Copper -catalyzed condensation reaction

More recently, 13,14-dimethyldibenzo[6j][4,7]phenanthroline (55) was synthesized by the copper-catalyzed condensation reactions between 1,4-diiodobenzene (52) and 2-aminoacetophenone (53) to give 54 followed by sulfuric acid-promoted cyclization reactions (Scheme 10) [56]. Alternatively, 55 was also prepared by a one-pot procedure involving the ZnCl2-catalyzed reactions between AA -diphenyl-p-phenylenediamine (56) and acetic acid (Scheme 11) [57, 58]. The enantiomers of 55 were separated by a chiral HPLC column and were found to undergo rapid racemization at room temperature. A slower rate of racemization was observed for the 13,14-diethyl derivative 57. The X-ray structure of 57 confirmed the twisted aromatic framework. 

The success of bis(oxazolines) (43) in the copper-catalyzed cyclopropanation reaction has prompted numerous researchers to modify these structures in an attempt to improve the catalysts. To date, none have approached the success and generality exhibited by /erf-butyl bis(oxazoline) (55c) although some afford improved selectivities in specific cases. As a corollary to its success in this reaction, the copper-catalyzed cyclopropanation has taken on the aspects of a testing ground for new bis(oxazoline)-based ligands. The plethora of publications in this area will be summarily condensed in the rest of this section, and emphasis will be placed only on those ligands that provide improvements over 55c and those publications that deal with structural or mechanistic advances. 

Abdel-Jalil and co-workers used a novel copper(II)-catalyzed condensation reaction between anthranilamides and aryl, alkyl, and heteroalkyl aldehydes to generate the corresponding 4(3 -quinazolinones in excellent yields." In one example, treatment of anthranilamide with 2-furaldehyde gave the corresponding 2-substituted quinazolinone in 85% yield. The resulting compound could be used to readily access the antibiotic nitrofurquinazol in just a few short steps. 

Thus, it has been reported that aluminated triazoles can be prepared from the corresponding aUcynides by a copper-catalyzed condensation. The aluminum bound can be further functionalized, leading to 1,4,5-trisubstituted triazoles [150]. No reaction occurs in the absence of copper, and the regioselectivity of the reaction clearly rules out a tandem addition-cyclometalation process (Scheme 61). 

There are many other transition-metal catalyzed coupling reactions that are based on organic halides in aqueous media. One example is the coupling of terminal alkyne with aryl halides, the Sonogashira coupling, which has been discussed in detail in the chapter on alkynes (Chapter 4). An example is the condensation of 2-propynyl or allyl halides with simple acetylenes in the presence of copper salts. 

The same group of authors has recently reported a combination of various palladium- and copper-catalyzed Suzuki, cyanation, and Ullmann condensation reactions for the synthesis of thiophene-based selective angiotensin II AT2 receptor antagonists (Scheme 6.24) [55],... 

Ketal regeneration proceeds step-wise through an enol ether intermediate. This intermediate is capable of several side reactions including a copper catalyzed aldol condensation, heavies formation and addition reactions with hydrochloric acid. Hydrochloric acid addition to l-methoxycyclohexene is of no consequence since this side reaction proved to be thermally reversible under oxycarbonylation reaction conditions. 

It is well known that soluble copper or other transition metals will catalyze Aldol condensation reactions(29). The optimum copper(ll)/palladium(ll) molar ratio is 2.3. Normally, about 1500 ppm palladium is used in the butadiene oxycarbonylation reaction. Under typical oxycarbonylation process conditions, around. 5 mole % l, l-dimethoxycyclohexane is lost to heavies per pass. 

Biacetyl is produced by the dehydrogenation of 2,3-butanediol with a copper catalyst (290,291). Prior to the availability of 2,3-butanediol, biacetyl was prepared by the nitrosation of methyl ethyl ketone and the hydrolysis of the resultant oxime. Other commercial routes include passing vinylacetylene into a solution of mercuric sulfate in sulfuric acid and decomposing the insoluble product with dilute hydrochloric acid (292), by the reaction of acetal with formaldehyde (293), by the acid-catalyzed condensation of 1-hydroxyacetone with formaldehyde (294), and by fermentation of lactic acid bacterium (295—297). Acetoin [513-86-0] (3-hydroxy-2-butanone) is also coproduced in lactic acid fermentation. 

Benzoxazoles are found in a variety of natural products and routinely find use in pharmaceutical research. They are generally made by condensation of a 2-aminophenol with a carboxylic acid or oxidative cylization of an imine intermediate. A mild copper-catalyzed cyclization of o/t/ o-haloanilides to give benzoxazoles 209 has been reported (Scheme 62) <2006JOC1802>. This route is conceptually different to the aforementioned methods in that the starting material is a 2-haloaniline rather than a 2-aminophenol. The reaction conditions tolerate various functional groups in the amide portion of the molecule. 

Condensation with carbonyl compounds. Formation of epoxides from aldehydes by reaction with sulfonium ylides is subject to asymmetric induction. The latter species have been generated from 91, 92, and 93, and also those derived from monoterpenes, e.g., 94 " and 95.- Of course the ylides can be obtained in situ by deprotonation of sulfonium salts or copper-catalyzed decomposition of diazoalkanes (with the carbenoids trapped by the sulfides). 

Importantly, salt-induced peptide formation could provide an abiotic route for the formation of peptides directly from amino acids in concentrated NaCl solutions containing copper ions. Montmorillonite and similar minerals apparently promote the condensation reaction that could have taken place in evaporating tidal pools -Darwin s warm little ponds - where the required salty brine solutions were easily available. Obviously, this is a likely and hence a credible prebiotic scenario. There might a pearl hidden beneath muddy waters. Besides, it is fascinating to assume that the primitive enolase enzyme known to be a highly conserved ancient enzyme could have evolved in an RNA-peptide world. Enolase catalyzes the for enantio-selective carbon-carbon bond addition of water to phosphoenol pyruvate to yield D-2-phospho-glycerate. 

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