Transition metal catalysts ketone arylation

The insight that zinc ester enolates can be prepared prior to the addition of the electrophile has largely expanded the scope of the Reformatsky reaction.1-3 Substrates such as azomethines that quaternize in the presence of a-halo-esters do react without incident under these two-step conditions.23 The same holds true for acyl halides which readily decompose on exposure to zinc dust, but react properly with preformed zinc ester enolates in the presence of catalytic amounts of Pd(0) complexes.24 Alkylations of Reformatsky reagents are usually difficult to achieve and proceed only with the most reactive agents such as methyl iodide or benzyl halides.25 However, zinc ester enolates can be cross-coupled with aryl- and alkenyl halides or -triflates, respectively, in the presence of transition metal catalysts in a Negishi-type reaction.26 Table 14.2 compiles a few selected examples of Reformatsky reactions with electrophiles other than aldehydes or ketones.27... 

Among common carbon-carbon bond formation reactions involving carbanionic species, the nucleophilic substitution of alkyl halides with active methylene compounds in the presence of a base, e. g., malonic and acetoacetic ester syntheses, is one of the most well documented important methods in organic synthesis. Ketone enolates and protected ones such as vinyl silyl ethers are also versatile nucleophiles for the reaction with various electrophiles including alkyl halides. On the other hand, for the reaction of aryl halides with such nucleophiles to proceed, photostimulation or addition of transition metal catalysts or promoters is usually required, unless the halides are activated by strong electron-withdrawing substituents [7]. Of the metal species, palladium has proved to be especially useful, while copper may also be used in some reactions [81. Thus, aryl halides can react with a variety of substrates having acidic C-H bonds under palladium catalysis. 

Since the publication by Bolm et al. [3], in 2001, of a review on catalytic asymmetric arylation reactions (Scheme 7.1), many innovative and practical processes have been developed in this area. In this chapter, which concerns the arylation of carbonyl groups (aldehydes, ketones, etc.) and the most important advances that have taken place in the last 10 years or so, enantioselective and nonasymmet-ric arylation of carbonyl groups wHl be discussed, taking into account the different transition-metal catalysts applied. 

Over the last few years, great advances have been made on the a-arylation of carbonyl compounds catalyzed by transition-metal catalysts. A large number of carbonyl compounds, such as ketones, aldehydes, esters, and amides, can be coupled with electron-neutral, electron-rich, electron-poor. 

In 2003, an extremely fast protocol for the cobalt carbonyl mediated formation of symmetric diaryl ketones from aryl halides was disclosed by Larhed and coworkers [38]. Microwave irradiation of aryl iodides and Co2(CO)g in acetonitrile for 10 s or less was enough to produce high yields (57-97%) of symmetric diaryhnethanones (Scheme 4.25). Please note that the Co2(CO)8-mediated chemistry was performed without an additional transition metal catalyst. 

When arylhydrazones of aldehydes or ketones are treated with a catalyst, elimination of ammonia takes place and an indole is formed, in the Fischer indole synthesis.515 Zinc chloride is the catalyst most frequently employed, but dozens of others, including other metal halides, proton and Lewis acids, and certain transition-metals have also been used. Arylhydrazones are easily prepared by the treatment of aldehydes or ketones with phenylhydrazine (6-2) or by aliphatic diazonium coupling (2-7). However, it is not necessary to isolate the arylhy-drazone. The aldehyde or ketone can be treated with a mixture of phenylhydrazine and the catalyst this is now common practice. In order to obtain an indole, the aldehyde or ketone must be of the form RCOCH2R (R = alkyl, aryl, or hydrogen). 

The transition metal catalyzed asymmetric addition of aryl organometallic reagents to aldehydes, ketones, and imines has provided efficient access to chiral aryl alcohols or aryl amines [89]. Arylboronic acids are less toxic, stable toward air and moisture, and tolerant towards a variety of functional groups, and are ideal reagents for the addition to aldehydes. However, when Sakai et al. [90] attempted the enantioselective Rh-catalyzed addition of phenylboronic acid to naphthaldehyde, only 41% ee was obtained. Chiral spiro phosphite complex (S)-18c was found to be an efficient catalyst for asymmetric addition reactions of arylboronic acids to aldehydes, providing diarylmethanols in excellent yields (88-98%) with up to 87% ee (Scheme 30) [20c]. 

A proposed mechanism, shown in Scheme 1, involves a six-member cyclic transition state between the aryl ketone and the active form of the catalyst, 2 [6]. The stable catalyst precursor 1 is transformed to the active catalyst, 2, through the loss of HCl. Treatment with 2-propanol forms ruthenium hydride 3 as a single diastereomer. Complexation of an aryl ketone precedes the hydride transfer step, which results in the reduced product. The mild reaction conditions make this catalyst an excellent candidate for incorporation in an imprinted network. The reported enantiometric excesses (ee s, +90%) serve as a useful benchmark to evaluate the influence of the imprinted polymer on the reduction. To the extent that the ruthenium center is situated in an imprinted cavity, the MIP can influence the approach of the ketone to the metal ion or better accommodate a specific reduction product. 

In 1998, Buchwald and coworkers reported the first example of the direct catalytic asymmetric a-arylation of ketone enolates using (S)-BINAP/Pd2(dba)3 as the catalyst [54]. Since then, the transition-metal-catalyzed enantioselective a-arylation of carbonyl compoimds has emerged as a simple and robust method for the construction of chiral benzylic quaternary centers [55]. 

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