Tsuyoshi Ueda

Palladium‐Catalyzed Reductive Carbonylation of Aryl Halides with N‐Formylsaccharin as a CO Source

Aromatic aldehydes are valuable synthetic intermediates in C C bond-forming reactions. The reduction of carboxylic acids or esters to aldehydes is a commonly used synthetic strategy in spite of its drawbacks, that is, the functional groups that it can be applied to are limited, a relatively low temperature is required, and a two-step procedure involving initial activation of the carboxylic acid prior to the reduction is sometimes necessary. Direct formylation of aryl halides is a single-step alternative transformation which can be employed to form aldehydes. The conventional strategy for this conversion involves halogen–metal exchange by alkyllithium and subsequent addition of formylating agents (e.g., DMF). In this procedure, the reaction requires a stoichiometric amount of the metal reagent, the strong basicity of which limits the scope of functional groups which can be tolerated. An efficient and complementary methodology is the palladium-catalyzed reductive carbonylation of aryl halides, which employs CO gas. Because of the pioneering work by Heck and Schoenberg in 1974, several groups have worked on developing this conversion to enhance its utility as a synthetic tool. However, there are still only a few general protocols for reductive carbonylation, 4] especially in comparison to alkoxyand aminocarbonylations. Recently Beller et al. reported the first industrially applied and efficient palladium-catalyzed reductive carbonylation at 5 bar of synthesis gas (CO/H2 1:1). [5]

Palladium-Catalyzed Carbonylation of Aryl, Alkenyl, and Allyl Halides with Phenyl Formate

Highly efficient palladium-catalyzed carbonylation of aryl, alkenyl, and allyl halides with phenyl formate is reported. This procedure does not use carbon monoxide and affords one-carbon-elongated carboxylic acid phenyl esters in excellent yields. The reaction proceeds smoothly under mild conditions and tolerates a wide range of functional groups including aldehyde, ether, ketone, ester, and cyano groups. Furthermore, a variety of heteroaromatic bromides can be converted to the corresponding phenyl esters in high yields.

Trichlorophenyl formate: highly reactive and easily accessible crystalline CO surrogate for palladium-catalyzed carbonylation of aryl/alkenyl halides and triflates.

The high utility of 2,4,6-trichlorophenyl formate, a highly reactive and easily accessible crystalline CO surrogate, is demonstrated. The decarbonylation with NEt(3) to generate CO proceeded rapidly at rt, thereby allowing external-CO-free Pd-catalyzed carbonylation of aryl/alkenyl halides and triflates. The high reactivity of the CO surrogate enabled carbonylation at rt and significantly reduced the quantities of formate to near-stoichiometric levels. The obtained trichlorophenyl esters can be readily converted to a variety of carboxylic acid derivatives in high yields.

Palladium-Catalyzed Fluorocarbonylation Using N-Formylsaccharin as CO Source: General Access to Carboxylic Acid Derivatives

N-formylsaccharin, an easily accessible crystalline compound, has been employed as an efficient CO source in Pd-catalyzed fluorocarbonylation of aryl halides to afford the corresponding acyl fluorides in high yields. The reactions use a near-stoichiometric amount of the CO source (1.2 equiv) and tolerate diverse functional groups. The acyl fluorides obtained could be readily transformed into various carboxylic acid derivatives such as carboxylic acid, esters, thioesters, and amides in a one-pot procedure.

Construction of Iterative Tetrahydrofuran Ring Units and Total Synthesis of (+)-Goniocin

Cytotoxic acetogenin (+)-goniocin has been synthesized in 17 steps from (R)-O-tritylglycidol. The core structure of the contiguous C22-C10 threo-trans-threo-trans-threo-trans-tris-tetrahydrofuran (THF) ring involving an iterative THF-ring unit was synthesized. An iterative THF ring unit was constructed from an alkenyl-substituted THF ring in four steps including a Pd(II)-catalyzed ring-closing reaction and cross-metathesis. This method is general and allows the preparation of both trans-threo-trans- and trans-threo-cis-THF ring units flexibly.

Imidazole Derivatives as Accelerators for Ruthenium‐Catalyzed Hydroesterification and Hydrocarbamoylation of Alkenes: Extensive Ligand Screening and Mechanistic Study

Imidazole derivatives are effective ligands for promoting the [Ru3(CO)12]‐catalyzed hydroesterification of alkenes using formates. Extensive ligand screening was performed to identify 2‐hydroxymethylated imidazole as the optimal ligand. Neither carbon monoxide gas nor a directing group was required, and the reaction also showed a wide substrate generality. The Ru–imidazole catalyst system also promoted intramolecular hydrocarbamoylation to afford lactams. A Ru–imidazole complex was unambiguously analyzed by X‐ray crystallography, and it had a trinuclear structure derived from one [Ru3(CO)12] and two ligands. This complex was also successfully used for hydroesterification. The mechanism was examined in detail by using D‐ and 13C‐labeled formates, indicating that the hydroesterification reaction proceeds by a decarbonylation–recarbonylation pathway.