Suzuki miyaara coupling of simple ketones via C-C bond activation without tension

In modern organic synthesis chemistry, transition metal catalyzed cross coupling reaction has a profound influence on bond breaking strategy Suzuki miyaara coupling (SMC) between organoborane and carbon electrophilic is one of the most commonly used reactions in the synthesis of drugs, pesticides and materials The success of this kind of reaction is largely attributed to the extensive practicability, good stability and excellent reactivity of borane reagents Classical SMC reactions use organic halides or pseudo halides as electrophilics (Fig 1a) Considering the importance of such transformations, researchers have been trying to expand the scope of electrophilics For example, nickel catalyzes the C-O bond activation of aryl ether, phenol and ester to make them the electrophilic of SMC; metal mediated C-N bond activation realizes the SMC reaction of arylamide, ammonium salt and nitro compound In addition to the polarity of C-X (x is a halogen atom), C-O and C-N bonds, SMC reactions by activating C-C bonds with small polarity and no tension are also very valuable, but such reactions are still a challenge Figure 1 The development of Suzuki miyaara coupling (SMC) reaction (source: J am Chem SOC.) recently, the research group of guangbin Dong from the University of Chicago, USA The Suzuki miyaara cross coupling reaction between simple ketones and arylboric acid derivatives catalyzed by rhodium is reported It is assumed that the reaction undergoes the processes of transfer metallization, imine oriented C-C bond activation and reduction elimination / protonation Relevant papers were published in J am Chem SOC (DOI: 10.1021 / JACS 8b02462) The first author was Dr Ying Xia At the beginning of the study, cyclopentanone 1A was used as the model substrate to couple with arylborate 1B (Fig 2) After extensive screening, the optimal reaction conditions were obtained: the catalytic system was composed of 6 mol% [Rh (C 2H 4) 2Cl] 2, 14 mol% me imes, 20 mol% TsOH · H 2O, 45 mol% 2-amino-3-methylpyridine (C1) and 25 mol% ethyl butenoate; the proton source and solvent were 2 equivalent H 2O and methf, respectively A series of control experiments confirmed the importance of each component in the reaction conditions Figure 2 Optimization of reaction conditions (source: J am Chem SOC.) after determining the optimal reaction conditions, the author expanded the range of substrate applicability of this kind of ketone mediated SMC reaction (Figure 3) The first to be studied is aryl borates (Fig 3a) For monosubstituted arylborates, the reaction activity of the electron rich substrate is better than that of the electron deficient substrate The reason may be that the transfer metallization process of the electron rich substrate is faster; the para and meta substituent substrates can react smoothly, while the ortho substituent substrate is difficult due to the potential resistance in the metallization process A series of functional groups are compatible with such cross coupling reaction conditions, including trimethylsilyl (TMS), aryl chlorine, aryl fluorine, methyl ether and phenol hydroxyl group Cyclobutane can also be kept intact in the reaction In addition, disubstituted and trisubstituted arylborates can also react to form target products Figure 3 Substrate development (source: J am Chem SOC.) next, the author studied the reactivity of ketone substrates For cyclopentanone substrate (Fig 3b), although C1 − C2 and C1 − C5 bonds may be activated in the reaction process, the reason why the reaction site tends to choose the side with larger steric hindrance is not clear; although the steric hindrance of substituents improves the selectivity of the reaction, it reduces the yield of the reaction For the 1-indanone substrate (Fig 3C), the bond breaking / coupling process takes place on the C − C bond between the aryl carbon and the carbonyl carbon, resulting in dihydrochalcone derivatives; moreover, the electron deficient 1-indanone is more reactive than the electron rich 1-indanone The noncyclic ketone substrate can also be coupled with arylborates (Fig 3D) Acetophenone reaction can produce aryl exchange products, the selectivity and reactivity of which are similar to 1-indanone substrate; acetone and asymmetric fatty ketone are also feasible substrates, but the yield of products is low In addition, the application of such coupling reactions in derivatization of natural steroids and gram scale synthesis was also studied Finally, the author has proved that the oxidative addition of Rh (I) species is involved in the process of C − C bond breaking through a comparative experiment (Fig 4) Figure 4 Control experiment (source: J am Chem SOC.) Summary: Dong guangbin's group realized Suzuki Miyaura coupling reaction of simple ketones and arylborates by rhodium catalyzed C − C bond activation Although the reaction efficiency is still to be improved, a wide range of substrate applications lay the foundation for its future application Corresponding author: Professor Dong guangbin