Radicals and Catalysis

　CO is a cheap feedstock produced from coal and steam and the development of the methods to convert CO2 to more reactive CO is actively being pursued. Powerful methodologies for the incorporation of CO into organic molecules (carbonylation) have been among long-standing themes., as seen in the History Table taken from Xiao-Feng Wu's recent review. Some of the carbonylation processes met with industrial success, which include acetic acid synthesis from MeOH and CO by Rh and Ir catalyst (Monsanto/Cativa process) and hydroformylation of alkenes by CO and molecular hydrogen (oxo process). In this important area, we strongly focused on radical carbonylation, which had been neglected for many years plagued by the low yield reactions reported in the earlier stage.
The Ryu group has pioneered the field of radical carbonylation, where acyl radicals as key intermediates. Radical carbonylation accommodates cascade reactions to couple with alkenes, alkynes, and nitrogen-containing compounds in a single operation. Thus far, we have successfully developed a variety of methods to incorporate CO into organic molecules as a carbonyl function. The concept and examples are summarized in the following two Schemes.

　Some new progresses are also highlighted. The first reaction is carbonylative bromoallylation, in which the radical arising from bromine radical addition leads to the key alkyl radical via beta-scission. The second is a formal [2+2+1] cycloaddition, in which tributyltin radical mediates the multi-step reactions as a catalyst. The third example is a radical/Pd hybrid carbonylation leading to alkyl aryl ketones, in which radical persistent effects by PdX radical works as the key. Now we are working on electron transfer carbonylation, for which neither radical mediator nor metal catalyst is necessary (the fourth example). Based on the general concept of the electron as a catalyst, advocated by Studer, Curran, and Shirakawa, we are keen to develop novel radical cascade reactions.

　Catalysis continuously stays as important challenges in chemical science no matter what catalytic species are chosen . We have found that ruthenium hydride complexes serve as an efficient catalyst for atom-economical cross-coupling reactions. The following examples show the catalytic synthesis of β-diketones and β,γ-unsaturated ketones. Since RuH causes alkene isomerization, the combined isomerization/cross-coupling sequence is possible. The other important feature of RuH catalysis is to catalyze facile transfer hydrogenation from alcohols. The following Scheme summarizes our achievements in this area. We are preparing a mini-review on this topic shortly.

　We are also very keen to the use of photocatalyst (PC). Site-selective C(sp3)-H functionalization is a holy grail in modern organic synthesis and we believe an excellent potential of radical substitution (SH2) reactions. The Barton nitrite reaction, enabling remote functionalization of saturated alcohols has a long history. The driving force is to form strong O-H bond (>105 kcal/mol) at the cost of weaker C-H bond cleavage (up to 100 kcal/mol). Intramolecularity by entropy factor is a key for site-selective delta-C-H cleavage.