|
|
 |
| » Home » Membership » Awards » List of past recipients » CSJ Award » Miyaura
|
|
|
 |
Metal-Catalyzed Bond-Forming Reactions of Organoboronic Acids
Until recently, organoboronic acids had limited use in organic synthesis due to their low reactivity for ionic and radical reactions. Over the past three decades, however, it has become increasingly clear that they are valuable reagents capable of undergoing many catalytic carbon-carbon bond formations in organic syntheses. Professor Norio Miyaura has carried out many pioneering works in the field of metal-catalyzed bond-forming reactions of boron compounds. His achievements include cross-coupling reactions and conjugate addition reactions of organoboronic acids for C-C bond-forming reactions as well as addition and coupling reactions of diborons and boranes for the syntheses of organoboronic acids and esters via B-C bond-forming reactions.
| |
Prof. Norio Miyaura
Hokkaido University
|
|
Many organometallic and nonmetallic reagents are now available for similar metal-catalyzed reactions, but much attention has recently been focused on the use of organoboronic acids in laboratories and industries since they are convenient reagents, generally thermally stable, and inert to water and oxygen, and it is easy to remove the inorganic byproducts from the reaction mixture, making the reactions suitable for industrial processes.
His representative works are summarized as follows:
1. Cross-Coupling Reactions
In 1979, Dr. Miyaura found that cross-coupling reactions of boronic acids proceed smoothly via transmetalation to palladium(II) halides in the presence of an aqueous base, a reaction that is referred to as the Suzuki coupling reaction. This protocol has been proved to be a general and powerful reaction for a wide range of selective carbon-carbon bond formations. Various bioactive compounds, including leukotriene B4 (F. Sato), DiHETE (Nicolaou), chlorothricolide (Roush), rutamycin B (Evans), PGE1 (Johnson), epothilone (Danishefsky), gambierol (M. Sasaki) and palytoxin (Kishi), have been successfully synthesized by this protocol. On the other hand, the coupling reaction of arylboronic acids greatly simplified the syntheses of biaryls and polyaryls, including pharmaceutically interesting compounds such as dynemicin A (Myers) and vancomycin (Boger), porphyrin derivatives, dendorimers, liquid crystalline compounds and LEDs. The mixed Ullman reaction is still commonplace in the literature; however, the cross-coupling reactions of arylboronic acids with aryl electrophiles appear to be productive and provide reliable results in synthesis of unsymmetrical biaryls. The highly efficient, convergent approach has overcome many of the drawbacks associated with previously reported syntheses, thus providing a method for industrial-scale preparation of the drug substance losartan (Merck), the fungicide boscalid (BASF) and liquid crystals (Merck).
2. Rhodium or Palladium-Catalyzed Conjugate Addition Reactions
Transmetalation between organometallic reagents and transition metals is a fundamental process involved in various metal-catalyzed C-C bond-forming reactions. It is the first step in metal-catalyzed 1,4-addition of organic electrophiles to electron-deficient alkenes and the second step in the palladium- or nickel-catalyzed cross-coupling reactions of organoboron compounds with carbon nucleophiles. In this field, Dr. Miyaura developed a certain new catalytic cycle starting from transmetalation to give an aryl- or 1-alkenylrhodium(I) intermediate for 1,4-addition of aryl- or 1-alkenylboronic acids to α,β-unsaturated carbonyl compounds, which has been proved to be a quite general cycle allowing various addition and coupling reactions of organometallic and -nonmetallic compounds. This discovery in 1997 was followed by the discovery of rhodium(I)-catalyzed Grignard-type addition of ArB(OH)2 to aldehydes in 1998 and the discovery of palladium-catalyzed 1,4-addition reactions of ArB(OH)2, [ArBF3]K, ArSi(OMe)3, ArSiF3 and Ar3Bi to enones in 2003. Since the reaction yields a stereogenic center at the ?-carbon, his efforts were then devoted to asymmetric syntheses using chiral rhodium or palladium(2+) catalysts. In 1998, a rhodium(I)-binap catalyst was first introduced in enantioselective 1,4-addition of aryl- and 1-alkenylboronic acids to cyclic and acyclic enones. This research led to a new chiral ligand of bidentate bisphosphoramidite (Me-BIPAM) which resulted in high enantioselectivities for both cyclic and acyclic enones. For the corresponding palladium-catalyzed reactions of organoboron, -silicon and -bismuth compounds, chiraphos and dipamp were found to result in high yields and high enantioselectivities.
3. Reactions for the Synthesis of Organoboronic Acid Derivatives
Dr. Miyaura's research on metal-catalyzed B-C bond-forming reactions for the syntheses of organoboronic acids and esters greatly contributed to recent advances in organoborane chemistry and organic syntheses using organoboranes. Hydroboration of alkynes or alkenes and transmetalation between B(OR)3 and RMgX or RLi are traditional methods for preparing organoboron compounds; however, metal-catalyzed protocol greatly simplified the methods significantly. In 1995, he discovered that (pinacolato)diboron (B2pin2) could be coupled with organic halides or triflates in the presence of a Pd catalyst to afford organoboronic esters. Direct C-H borylation of arenes with B2pin2 or pinacolborane with an iridium-bpy catalyst reported in 2002 allowed large-scale preparation of arylboronic acids from low-cost hydrocarbons. The use of metal-catalyzed addition reactions of diborons and pinacolborane resulted in various successful syntheses of 1-alkenylboronates and allylic boronates, which are important reagents for cross-coupling reactions and other metal-catalyzed bond-forming reactions. He first succeeded in cis-diboration of alkynes with B2pin2 to afford cis-1,2-(bisboryl)alkenes in the presence of a Pt(0) catalyst. A simple method for preparation of cis-1-alkenylboronates was achieved by hydroboration of terminal alkynes catalyzed by a rhodium/triisopropylphosphine complex via a novel catalytic cycle that involves a rhodium-vinylidene intermediate. For the synthesis of allylic boron compounds, cross-coupling reaction of Knochel's IZnCH2Bpin with 1-halo-1-alkenes, cross-coupling reaction of allyl acetates with B2pin2, metathesis reaction between a pinacol allylboronate and alkenes, and regioselective rhodium-catalyzed hydroboration of allenes have been developed as simple methods for preparation of allylboronates, which are valuable reagents for diastereoselective allylboration of carbonyl compounds.
In conclusion, professor Miyaura has carried out the creative works in a field of organic syntheses on the basis of catalysis and organoboron chemistry. For his achievements as well as his internationally high reputation, he was recognized as a recipient of the Japan Chemical Society Award.
|
|
 |
|
