Highly Selective 1,6‐Addition of Aryl Boronic Acids to α,β,γ,δ‐Unsaturated Carbonyl Compounds Catalyzed by an Iridium Complex

Abstract

The transition-metal-catalyzed 1,4-addition of organometallic reagents to electron-deficient olefins is one of the most reliable methods for selective C À C bond formation, [1] but, on the contrary, there is considerable difficulty in controlling the regioselectivity of the addition to extended conjugate systems; for example, 1,6-or 1,4-addition to electron-deficient dienes (Scheme 1). In this field of research, in which copper salts have been mainly used as the active catalysts, [1e, 2] Fukuhara and Urabe recently reported notable 1,6-selectivity with iron as a catalyst in the addition of aryl Grignard reagents to 2,4-dienoates and -dienamides.[3] Although rhodium-catalyzed conjugate addition has been developing very rapidly, [4] only a few reports have appeared that describe 1,6-or 1,4-selectivity in the addition to electron-deficient dienes. [5,6] High 1,6-selectivity in the rhodium-catalyzed reactions has been reported for a limited combination of substrates: Examples include the addition of aryl zinc reagents to dienones with b-substituents [5] and the addition of aryl and alkenyl boronic acids to d-unsubstituted dienoates.[6] Herein, we report perfect 1,6-selectivity in the addition of aryl boronic acids to a standard type of a,b,g,dunsaturated carbonyl compound, realized by use of an iridium complex as a catalyst.During our efforts to realize the 1,6-addition of aryl boronic acids to a,b,g,d-unsaturated carbonyl compounds, we found that an iridium complex, [{Ir(OH)(cod)} 2 ] (cod = cyclooctadiene), [7] efficiently catalyzes the addition to simple dienones with perfect 1,6-regioselectivity. Thus, treatment of (3E,5E)-3,5-heptadien-2-one (1) with phenylboroxine (1.0 equiv) [8] in the presence of a catalytic amount of [{Ir(OH)(cod)} 2 ] (5 mol % Ir) and H 2 O (0.5 equiv relative to B) in toluene at 80 8C for 3 h gave a mixture of 1,6-adducts, 6-phenylhepten-2-ones 2, [5] in 88 % yield (Scheme 2). The mixture consists of (Z)-6-phenyl-4-hepten-2-one (2 a) as the major isomer (93 %), its E isomer 2 b (2 %), and conjugate ketone 2 c (5 %). The formation of the 1,4-addition product 3 was not detected at all under the present reaction conditions. The formation of a small amount of diphenylation product 4 (2 %), probably formed by the 1,4-addition of phenylboronic acid to the conjugate ketone 2 c, was also observed. Although rhodium catalysts have been often used for the addition of aryl metal reagents to electron-deficient alkenes, [4] the iridium catalyst system employed in this addition has not been well demonstrated so far. As a related reaction, Mori and co-workers reported the first example of the iridiumcatalyzed addition/elimination reaction of aryl silicon reagents with acrylates to give Mizoroki-Heck-type products.[9] To the best of our knowledge, the present 1,6-addition is the first example of an iridium-catalyzed addition of aryl boronic acids to electron-deficient alkenes or dienes.[10] The unique 1,6-selectivity observed in the iridium-catalyzed addition is made clear by comparison with the result ...

Iridium‐Catalyzed Arylative Cyclization of Alkynones by 1,4‐Iridium Migration

“…First, an aryliridium species 12 is generated by transmetalation from the arylboronic acid to the iridium butoxide 11 (or alternatively, an iridium fluoride). Migratory insertion of the alkyne into 12 then occurs to give alkenyliridium species 13, [13,14] which then undergoes 1,4-migration. The resulting aryliridium intermediate 14 then undergoes nucleophilic attack onto one of the ketones to give iridium alkoxide 15.…”