Aryl chlorides aminocarbonylations

Scheme 1 Microwave-promoted aminocarbonylations of aryl chlorides using Mo(CO)g as a solid carbon monoxide source...

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... 

Larhed s group developed the microwave-promoted aminocarbonylation of aryl chlorides using Mo(CO)e as a solid carbon monoxide source [226-228]. This procedure offers aryl chlorides that rapidly transformed into a variety of benzamides (Scheme 2.29). Noteworthy features of this microwave method include the use of commercially available [(f-Bu)3P]HBF4 to activate the strong Ar-Cl bond impressive results with sluggish aniline and ferf-butylamine reactants air tolerance short reaction times and the use of Mo(CO)g as a solid carbon monoxide source. 

SCHEME 3.1 Palladium-catalyzed aminocarbonylation of aryl chlorides. 

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. 

Aryl Halide Carbonylations. Palladium-catalyzed carbony-lation of aryl halides is an efficient way to produce carboxylic acid derivatives. Aminocarbonylation of aryl chlorides has heen performed using Mo(CO)6 as the carbon monoxide source and a catalyst derived from TTBHBF4 andpalladacycle 1 under microwave irradiation (170 °C). Tbe catalyst system was also applied to the carbonylation of 4-chloro-l-trifluoromethylbenzene in hutanol to... 

Thereafter, a full paper describing aminocarbonylations in water was published [29]. In addition to presenting the results achieved with aryl bromides, aminocarbo-nylation protocols for aryl iodides and aryl chlorides were also disclosed. More than 90 successful aminocarbonylations in water were presented (Scheme 4.14), including a medicinal chemistry application where this amidation procedure was used to synthesize a potent HIV-1 protease inhibitor from the aryl bromide (Scheme 4.15) [29]. 

Wu, X., Ekegren, J.K. and Larhed, M. (2006) Microwave-promoted aminocarbonylation of aryl iodides, aryl bromides and aryl chlorides in water. Organometallics, 25, 1434-1439. 

All substrates mentioned in the previous chapter easily undergo palladium-catalyzed aminocarbonylation also. It should be mentioned that even allylic carbonates instead of halides could be converted into carboxamides by this method, as it vas demonstrated during the total synthesis of antillatoxin [94]. The use of aryl chlorides is somewhat restricted owing to the low reactivity ofthese type of substrates in oxidative addition to palladium(O), as well as the competitive amination observed, for example, in the reaction of 1-chloroisoquinoline [95]. Functionalization of a great number of pharmaceutically important skeletons, for example, steroids [96-99], tropenes [100], benzodiazepines [101], indoles [102], benzo[c[quinolizine derivatives [103], and quinolones [104], have been carried out. 

Scheme 17.46 Aminocarbonylation of aryl chlorides using a bidentate phosphine ligand.

Scheme 4 Fast aminocarbonylation of aryl iodides, bromides and chlorides in neat water...

Hydroxymethylaziridines of this type can also be induced to engage in a Lewis acid-mediated rearrangement to the corresponding aminocarbonyl compound. Thus, the bicyclic tosylaziridine 172 provided 173 in near quantitative yield when treated with zinc bromide in methylene chloride. The rearrangement involves a stereospecific 1,2-migration of the aryl group. The latter compound was used as a key intermediate in the synthesis of mesembrine <03OL2319>. 

One of the major problems encountered in this synthesis is the difficulty of obtaining the starting materials (either the a-aminocarbonyl compounds or their acylated derivatives). The former may be prepared by Neber rearrangement of ketoxime tosylates with a base such as ethoxide or pyridine.46 a-Acylamino carbonyl compounds can be prepared directly by the reductive acetylation of oximino ketones.28 38 Balaban and his collaborators47-60 have developed an excellent method for the synthesis of a-acylamino ketones (5). They are obtained in yields of 50-90% by the reaction of azlactones (2-aryl-5-oxazolone, 4) with aromatic hydrocarbons in the presence of aluminum chloride under Friedel-Crafts conditions the reaction may proceed either intermolecularly or intramolecularly. 

Aminocarbonylations of aryl iodides in the absence of carbon monoxide and a base were reahzed in 2002 by a combination of phosphoryl chloride with N,N-di-methylformamide (DMF) [120]. With the assistance of 2.5 mol% Pd2(dba)3, good to high yields of amides were obtained in toluene at 120 °C (Scheme 2.9). The generated Vilsmeier reagent was suggested to be essential for the reaction to take place. 

Palladium bromide is also an efficient Pd(0) catalyst precursor for the aminocarbonylation of benzyl chlorides (eq 46), car-bonylative Heck reaction of aryl bromides with vinyl ethers (eq 47), and carbonylation of halogenoalkynes (eq 48). ... 

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