituted alkenes is more favored than that of the 1,1-disubstituted alkenes. 21 The origins of this regioselectivity is mainly attributed to the fact that steric repulsion around the forming Cu−C bond in the borocupration of the C 1 −C 2 double bond is greater than that of the C 3 −C 4 double bond.…”

“…By changing the ligand to PCy 3 , the reversed regioselectivity was observed and the 1,2-borocyantion product 4a was obtained as the major product with a ratio of 10:1 (4a/ 3a). 9 To elucidate the origins of the ligand-controlled regioselectivity, we now turn our attention to the Cu/PCy 3catalyzed reaction. The calculated energy profile of the Cu/ PCy 3 -catalyzed borocyanation of 1,3-diene 1a with N-cyano sulfonamide 2b, along with the optimized geometries of the key transition states, is given in Figure 5 (see the Supporting Information for the results of other possible pathways).…”

“…8 In this regard, Procter and co-workers very recently developed an elegant example of the regioselective borocyanation of 2-arylsubstituted 1,3-dienes 1 catalyzed by the copper complexes (Scheme 1). 9 The significant feature of the reaction is that the regioselectivity of the reaction is governed by the ligand of the copper catalyst. The experiments showed that with the XantPhos ligand, the 4,3-borocyanation products 3 was obtained as the major product.…”