Aminocarbonylation palladium-catalyzed

In this chapter we describe a novel, safe and efficient large-scale synthetic approach to tricycle thienobenzazepines. The key steps in the synthesis include a chemoselective hydrogenation of an aryl-nitro functionality in the presence of a 3-bromo thiophene and a subsequent palladium-catalyzed intramolecular aminocarbonylation telescoped sequentially after simple catalyst and solvent exchange. 

Scheme 6.46 Palladium-catalyzed aminocarbonylations using molybdenum hexacarbonyl as a solid source of carbon monoxide.

Scheme 6.48 Palladium-catalyzed aminocarbonylations using formamides as sources of carbon monoxide.

In a more recent report, Larhed and coworkers have presented microwave-mediated fluorous reaction conditions for palladium-catalyzed aminocarbonylations [100]. 

Starting with bromoallenes 133, nucleophilic substitution supported by the use of cuprous cyanide lead to cyanoallenes of type 134 (Scheme 7.22) [126, 131, 181]. Pro-pargyl precursors and also cumulenes of type 133 can be utilized for palladium-catalyzed aminocarbonylation to give allenic amides 135 (cf. Section 7.2.6) [182]. 

Palladium-catalyzed aminocarbonylations, using solid Mo(GO)6 as the carbon monoxide source, have been performed under microwave-assisted conditions, with both 5-bromopyrimidine and 2-substituted-5-bromopyrimidines 273 <2007TL2339>. 

As stated above, aliphatic amines are potent ligands for electrophilic transition metals and are efficient catalyst poisons in attempted alkene animation reactions. However, tosylation of the basic amino group greatly reduces its complexing ability, yet does not compromise its ability to nucleophilically attack complexed alkenes. Thus, a variety of alkenic tosamides efficiently cyclized under palladium(II) catalysis producing N-tosylenamines in excellent yield (equations 17 and 18).32 Again, this alkene amination proceeded through an unstable a-alkylpalladium(II) species, which could be intercepted by carbon monoxide, to result in an overall aminocarbonylation of alkenes. With ureas of 3-hydroxy-4-pentenyl-amines (Scheme 7), this palladium-catalyzed process was quite efficient but it was somewhat less so with... 

Palladium-catalyzed aminocarbonylation of alkynes followed by cyclization produced furans with different substitution pattern in good yields <07S4247>. 

Palladium-catalyzed carbonylation of heteroaryl halides provides a quick entry to heteroaryl carbonyl compounds such as heteroaryl aldehydes, carboxylic acids, ketones, esters, amides, a-keto esters, and a-keto amides. In addition, Pd-catalyzed alkoxycarbonylation and aminocarbonylation are compatible with many functional groups, and therefore have advantages over conventional methods for preparing esters and amides [78]. 

Gabriele et al. reported that the 2-oxazolidinones 462 were synthesized by the palladium-catalyzed oxidative carbonylation of the 2-amino- 1-alkanols 461 (Scheme 144).206 The aminocarbonyl palladium complex 463 is formed as an intermediate, and subsequent ring closure gives 462. 

The group also reported DME in the presence of potassium tert-butoxide to be an efhcient source of carbon monoxide and dimethyl-amine in palladium-catalyzed aminocarbonylation (Heck carbonylation Scheme 25.2D). The addition of excess amines to the reaction mixture provided good yields of the corresponding aryl amides. The reaction proceeded smoothly with bromobenzene and more electron-rich aryl bromides, but not with electron-deficient aryl bromides. 

Microwave-mediated fluorous reaction conditions for palladium-catalyzed aminocarbonylations have been discussed in a more recent report [101]. A set of aryl halides was reacted with carbonyl hydrazides and molybdenum hexacarbonyl [Mo(CO)e] as source of carbon monoxide, with fluorous triphenylphosphine (F-TPP) as ligand and the perfluorocarbon liquid FC-84 as perfluorinated solvent (Scheme 16.67). 

In 2008, BeUer and coworkers reported catalytic and stoichiometric synthesis of novel 3-aminocarbonyl-,3-alkoxycarbonyl-, and 3-amino-4-indolyl-maleimides [162]. For instance, t-butyl ester 117 was prepared in 29% yield from 3-bromo-4-indolyl-maleimide 116 under the palladium-catalyzed carbOTiylation conditimis using f-butanol as the solvent and TMEDA as the base. 

Palladium-catalyzed aminocarbonylations of alkenyl phosphates have been investigated using Mo(CO)6 as a solid carbon monoxide source. The reactions afforded a wide variety of acrylamides (78) after 20 min of microwave irradiation in moderate to good yields (Scheme 16). ... 

Scheme 2.10 Palladium-catalyzed aminocarbonylation of aryl bromides...

More recently, a solid-phase palladium-catalyzed aminocarbonylation of aryl bromides or iodides utilizing molybdenumhexacarbonyl (Mo(CO)6) as the carbon monoxide source was presented [125]. Compared to previous carbonylations with metal carbonyl compounds, these reactions proceeded under mild conditions without the presence of microwave irradiation. 

