C−Boron Enolates Enable Palladium Catalyzed Carboboration of Internal 1,3‐Enynes

Abstract

A new family of carbon-bound boron enolates, generated by a kinetically controlled halogen exchange between chlorocatecholborane and silylketene acetals, is described. These CÀboron enolates are demonstrated to activate 1,3-enyne substrates in the presence of a Pd 0 /Senphos ligand complex, resulting in the first examples of a carboboration reaction of an alkyne with enolate-equivalent nucleophiles. Highly substituted dienyl boron building blocks are produced in excellent site-, regio-, and diastereoselectivity by the described catalytic cis-carboboration reaction.Alkenyl boronates are versatile building blocks in synthetic chemistry. [1] The ability of organoboron compounds to engage in Suzuki-Miyaura cross couplings [2] and to transform into various derivatives [3] have made alkenyl boronates highly appealing in organic synthesis. In this context, numerous approaches [4] have been developed to synthesize di- [5] and tri- [6] substituted alkenyl boronates. The synthesis of tetrasubstituted alkenyl [7] boronates on the other hand, particularly in regioselective and stereoselective fashion, has been more challenging. [8] Pioneering work by Suginome et al. (Scheme 1 a) established the nickel-or palladium catalyzed intramolecular boryl migration approach using alkyne substrates tethered with boryl moiety. [9] Similarly, nickel and palladium catalyzed intermolecular carboboration of alkynes with various carbon sources (Scheme 1 b) was reported. [10] More recently, copper-catalyzed three-component coupling of an alkyne, B 2 pin 2 , and an electrophile (Scheme 1 c) has received attention. [11] Despite these advances, carboboration reactions are still relatively limited in substrate scope and generality. In particular, stereoselective carboborations to produce tetrasubstituted alkenes often face regio-and dia-stereoselectivity issues for internal unsymmetrical alkynes. [11a-e] We recently reported the trans-hydroboration and trans-cyanoboration of 1,3-enynes catalyzed by a 1,4-azaborine biaryl phosphine (Senphos)-Pd complex. [12] An unusual outer-sphere oxidative addition mechanism [13] (a cooperative activation of the 1,3-Scheme 1. Regio-and stereoselective synthesis of tetrasubstituted alkenyl boronates.

A Syn Outer-Sphere Oxidative Addition: The Reaction Mechanism in Pd/Senphos-Catalyzed Carboboration of 1,3-Enynes

“…Overall, the inner-sphere mechanism is predicted to be energetically unfeasible and is not consistent with the reported relatively mild catalytic ciscarboboration reaction conditions. [13] We then examined the outer-sphere oxidative addition mechanism (Scheme 2a-2b), where the palladium center is not directly involved in the cleavage of the C-B bond of the C-boron enolate. As illustrated in Figure 2, this mechanism starts with the enyne coordinating to the palladium center.…”

“…In 2021, our group reported a new cis-selective enolate carboboration reaction (Scheme 1d) of internal 1,3-enynes accompanying the discovery of a new family of carbon-bound boron enolates (C-boron enolates) generated by a kinetically controlled halogen exchange between chlorocatecholborane and silylketene acetals. [13] These unquaternized C−boron enolates [14] are demonstrated to activate 1,3-enyne substrates in the presence of a Pd 0 /Senphos ligand complex. A remarkable feature is that this transformation provides access to the highly substituted dienyl boron building blocks in high site-, regio-, and diastereoselectivity.…”