Mechanistic Investigation of the Nickel-Catalyzed Carbonylation of Alcohols

Abstract

The carbonylation of alcohols represents a straightforward and atom-efficient methodology for the preparation of carboxylic acids. It is desirable to perform these reactions under precious metal-free and low-pressure conditions, with regioselectivity control. In this work, we present a detailed mechanistic study of a catalytic system based on NiI2, which can carbonylate benzylic alcohols in a highly regioselective manner to the corresponding branched carboxylic acids, core motifs for nonsteroidal drugs. The combination of catalytic amounts of nickel and iodide is crucial for efficient catalytic and regioselective conversion. Quantum-chemical computations were used to evaluate the underlying mechanistic processes. They revealed that a combination of two mechanisms is responsible for the observed reactivity and that the oxidative addition of alkyl halides to the Ni(0) species follows a radical oxidation pathway via two one-electron steps.

Revisiting Nickel-Catalyzed Carbonylations: (Unexpected) Observation of Substrate-Dependent Mechanistic Differences

“…Even though the transformation of the alcohol to the alkyl iodide species is a simple S N 1 reaction, which should favor the formation of tert -butyl iodide ( t BuI) from t BuOH, one could envision that isobutyl iodide ( i BuI) can also be formed, which would then be converted to isovaleric acid. In our previous study, we have shown that cyclohexyl carboxylic acid can be obtained in roughly the same yield both from cyclohexanol with NiI 2 and iodocyclohexane in cyclohexanol (1:9) and Ni­(cod) 2 (cod = 1,5-cyclooctadiene) . If the reaction under investigation follows the same pathway, this separation of reaction steps needs to be possible as well.…”

“…The previously developed, radical-based mechanism builds on the conversion of alcohol to the corresponding alkyl iodide, which is then carbonylated with CO (see Scheme ). The investigated catalytic cycle starts from the diphosphine-dicarbonyl-nickel(0) complex 1 that is formed via the in situ reduction of NiI 2 in the presence of TBP and CO. After the initial phosphine dissociation, 1 forms an adduct with the tert -butyl halide 2- t Bu or isobutyl halide 2- i Bu (Δ G 453 = 107.3 and 110.5 kJ mol –1 , respectively). Barrierless homolytic cleavage of the C–I bond in 2- t Bu/2- i Bu leads to the formation of 3 and the corresponding t Bu or i Bu radical ( 3 + t Bu • : Δ G 453 = 94.4 kJ mol –1 ; 3 + i Bu • : Δ G 453 = 120.8 kJ mol –1 ), which can quickly recombine to form Ni­(II) complex 4- t Bu (Δ G 453 = 135.6 kJ mol –1 ) or 4- i Bu (Δ G 453 = 125.4 kJ mol –1 ), depending on the substrate.…”

“…This highlights the attractiveness of a method under less harsh conditions for the direct synthesis of free carboxylic acids with branched selectivity. In a previous study on the carbonylation of benzylic and aliphatic alcohols, we found that the combination of NiI 2 with P­( n Bu) 3 (tri- n -butylphosphine, TBP) and LiI affords the desired carboxylic acids in good to excellent yields with the exclusive formation of the respective branched acids in the case of benzylic alcohols . Based on our findings regarding the mechanism of these Ni-catalyzed carbonylation reactions, we hypothesized that the same system might be a potent candidate for the carbonylation of tertiary alcohols (see Scheme ).…”

Structure-Reactivity Relationships of Buchwald-Type Phosphines in Nickel-Catalyzed Cross-Couplings

“…Over the past decade, Buchwald-type phosphines have also found successful application in a limited number of Nicatalyzed cross-coupling reactions (Figure 1C). [17][18][19][20][21][22][23][24][25] One of the first reports came from our lab in 2011 with the development of a Ni-catalyzed cross-coupling of styrenyl epoxides and boronic acids, where BrettPhos was identified to be the most effective ligand in the transformation. 18 The Watson and Crudden labs have also reported the use of Buchwald-type phosphines in Nicatalyzed-cross coupling reactions of naphthylic pseudohalides.…”

Nickel N-Heterocyclic Carbene Catalysts for Ester Carbonylation

“…Nickel complexes were once considered promising homogeneous carbonylation catalysts, as reflected in patents (17)(18)(19)(20)(21)(22) and the peer-reviewed literature (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). There are inherent economic advantages of an abundant and inexpensive nickel catalyst: a metric ton of nickel can cost the same as a troy ounce of rhodium.…”