The scope of aminocarbonylations was extended by the works from various groups. For example, Skoda-Fbldes and Kollar studied the carbonylation reactions of ferrocene derivatives in the presence of Pd(OAc)2/PPh3 [126-128]. Ferrocene amides and novel ferrocene a-ketoamides were synthesized in good yields based on palladium-catalyzed aminocarbonylation or double carbonylation of iodofer-rocene at 40-50 bar of CO. The double-carbonylated products were favored at 40-60 °C and amides were produced almost exclusively at 100 °C, as the selectivity of the reaction with less sterically hindered secondary amines is highly dependent on the reaction temperature. Analogous aminocarbonylation reactions of l,l -diiodoferrocene led to I -iodo-ferrocenecarboxamides and I -iodo-ferro-ceneglyoxylic amide-type products. 

More recently, a microwave-promoted palladium-catalyzed aminocarbonyla-tion of (hetero)aryl halides (X = I, Br, Cl) using Mo(CO)e and allylamine as a nucleophile was also described [190, 191]. Remarkably, no side products resulting from the competing Heck reaction were detected. Importantly, this was the achievement that aminocarbonylation was realized on a larger laboratory scale (25 mmol) starting from 4-iodoanisole (Scheme 2.18). 

Perry s group developed a palladium-catalyzed aminocarbonylation of activated aryl chlorides under low CO pressure and in the presence of iodide salt (KI, Nal) [212], Moderate to excellent yields of amides were prepared from activated... 

Like alkoxycarbonylation, aminocarbonylation, and hydroxycarbonylation, the palladium-catalyzed reductive carbonylation reaction was originally discovered by Schoenberg and Heck in 1974 [15]. In the presence of a relatively large amount of [PdX2(PPh3)2l as a catalyst under 80-100 bar of synthesis gas and at 80-150 °C, aryl and vinyl bromides or iodides were converted into the corresponding aldehydes in good yields (Table 3.1). 

In 1999, Hayes and colleagues reported the synthesis of SB-214857, a potent GP nb/nia antagonist, which had been proposed for clinical trials for the prevention of secondary thrombotic events such as heart attack and stroke [85]. 4-Bromo-l-fluoro-2-methylbenzene was used as a starting material, and palladium-catalyzed aminocarbonylation was appUed for the preparation of one of the intermediates (Scheme 10.15). Carey s group did the synthesis from 2-nitrobenzyl alcohol, and palladium-catalyzed aminocarbonylation was applied [86, 87]. 

The potential of palladium-catalyzed aminochlorination reactions of alkenes dates back to their isolation as side products in aminocarbonylation reactions under copper(II)dichloride cocatalysis [47d]. These reactions were later developed further using copper(II) salts as co-oxidants or reoxidants, respectively, and concomitantly as halide sources. For example, Chemler showed that various aminohalogenation reactions proceed under palladium catalysis in the presence of potassium carbonate as base in moderate to excellent yields in the presence of an excess of the copper oxidant [80]. Both five- and six-membered rings 115 and 116 were formed under these conditions from allyl anilines 114 (Scheme 16.28). Among other examples... 

Isoindole-l,3-diones, better known as phthalimides, are key structural units of a variety of biologically important compounds, many of which are pharmaceutically significant. In 2008, Larock and co-worker developed a palladium-catalyzed aminocarbonylation of o-halobenzoates to produce... 

The extensive work carried out by Beller in recent years has contributed to the field with a series of interesting examples, most of them based on the system palladium/di-1 -adamantyl- -butylphosphine (BuPAdj). Thus, they reported the use of ammonia as the nitrogen source for the palladium-catalyzed aminocarbonylation of aryl halides, providing a straightforward method to prepare primary amides with excellent applicability and functional group tolerance [4]. In the same group, the first carbonylative C—H activation reactions of heteroarenes to form diaryl ketones 4 were developed [5], A series of nonpreactivated heteroarenes 3 (oxazoles, thiazoles, and imidazoles) were successfully carbonylative coupled to a wide range of aryl iodides (Scheme 3.2). To avoid the formation of the noncarbonylative... 

J. R. Martinelli, T. P. Clark, D. A. Watson, R. H. Munday, S. L. Buchwald, Angew. Ghent. Int. Ed. 2007, 46, 8460-8463. Palladium-catalyzed aminocarbonylation of aryl chlorides at atmospheric pressure the dual role of sodium phenoxide. 

X.-F. Wu, H. Neumann, M. Beller, Ghent.-Eur. J. 2010, 16, 9750-9753. Selective palladium-catalyzed aminocarbonylation of aryl hahdes with CO and ammonia. 

Carbonylative Amination Among cross-coupling reactions, palladium-catalyzed aminocarbonylation is an interesting regioselective procedure to prepare amides [73]. The methodology consists of three-component coupling of aryl or alkynyl haUdes, primary/secondary amines, and carbon monoxide. 

Cunico and Pandey reported the palladium-catalyzed preparation of a-aryl tertiary amides using benzylic halides and carbamoylsilane [87], and, in this report, a disadvantage of using aminocarbonylation of benzyl halides was also described [90]. Accordingly, to expand the scope of this chemistry, we next focused on the use of benzylic organometallic reagents to develop a facile route for the synthesis of a-aryl tertiary amides. Since the appropriate benzylzinc halides were easily prepared via the direct insertion of highly active zinc, they were employed in the... 

---