Manganese(I)-catalyzed adjacent C-H allylation of benzoic acid derivatives

Manganese(I)-catalyzed adjacent C-H allylation of benzoic acid derivatives
Recently, the group of Lukas J. Gooßen at Ruhr-Universität Bochum, Germany, reported a strategy for the Mn(CO)5Br-catalyzed o-octyl C-H allylation of aromatic carboxylic acid esters using neocuproine reagent (neocuproine) as a ligand. In this case, a highly selective allylation reaction was achieved by using only a simple directing group and catalyst. In addition, the guide group could be easily removed by an in situ decarboxylation reaction, which led to the synthesis of a series of allyl aryl derivatives in a regioselective manner. The related research results were published in Angew. Chem. Int. Ed. (DOI: 10.1002/anie.202301839).

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Allyl aromatic skeletons are widely used in various fragrance industries, pharmaceuticals, natural products and materials science. Traditionally, cross-coupling reactions of prefunctionalized substrates with organometallic reagents or Friedel-Crafts-type reactions are common methods for introducing allyl substituents (Scheme 1). In both cases, the mode of substitution is determined by the intrinsic reactivity of the aromatics in the pre-functionalization step or C-H allylation.
In recent years, chemists have also developed several metal-catalyzed guided C-H allylation reactions that can lead to allylic aromatic derivatives complementary to the above substitution patterns. However, there are problems with the introduction and removal of complex guiding groups, which makes the C-H functionalization strategy too cumbersome. In this regard, simple carboxylic acid esters are highly desirable directing groups and carboxylic acid ester directing groups can be removed at a later stage by in situ decarboxylation or can be subjected to further derivatization. Although chemists have developed several carboxylate-directed C-H functionalization reactions, most require the use of expensive transition metal catalysts.
Recently, Lukas J. Gooßen’s group reported a manganese(I)-catalyzed reaction for the adjacent C-H allylation of benzoic acid derivatives.
Initially, the authors proposed a rational reaction mechanism (Scheme 2).
First, in the presence of an organometallic base (e.g., dimethylzinc), benzoic acid should be irreversibly deprotonated and the methyl group should displace the bromine atom to produce the ligand-stabilized manganese(I) catalyst A. The reaction is then carried out in the presence of an organometallic base (e.g., dimethylzinc).

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Subsequently, the release of methane from complex A generates metallocyclic intermediate B. Intermediate B can be coordinated to the allyl acetate substrate to generate complex C. The double bond in complex C should be inserted into the Mn(I)-C bond to generate complex D. Elimination of complex D by β-oxygen gives the target product. Meanwhile, methylation using dimethylzinc and ligand exchange with zinc benzoate can convert complex E into active catalyst A.
Next, the authors performed an extensive screening of the reaction conditions using 4-fluorobenzoic acid 1 and allyl acetate 2 as model substrates
The screening results showed that when MnBrCO5 was used as the catalyst, ZnMe2 as the base, neocuproine reagent (neocuproine) as the ligand, and THF as the solvent, the product 3 could be obtained in 80% yield.In addition, quantitative decarboxylation could be achieved by adding copper(I) oxide to the solution of NMP/quinoline and heating under microwave at the end of allylation.
After obtaining the optimal reaction conditions described above, the authors extended the substrate range (Table 2).

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First, benzoic acid substrates containing a range of different electrical substituents were successfully reacted to obtain the corresponding products 3, 7-19 and 21-22 in 57-83% yields. Polycyclic aromatic hydrocarbons, as well as heterocyclic substituted carboxylic acid derivatives, were also suitable substrates, and the corresponding products 20 and 23-26 were obtained in 47-76% yields.
Next, various substituted allyl acetates, were also able to undergo the reaction successfully, obtaining the corresponding products 27-34 in 54-77% yields.
In addition, a series of allyl aromatic derivatives 35-48 were obtained in 42-81% yields via a one-pot tandem reaction of allylation/decarboxylation.
To further demonstrate the utility of this C-H allylation reaction, the authors combined C-H allylation with in situ hydroacylation to synthesize the corresponding lactone derivatives 49-51 in 60-69% yields (Scheme 3).
Finally, the authors investigated the reaction mechanism (Scheme 4).
First, deuterium substitution experiments showed that C-H metallization is the first step in the catalytic cycle and that the C-H insertion is irreversible (Scheme 4a and Scheme 4b).
Secondly, KIE experiments showed that the C-H insertion process is the decisive step of the reaction (Scheme 4c).
In addition, a control experiment using allyl benzoate instead of a mixture of allyl acetate and benzoic acid ruled out a reaction pathway through allyl benzoate (Scheme 4d).
Summary
The reaction is characterized by mild reaction conditions, a wide range of substrates, and high functional group compatibility.
In addition, the utility of the reaction was further demonstrated by combining the C-H allylation with in situ decarboxylation or in situ hydroacylation reactions.

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