Switching between borrowing hydrogen and acceptorless dehydrogenative coupling by base transition-metal catalysts

Abstract

Taking the advantages of sustainability and economy, the borrowing hydrogen (BH) and acceptorless dehydrogenative coupling (ADC) methodologies based on earth-abundant transition-metal catalysts have recently attracted enormous interest in both academia and industry. Novel strategies to achieve switchable synthesis of the BH and ADC products by precise control of the reaction parameters and the catalytic systems are desirable and will significantly promote the field. In this mini-review, we summarized the published work on the switchable synthesis of amine/imine, alcohol/ketone, nitrile/acrylonitrile, and alkane/alkene through BH and ADC pathways, respectively. Specifically, we discussed the origin of the product-switching.

Introduction

The construction of C–C and C–N bonds belongs to one of the essential transformations in organic synthesis of products of high values [1]. One preeminent synthetic strategy is borrowing hydrogen (BH), which takes advantage of transfer hydrogenation to avoid the use of hydrogen gas and provide an attractive environmentally benign and atom- and process-efficient process, with water as the sole byproduct [[2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15]]. Alcohols, which are readily available, less toxic, and obtainable from biomass feedstock can be directly utilized to replace the toxic and mutagenic alkylating agents such as alkyl halides and alkyl sulfonates in the conventional synthetic methods [16].

The early examples of BH can be dated back to the early 1980s [17,18], and the term “borrowing hydrogen” was first defined by Whittlesey, Williams, and coworkers in 2004 [19]. Since the discovery of the BH methodology, the development of reactive catalysts based on precious transition-metals, e.g., Ir, Ru, Rh, Pd, etc. Have been the focus [[12], [13], [14], [15]]. It is only around early 2010s that with the increasing concerns on the sustainability and economy, more research efforts have been shifted towards the earth-abundant and less expensive base metal analogs using Fe, Co, Mn, and Ni, etc. [20]. Some base metals are less toxic. For example, as the first and third most abundant transition-metal in the Earth's crust, respectively, Fe and Mn impose minimal environmental and toxicological impacts.

The BH falls into the category of cascade reaction, in which a consecutive series of reactions lead to the final products [21]. In the general BH process, alcohols are first dehydrogenated with the catalyst taking two hydrogens forming [MH₂] (Scheme 1). The in-situ formed reactive carbonyl intermediates, e.g., aldehydes and ketones, undergo condensations with nucleophiles to generate the unsaturated intermediates such as imines or alkenes, with the elimination of water. In the last step, the catalyst returns the “borrowed” hydrogens and reduces the unsaturated intermediates, affording the desired saturated products (Scheme 1, in red). In an alternative pathway, the hydrogen gas can be released from the “hydrogenated” catalyst, thus the reaction stops at the level of the unsaturated compounds. This process is recognized as the acceptorless dehydrogenative coupling (ADC) as no external hydrogen acceptors are employed (Scheme 1, in blue) [[2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15],22,23]. BH and ADC have recently attracted increasing interest in both academia and industry due to the high sustainability and cost efficiency of these methods.

Recently, several excellent reviews have appeared on the general BH and ADC methodologies using homogeneous base transition-metal catalysts [[2], [3], [4], [5], [6], [7], [8], [9], [10], [11]]. It is still a challenge to efficiently tune the selectivity, e.g., the ADC products are often identified as the major side products in the synthesis of the BH products and vice versa [[2], [3], [4], [5], [6], [7], [8], [9], [10], [11], [12], [13], [14], [15]]. In this mini-review, we will focus on a new and unique direction by surveying the novel synthetic methods that can be applied to achieve switchable synthesis of the BH and ADC products. Although still scarce in the literature, these protocols exhibit the appealing control of the outcomes of the reactions by precisely adjusting the catalytic parameters, which is imperative from both practical and mechanistic points of view.

Herein, we will summarize the state-of-the-art switchable synthesis of a large variety of valuable products, such as amine/imine, alcohol/ketone, nitrile/acrylonitrile, and alkane/alkene, through the BH and ADC processes, respectively, mediated by homogeneous base transition-metal catalysts. We will focus on the design principles of the multifunctional catalytic systems for the product-switching. The current challenges and opportunities will be highlighted. Lastly, future development directions of this chemistry will be discussed.

BH/ADC switching by precious metal catalysis is not the focus of this mini-review. Such examples are surprisingly rare, and we will briefly mention them here. Interesting reviews on the general precious metal catalyzed BH and ADC reactions are available [[12], [13], [14], [15]]. Representative heterogeneous and transition-metal-free cases will also be briefly discussed.