Mechanism and Scope of the Cyanide-Catalyzed Cross Silyl Benzoin Reaction

Abstract

In this work, cross silyl benzoin addition reactions between acylsilanes (1) and aldehydes (2) catalyzed by metal cyanides are described. Unsymmetrical aryl-, heteroaryl-, and alkyl-substituted benzoin adducts can be generated in moderate to excellent yields with complete regiocontrol using potassium cyanide and a phase transfer catalyst. From a screen of transition metal cyanide complexes, lanthanum tricyanide was identified as an improved second-generation catalyst for the cross silyl benzoin reaction. A study of the influence of water on the KCN-catalyzed cross silyl benzoin addition revealed more practical reaction conditions using unpurified solvent under ambient conditions. A sequential silyl benzoin addition/cyanation/O-acylation reaction that resulted in two new C-C bonds was achieved in excellent yield. The mechanism of cross silyl benzoin addition is proposed in detail and is supported by crossover studies and a number of unambiguous experiments designed to ascertain the reversibility of key steps. No productive chemistry arises from cyanation of the more electrophilic aldehyde component. Formation of the carbon-carbon bond is shown to be the last irreversible step in the reaction.

Scope of the Asymmetric Intramolecular Stetter Reaction Catalyzed by Chiral Nucleophilic Triazolinylidene Carbenes

“…25 According to the proposed mechanism, intermediate I results from nucleophilic attack of the carbene into the aldehyde. Subsequent proton transfer affords the acyl anion equivalent II, whose resonance structure is the enolamine, commonly referred to as the Breslow intermediate.…”

Synthesis of Acylsilanes by Copper(I)‐Catalyzed Addition of Silicon Nucleophiles onto Acid Derivatives

“…[1] Such compounds are versatile intermediates in organic synthesis, [2,3] and are used mainly as umpolung reagents for the preparation of carbonyl derivatives, employing the Brook rearrangements. [4] New types of catalysts have also been developed with regard to the activation of acylsilanes in 1,2-benzointype additions and 1,4-Stetter reactions, e.g., thiazolium salts, [5] cyanides [6] and metallophosphites. [7] More recently, new applications of acylsilanes have been established with the addition of enolates, [8] Pd-catalyzed coupling reactions, [9] synthesis of substituted g-lactams, [10] or photochemical transformations.…”

Cyanide‐Catalyzed Additions of Acyl Phosphonates to Aldehydes: A New Acyl Donor for Benzoin‐Type Reactions

“…[5,6] A seminal report by Schowen demonstrated that benzil [1c, Eq. (1)] could be utilized as an acyl donor in benzoin-type reactions.…”