Hayashi-Miyaura reaction

Figure 5.2 Different ligand types applied successfully in the Hayashi-Miyaura reaction.

P-Chirogenic biphosphane ligands also proved their efficiency in the catalytic Hayashi-Miyaura reaction. Imamoto and coworkers [31] were the pioneers in the application of these ligands in this... 

Figure 5.8 Monodentate phosphorous ligands used in Hayashi-Miyaura reaction as reported by luliano and coworkers [32].

Liao and coworkers [49], in 2011, reported the synthesis of a new family of benzene-based chiral hetero-disulfoxide ligands and applied them successfully in the Rh-catalyzed asymmetric 1,4-addition of arylboronic adds to chromenones. The application of the Hayashi-Miyaura reaction on these substrate types is without a doubt a milestone in the development of this process, as the synthesis of enantiopure flavanones is a significantly challenging undertaking. With this procedure, the authors achieved the desired addition products in up to 70% yield and up to 95% ee (Scheme 5.12). 

Pd- and Rh-catalyzed conjugate additions of arylboronic acids to enones and nitrostyrenes (Hayashi-Miyaura reaction)... 

As with most mechanistic investigations, the starting point is the consideration of possible working models using elementary steps that have precedent in other reactions. Based on the addition of cuprates to enones, Hayashi, Miyaura and co-workers had proposed a Rh-phenyl species (2) and an O-bound Rh enolate (3) as possible intermediates in the Rh-catalysed phenylation reaction [2], Scheme 12.2. They then developed independent syntheses of these intermediates, or close analogues. 

The first example of asymmetric rhodium-catalyzed 1,4-addition of organoboron reagents to enones was described in 1998 by Hayashi and Miyaura. Significant progress has been made in the past few years. This asymmetric addition reaction can be carried out in aqueous solvent for a broad range of substrates, such as a,/ -unsaturated ketones, esters, amides, phosphonates, nitroalkenes. The enantioselectivity is always very high (in most cases over 90% ee). This asymmetric transformation provides the best method for the enantioselective introduction of aryl and alkenyl groups to the / -position of these electron-deficient olefins. 

In 1997, Miyaura and co-workers reported the nonasymmetric version of 1,4-addition of aryl- and alkenylboronic acids to a,/ -unsaturated ketones using rhodium-phosphine complex as the catalyst.97 Later, Hayashi and Miyaura realized the asymmetric 1,4-addition with high catalytic activity and enantioselectivity.98 In the presence of ( y)-BINAP, the reaction of 2-cyclohexenone with 2.5 equiv. of phenylboronic acid gave (A)-3-phenylcyclohexanone with 97% ee (BINAP = 2,2 -bis (diphenylphosphino)-l,l -binaphthyl Scheme 29).99... 

Addition of Organometallic Reagents to Enones in Aqueous Media Rhodium-catalyzed 1,4-addition of organometallic reagents to a,p-unsaturated compounds was first developed by Miyaura in 1997. Thus, Rh(acac)(CO)2/dppb was found to catalyze the 1,4-addition of aryl- and alkenylboronic acids to several ot,(3-unsaturated ketones in water-containing solvents at 50°C. The reaction conditions were successfully modified for the development of an asymmetric variant of this process by Hayashi and Miyaura in 1998. The important points of modification are (1) the use of Rh(acac)(C2H4)2/(5)-binap as a catalyst and... 

Following the initial work by Hayashi and Miyaura using (5)-binap, several other chiral ligands were reported to achieve high enantioselectivity in the rhodium-catalyzed asymmetric 1,4-addition of arylboronic acids to ot,p-enones (Figure 3.18). A polymer-supported (X)-binap analog 42 was also synthesized and it was successfully utilized in the rhodium-catalyzed asymmetric 1,4-addition reactions in water (Figure 3.19)." The stereoselectivities observed in this system are comparable to those obtained in the unsupported Rh/(5)-binap system. It was also... 

Rhodium-catalyzed asymmetric conjugate addition has enjoyed uninterrupted prosperity since the first report by Hayashi and Miyaura [6]. Its high enantioselectivity and wide applicability are truly remarkable. However, some problems still remain, since the carbon atoms that can be successfully introduced by this rhodium-catalyzed reaction have been limited to sp carbons and the substrates employed have been limited mostly to the electron-deficient olefins free from sterically bulky substituents at a- and / -positions. These issues will be the subject of increasing attention in the future. 

Hayashi K, Kim S, Kono Y, Tamura M, Chiba K (2006) Microwave-promoted Suzuld-Miyaura coupling reactions in a cycloalkane-based thermomorphic biphasic... 

Rhodium catalysts have been widely used for C-C bond formation processes [71], Particularly noteworthy are the Rh(I)-catalyzed additions of boronic acids and their derivatives to a.p-unsaturated carbonyl compounds [72-78] and aldehydes [75, 79] (Chapter 4). The groups of Miyaura and Hayashi have shown that Rh(I) catalyzes the addition of sodium tetraphenylborate and arylstannanes to N-sulfonylimines [80-82]. Miyaura and co-workers have also reported the first example of a Rh(I)-cat-alyzed addition of an arylboronic acid to an N-sulfonylimine (77), to give sulfonamide 78 (Equation 13) [83]. Reactions proceeded with 2 equivalents of arylboronic acids using either a cationic Rh(I) catalyst alone, or in combination with appropriate phosphine ligands such as bis(diphenylphosphino)propane or P(i-Pr)3. Boronic esters will also react, particularly in the presence of triethylamine. The reaction does not proceed with simple aldimines, such as PhCH NPh. 

Hayashi and Miyaura pioneered the enantioselective rhodium-catalyzed conjugate addition of arylboronic acids to a variety of Michael acceptors a,P-unsaturated ketones, esters, lactones, amides, and lactams [215]. Generally, water is used as a cosolvent and plays a key role in the catalytic cycle, illustrated in Scheme 5.111 (cycle A) for the conjugate addition of phenylboronic acid to cyclohexenone that, when catalyzed by the Rh(I)-(S)-BINAP complex, leads to 3-phenylcyclohexanone in 97% ee and 93% chemical yield [205a]. The key intermediates of the catalytic cycle, the hydroxorhodium complex 433, the phenylrhodium complex 434, and -bound rhodium enolate 435 were characterized by NMR spectroscopy. The reaction of the hydrorhodium complex 433 with phenylboronic acid leads to a transmetallation to give the phenylrhodium complex 434. Then, the insertion of the carbon-carbon double bond of cyclohexenone into the phenylrhodium bond leads to the formation of the... 

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